Systems and methods for transdermal drug delivery and monitoring

Abstract

The present disclosure provides transdermal drug delivery systems, methods, and platforms. In one example, the smart patch includes a drug-containing layer, a communication interface, and one or more sensors configured to detect a status change of the smart patch to the smart patch, the status change of the smart patch including one or more of removing a packaging from the smart patch and applying the smart patch to skin of the patient. The smart patch further includes a processor communicatively coupled to the one or more sensors and the communication interface, wherein the processor is configured to perform operations including automatically transiting between a plurality of working conditions based on the status change of the smart patch, the plurality of working conditions of the smart patch comprising a hibernation mode, a sleep mode, and a work mode and transmitting smart patch usage data via the communication interface.

Description

WSGR Attorney Docket No. 65297-702.601SYSTEMS AND METHODS FOR TRANSDERMAL DRUG DELIVERY AND MONITORINGCROSS-REFERENCE

[0001] This application claims the benefit of U.S. Provisional Application No. 63 / 725,327, filed November 26, 2024, which is hereby incorporated by reference in its entirety.BACKGROUND

[0002] Non-compliance with drug treatment is widespread. When patients are given medications by their doctors, nearly half forget to take the drug or do not take it as prescribed, and most of the patients stop the treatment as soon as they are feeling better. According to Centers for Disease Control and Prevention, 33%-69% of hospitalizations are caused by drug non-compliance. The estimated annual cost of drug-related morbidity and mortality resulting from drug non-compliance is over $500 billion in the US alone.

[0003] The current methods of monitoring drug compliance include patient questionnaires, patient self-reports, pill counts, rates of prescription refills. These indirect methods at most provide evidence of the drug being dispensed but not ingested. In addition, they are easily influenced by reporting bias. Direct assessment methods include monitoring patient’s drug / metabolite levels and clinical response, which can be time-consuming and cost ineffective.

[0004] Smart wearables used in direct assessment methods often have external power requirements and power sources such as batteries that are quickly drained by signaling of the wearables to external devices. Smart wearables generally do not operate without an external power source or external processor over hours, days, weeks, or longer in an energy-efficient manner. Smart wearables are often not capable of automatic sensing and wireless communication over hours, days, weeks, months, or longer without external power requirements.SUMMARY

[0005] There are needs for an efficient and convenient approach of monitoring drug compliance of patients. Patients can adhere to drug treatment without the need of filling in questionnaires or measuring drug response at the hospital, thereby improving the efficacy of drug treatment. Health care providers and other personnel involved in processes associated with healthcare of the patient can track the patient’s drug compliance and provide interventions when necessary.WSGR Attorney Docket No. 65297-702.601

[0006] The present disclosure provides systems and methods that enable patients and health care providers to monitor drug compliance in an effective and efficient manner. The system and methods disclosed herein provide a multi-functional smart patch and uses thereof to treat a patient and to monitor drug compliance of the patient in real time.

[0007] The present disclosure provides systems and methods to increase battery life and cost- efficiency for a multi-functional smart patch. The present disclosure provides a system comprising a circuit design that maximizes power consumption efficiency for continuous monitoring use and wireless signaling capability over hours, days, weeks, months, or longer. This system allows for micro-battery use.

[0008] Provided in certain embodiments herein is a transdermal drug delivery patch (e.g., smart patch), comprising: one or more layers, the one or more layers comprising a drug and an adhesive. In some embodiments, a transdermal drug delivery patch provided herein comprises any component described herein for a patch or a smart patch. In some embodiments, the one or more layers comprises a drug-adhesive layer comprising a drug and an adhesive. In some embodiments, the drug is a GLP-1 agonist.

[0009] In some embodiments, the smart patch further comprises one or more sensors configured to detect a status change of the smart patch, the status change being selected from the group consisting of (i) removing a packaging from the smart patch, (ii) removing a liner from the smart patch, (iii) applying the smart patch to the skin of a patient, (iv) removing the smart patch from the skin of the patient, and (v) any combination thereof. In some embodiments, the smart patch is configured to detect the status changes of the smart patch, the status changes comprising (i) removing a packaging from the smart patch, (ii) removing a liner from the smart patch, (iii) applying the smart patch to the skin of a patient, and (iv) removing the smart patch from the skin of the patient.

[0010] In some embodiments, the transdermal smart patch comprises a communication interface. In some embodiments, the transdermal smart patch comprises a processor, such as a processor communicatively coupled to the one or more sensors and the communication interface. In some embodiments, the processor is configured to independently perform one or more operation selected from the group consisting of: (a) transiting between a plurality of working conditions based on the status change of the smart patch, wherein the plurality of working conditions of the smart patch comprises a hibernation mode, a sleep mode, and a work mode, (b) automatically and periodically transiting between the sleep mode and the work mode, (c) transmitting smart patch status data, using the communication interface, and (d) any combination thereof. In some embodiments, the processor is configured toWSGR Attorney Docket No. 65297-702.601 independently perform the following operations: (a) transiting between a plurality of working conditions based on the status changes of the smart patch, wherein the plurality of working conditions of the smart patch comprises a hibernation mode, a sleep mode, and a work mode,(b) automatically and periodically transiting between the sleep mode and the work mode, and(c) transmitting smart patch status data, using the communication interface.

[0011] In one embodiment, disclosed herein is a transdermal drug delivery smart patch, comprising: a drug-containing layer; a communication interface; one or more sensors configured to detect a status change of the smart patch, the status change comprising one or more of (i) removing a packaging from the smart patch, (ii) removing a liner from an adhesive layer of the smart patch, (iii) applying the smart patch to the skin of the patient, and (iv) removing the smart patch from the skin of the patient; and a processor communicatively coupled to the one or more sensors and the communication interface, the processor is configured to independently perform operations comprising: (a) automatically transiting between a plurality of working conditions based on the status change of the smart patch, the plurality of working conditions of the smart patch comprises a hibernation mode, a sleep mode, and a work mode, (b) detecting one or more dosage conditions based at least in part on the detected status change of the smart patch; and (c) transmitting smart patch status data, or the one or more dosage conditions, or both, using the communication interface.

[0012] In some embodiments, the transdermal drug delivery smart patch further comprises a memory. In some embodiments, the memory is communicatively coupled to the processor. In some embodiments, the memory is configured to receive and store information from the processor relating to the detected status changes of the transdermal drug delivery smart patch. In some embodiments, the one or more dosage conditions are detected based at least in part on the patch status data. In some embodiments, the one or more dosage conditions comprise an estimated dosage pattern relating to the patient. In some embodiments, the processor is further configured to generate the estimated dosage pattern based at least in part on a plurality of detected status changes of the transdermal drug delivery smart patch stored in the memory. In some embodiments, the processor is further configured to generate an estimation of an overdose, an underdose, a missed dose, a mistimed dose, or any combination thereof relating to the patient based on the dosage pattern data. In some embodiments, the processor is further configured to output instructions to the communication interface to transmit a notification based at least in part on the estimation of the overdose, the underdose, the missed dose, the mistimed dose, or any combination thereof.

[0013] In some embodiments, the communication interface is configured to transmit theWSGR Attorney Docket No. 65297-702.601 notification over a network to an external processor or database. In some embodiments, the notification comprises one or more of an alert notification relating to urgent care interventions, an alert notification relating to current drug dosage, a notification relating to drug dosage pattern data for the patient, a notification relating to drug dosage pattern data for a plurality of patients, or any combination thereof. In some embodiments, the external processor or database is configured to generate a dynamic notification message based at least in part on the notification transmitted by the drug delivery smart patch. In some embodiments, the external processor or database comprises one or more artificial intelligence (Al) / machine learning (ML) models, for example Large Language Models (LLMs) configured to generate the dynamic notification message. In some embodiments, the processor is further configured to receive signal connection data from the communication interface.

[0014] In some embodiments, the processor is further configured to select a connection signal from the one or more signals based at least in part on the signal connection data, information relating to power level of the communication interface, information relating to communication protocols, or any combination thereof. In some embodiments, the signal connection data comprises one or more of signal strength, signal network type, signal host identity, security of signal connection, or any combination thereof. In some embodiments, the information relating to communication protocols comprises one or more of beacon protocols, advertising protocols, security protocols, authentication protocols, data privacy protocols, compliance protocols, or any combination thereof. In some embodiments, the processor is further configured to output connection instructions to the communication interface based at least in part on the selected connection signal. In some embodiments, the communication interface is further configured to connect to the selected connection signal of the one or more signals based on the instructions received from the processor.

[0015] In another embodiment, disclosed herein is a transdermal drug delivery smart patch, comprising: a drug-containing layer, the drug-containing layer comprises a drug-in-adhesive layer; a backing layer; a liner; a power source; an electronics layer, the electronics layer comprising a flex circuit, the flex circuit comprising: (a) one or more sensors configured to detect environmental conditions around the transdermal drug delivery smart patch, (b) a communication interface, (c) a processor communicatively coupled to the one or more sensors and the communication interface, the processor is configured to independently perform operations comprising: (i) detecting a status change of the patch based at least in part on the detected environmental conditions; (ii) generating predictions relating to dosingWSGR Attorney Docket No. 65297-702.601 information based at least in part on the detected status change of the patch; and (ii) transmitting smart patch status data using the communication interface.

[0016] In some embodiments, the flex circuit layer is sealed from the environment. In some embodiments, the flex circuit layer is sealed using a non-permeable coating.

[0017] In some embodiments, one or more of the power source, the one or more sensors, the communication interface, or the processor, or any combination thereof, are additively manufactured. In some embodiments, the one or more sensors comprise one or more of light sensors, body temperature sensors, capacitance sensors, resistance sensors, or any combination thereof. In some embodiments, the processor is configured to receive data from the one or more sensors simultaneously. In some embodiments, the drug-in-adhesive layer comprises an opening configured to receive at least a portion of the electronics layer. In some embodiments, the drug-in adhesive layer opening is further configured to receive the flex circuit, the one or more sensors, or both.

[0018] In yet another embodiment, disclosed herein is a transdermal drug delivery smart patch, comprising: one or more layers, the one or more layers comprising a drug and an adhesive; a communication interface; one or more sensors configured to detect a status change of the smart patch, the status change comprising one or more of (i) removing a packaging from the smart patch, (ii) removing a liner from the smart patch, (iii) applying the smart patch to the skin of a patient, and (iv) removing the smart patch from the skin of the patient; and a processor communicatively coupled to the one or more sensors and the communication interface, the processor is configured to independently perform operations comprising: (a) transiting between a plurality of working conditions based on the status change of the smart patch, the plurality of working conditions of the smart patch comprises a hibernation mode, a sleep mode, and a work mode, (b) automatically and periodically transiting between the sleep mode and the work mode, and (c) transmitting smart patch status data, using the communication interface.

[0019] In some embodiments, the transdermal drug delivery smart patch further comprises a memory. In some embodiments, the memory is communicatively coupled to the processor. In some embodiments, the memory is configured to receive and store information from the processor relating to the patch status data of the transdermal drug delivery smart patch.

[0020] In some embodiments, the transdermal drug delivery smart patch further comprises a flex circuit, wherein the flex circuit comprises the processor. In some embodiments, the flex circuit further comprises the memory. In some embodiments, the flex circuit further comprises the communication interface. In some embodiments, the communication interfaceWSGR Attorney Docket No. 65297-702.601 is a flex antenna. In some embodiments, the flex antenna is communicatively coupled to the flex circuit.

[0021] In some embodiments, the communication interface is configured to transmit status information over a network to an external processor or database, the status information comprises a current status of the smart patch, a prior status of the smart patch, or a combination thereof.

[0022] In some embodiments, the transdermal drug delivery smart patch further comprises a power source (e.g., printed battery). In some embodiments, the power source (e.g., printed battery) is coupled to the flex circuit. In some embodiments, the flex circuit comprises a system-on-a-chip and a flex layer.

[0023] In some embodiments, the flex circuit is coated with a non-permeable coating (e.g., epoxy). In some embodiments, the flex antenna is coated with a non-permeable coating (e.g., epoxy). In some embodiments, the printed is coated with a non-permeable coating (e.g., epoxy). In some embodiments, the one or more layers comprises a first layer comprising the drug. In some embodiments, the first layer comprises the adhesive. In some embodiments, removing the liner from the smart patch comprising removing the liner from the first layer. In some embodiments, the transdermal drug delivery smart patch further comprises a release liner, the release liner is configured adjacent to the first layer.

[0024] In some embodiments, the one or more layers further comprises a second layer, the second layer comprises the adhesive. In some embodiments, removing the liner from the smart patch comprising removing the liner from the second layer. In some embodiments, the release liner is configured adjacent to the second layer. In some embodiments, the one or more layers comprise an electronic layer, the electronic layer comprising the flex antenna, the flex circuit, the power source (e.g., printed battery), or a combination thereof. In some embodiments, the one or more layers comprise an electronic layer, the electronic layer comprising the flex antenna, the flex circuit, and the power source (e.g., printed battery).

[0025] In some embodiments, the first layer is affixed to the electronic layer, or the coating thereof. In some embodiments, the first layer is affixed to the electronic layer, or the coating thereof, with a double sided adhesive. In some embodiments, the one or more layers comprises a backing layer, the backing layer comprises an adhesive side and a non-adhesive side, and the adhesive side of the backing layer is affixed to the electronic layer, or the coating thereof. In some embodiments, the first layer comprises a cut out, and at least a portion of the electronic layer is configured within the cut out of the first layer. In some embodiments, the second layer comprises a cut out, and at least a portion of the electronicWSGR Attorney Docket No. 65297-702.601 layer is configured within the cut out of the second layer.

[0026] In some embodiments, the one or more sensors comprise a light sensor, a temperature sensor, a capacitance sensor, or a combination thereof. In some embodiments, the one or more sensors comprise a light sensor, a temperature sensor, and a capacitance sensor.

[0027] In some embodiments, the electronic layer comprises a non-permeable coating (e.g., epoxy).

[0028] In some embodiments, the processor is configured to independently perform operations comprising adjusting antenna transmission power levels (e.g., automatically and / or periodically). In some embodiments, the processor is configured to independently perform operations comprising automatically determining a preferred cloud connection. In some embodiments, the processor is configured to independently perform operations comprising automatically determining antenna transmission power level and communication protocol based on a prioritized list of options. In some embodiments, the processor is configured to independently perform operations comprising authenticating cloud based connections. In some embodiments, the processor is configured to independently perform operations comprising encrypting data. In some embodiments, the processor is configured to independently perform operations comprising storing only anonymous (no patient identifiable) data. In some embodiments, the processor is configured to independently perform operations comprising determining patient adherence to dosing protocols.

[0029] In some embodiments, the drug is a GLP-1 agonist.

[0030] In some embodiments, the flex circuit is configured to support an external power supply. In some embodiments, the flex circuit comprises an internal battery. In some embodiments, the flex circuit comprises a biocompatible layer. In some embodiments, the biocompatible layer comprises a chemically inert material. In some embodiments, the chemically inert material comprises a parylene, ceramic, aluminum oxide, silicon dioxide, titanium dioxide, zirconium dioxide, or any combination thereof. In some embodiments, the flex circuit comprises one or more sectioned electronics. In some embodiments, the flex circuit comprises one or more ground planes. In some embodiments, the biocompatible layer has a thickness of about 0.01-100 pm. In some embodiments, the biocompatible layer has a thickness of about 0.01-80 pm. In some embodiments, the biocompatible layer has a thickness of about 0.01-60 pm. In some embodiments, the biocompatible layer has a thickness of about 0.01-40 pm. In some embodiments, the biocompatible layer has a thickness of about 0.01-20 pm. In some embodiments, the biocompatible layer has a thickness of about 0.01-10 pm. In some embodiments, the biocompatible layer has aWSGR Attorney Docket No. 65297-702.601 thickness of about 0.01-1 pm. In some embodiments, the biocompatible layer is configured to increase the shelf-life of the smart patch. In some embodiments, the biocompatible layer is configured to increase the shelf-life of the smart patch by 1-12 months. In some embodiments, the biocompatible layer is configured to increase the shelf-life of the smart patch by 1-10 years. In some embodiments, the biocompatible layer is configured to shield the smart patch from active pharmaceutical ingredient (API) vapors. In some embodiments, the flex circuit is made of a material comprising one or more substances present at sufficiently low levels to be compliant with the Restriction of Hazardous Substances Directive (RoHS). In some embodiments, the one or more substances comprises Lead (Pb), Mercury (Hg), Cadmium (Cd), Hexavalent Chromium (Cr VI), Polybrominated Biphenyls (PBB), Polybrominated Diphenyl Ethers (PBDE), Bis(2-ethylhexyl) phthalate (DEHP), Benzyl butyl phthalate (BBP), Dibutyl phthalate (DBP), Diisobutyl phthalate (DIBP) or any combination thereof.

[0031] Provided herein is a system. The system can comprise (a) any transdermal drug delivery smart patch described herein; and (b) an electronic display comprising a user interface. In some embodiments, the processor is configured to run a command-based engine. In some embodiments, the command-based engine is configured to control the one or more sensors. In some embodiments, the command-based engine is configured to manage connectivity with the Internet of Things or a local server. In some embodiments, the processor is configured to run a rule engine. In some embodiments, the rule engine is configured to monitor a multi-stage data ingestion pipeline. In some embodiments, the processor is configured to run a layered script engine. In some embodiments, the layered script engine is configured to dynamically select protocol sequences based on a source of information comprising a gateway status or a power state. In some embodiments, the processor is configured to run an adaptive sensor fusion engine. In some embodiments, the adaptive sensor fusion engine is configured to use time-aware, context-based logic to integrate sensor evaluation. In some embodiments, the user interface is configured to output the smart patch status data. In some embodiments, the user interface is configured to output the smart patch status data in a format comprising a medication regimen. In some embodiments, the user interface is configured to output the smart patch status data in a format comprising a smart patch replacement schedule. In some embodiments, the user interface is configured to output the smart patch status data in a format comprising an adherence record. In some embodiments, the user interface is configured to output the smart patch status data in a format comprising a visual or auditory alert of an upcoming dose, an overdose, anWSGR Attorney Docket No. 65297-702.601 underdose, a missed dose, a mistimed dose, or any combination thereof. In some embodiments, the user interface is configured to display three to seven temporal phases of drug dosing. In some embodiments, the user interface is configured to display three temporal phases of drug dosing. In some embodiments, the user interface is configured to display four temporal phases of drug dosing. In some embodiments, the user interface is configured to display five temporal phases of drug dosing. In some embodiments, the user interface is configured to display six temporal phases of drug dosing. In some embodiments, the user interface is configured to display seven temporal phases of drug dosing. In some embodiments, the three to seven temporal phases are categorized by color. In some embodiments, the user interface is configured to display a list of one or more medicines to be taken during a specific time window. In some embodiments, the user interface is configured to display a brand name or a generic name of the one or more medicines. In some embodiments, the list of one or more medicines is categorized by medical condition.

[0032] Provided herein is a method for transdermal drug delivery and monitoring in a patient in need thereof. The method can comprise (a) providing a transdermal drug delivery smart patch, comprising: (i) a drug-containing layer, wherein the drug-containing layer comprises a drug-in-adhesive layer; (ii) a backing layer; (iii) a liner; (iv) a power source; and (v) an electronics layer, wherein the electronics layer comprises a flex circuit, wherein the flex circuit comprises: a. one or more sensors configured to detect environmental conditions around the transdermal drug delivery smart patch; and b. a communication interface. The method can further comprise (b) detecting a status change of the smart patch based at least in part on the detected environmental conditions; (c) detecting one or more dosage conditions based at least in part on the detected status change of the smart patch; (d) transmitting the smart patch status data from the one or more sensors to a processor communicatively coupled to the one or more sensors using the communication interface; and (e) outputting the smart patch status data using an electronic display comprising a user interface, wherein the user interface is configured to display a medication regimen, a smart patch replacement schedule, or an adherence record. In some embodiments, the flex layer is sealed from the environment. In some embodiments, the flex layer is sealed using a non-permeable coating. In some embodiments, one or more of the power source, the one or more sensors, the communication interface, or the processor, or any combination thereof, are additively manufactured. In some embodiments, the one or more sensors comprise one or more of light sensors, body temperature sensors, capacitance sensors, resistance sensors, or any combination thereof. In some embodiments, the processor is configured to receive data from the one or more sensorsWSGR Attorney Docket No. 65297-702.601 simultaneously. In some embodiments, the drug-in-adhesive layer comprises an opening configured to receive at least a portion of the electronics layer. In some embodiments, the drug-in adhesive layer opening is further configured to receive the flex circuit, the one or more sensors, or both.

[0033] Provided herein is a method for transdermal drug delivery and monitoring in a patient in need thereof. The method can comprise (a) providing a transdermal drug delivery smart patch, comprising: (i) a drug-containing layer; (ii) a communication interface; and (iii) one or more sensors configured to detect a status change of the smart patch, the status change comprising one or more of a. removing a packaging from the smart patch; b. removing a liner from an adhesive layer of the smart patch; c. applying the smart patch to the skin of the patient; and d. removing the smart patch from the skin of the patient; and (iv) a processor communicatively coupled to the one or more sensors and the communication interface. The method can further comprise (b) detecting the status change of the smart patch; (c) detecting one or more dosage conditions based at least in part on the detected status change of the smart patch; (d) transmitting smart patch status data, or the one or more dosage conditions, or both, to the processor using the communication interface; and (e) outputting the information using an electronic display comprising a user interface, wherein the user interface is configured to display a medication regimen, a smart patch replacement schedule, or an adherence record. In some embodiments, the smart patch further comprises a memory. In some embodiments, the memory is communicatively coupled to the processor. In some embodiments, the memory is configured to receive and store information from the processor relating to the detected status change of the smart patch. In some embodiments, the one or more dosage conditions comprise an estimated dosage pattern relating to the patient. In some embodiments, the processor is further configured to generate the estimated dosage pattern based at least in part on a plurality of detected status changes of the transdermal drug delivery smart patch stored in the memory. In some embodiments, the processor is further configured to generate an estimation of an overdose, an underdose, a missed dose, a mistimed dose, or any combination thereof relating to the patient based on the dosage pattern data. In some embodiments, the processor is further configured to output instructions to the communication interface to transmit a notification based at least in part on the estimation of the overdose, the underdose, the missed dose, the mistimed dose, or any combination thereof. In some embodiments, the communication interface is configured to transmit the notification over a network to an external processor or database. In some embodiments, the notification comprises one or more of an alert notification relating to urgent care interventions, an alertWSGR Attorney Docket No. 65297-702.601 notification relating to current drug dosage, a notification relating to drug dosage pattern data for the patient, a notification relating to drug dosage pattern data for a plurality of patients, or any combination thereof. In some embodiments, the external processor or database generates a dynamic notification message based at least in part on the notification transmitted by the drug delivery smart patch. In some embodiments, the external processor or database comprises one or more artificial intelligence (Al) / machine learning (ML) models, for example Large Language Models (LLMs) configured to generate the dynamic notification message. In some embodiments, the processor is further configured to receive signal connection data from the communication interface. In some embodiments, the processor is further configured to select a connection signal from the one or more signals based at least in part on the signal connection data, information relating to power level of the communication interface, information relating to communication protocols, or any combination thereof. In some embodiments, the signal connection data comprises one or more of signal strength, signal network type, signal host identity, security of signal connection, or any combination thereof. In some embodiments, the information relating to communication protocols comprises one or more of beacon protocols, advertising protocols, security protocols, authentication protocols, data privacy protocols, compliance protocols, or any combination thereof. In some embodiments, the processor is further configured to output connection instructions to the communication interface based at least in part on the selected connection signal. In some embodiments, the communication interface is further configured to connect to the selected connection signal of the one or more signals based on the instructions received from the processor. In some embodiments, the smart patch further comprises a flex circuit, and wherein the flex circuit comprises the processor. In some embodiments, the flex circuit further comprises the memory. In some embodiments, the flex circuit further comprises the communication interface. In some embodiments, the communication interface is a flex antenna. In some embodiments, the flex antenna is communicatively coupled to the flex circuit. In some embodiments, the communication interface is configured to transmit status information over a network to an external processor or database, wherein the status information comprises a current status of the smart patch, a prior status of the smart patch, or a combination thereof. In some embodiments, the smart patch further comprises a power source (e.g., printed battery). In some embodiments, the power source (e.g., printed battery) is coupled to the flex circuit. In some embodiments, the flex circuit comprises a system-on-a- chip and a flex layer. In some embodiments, the flex circuit is coated with a non-permeable coating (e.g., epoxy). In some embodiments, the flex antenna is coated with a non-permeableWSGR Attorney Docket No. 65297-702.601 coating (e.g., epoxy). In some embodiments, the power source is coated with a non- permeable coating (e.g., epoxy). In some embodiments, the smart patch comprises one or more layers, wherein the one or more layers comprise a first layer comprising the drug. In some embodiments, the first layer comprises an adhesive. In some embodiments, removing the liner from the smart patch comprises removing the liner from the first layer. In some embodiments, the smart patch further comprises a release liner. In some embodiments, the release liner is configured adjacent to the first layer. In some embodiments, the one or more layers further comprises a second layer. In some embodiments, the second layer comprises the adhesive. In some embodiments, removing the liner from the smart patch comprises removing the liner from the second layer. In some embodiments, the release liner is configured adjacent to the second layer. In some embodiments, the one or more layers comprise an electronic layer, the electronic layer comprising the flex antenna, the flex circuit, the power source (e.g., printed battery), or a combination thereof. In some embodiments, the one or more layers comprise an electronic layer, the electronic layer comprising the flex antenna, the flex circuit, and the power source (e.g., printed battery). In some embodiments, the first layer is affixed to the electronic layer, or the coating thereof. In some embodiments, the first layer is affixed to the electronic layer, or the coating thereof, with a double sided adhesive. In some embodiments, the one or more layers comprises a backing layer, wherein the backing layer comprises an adhesive side and a non-adhesive side, and the adhesive side of the backing layer is affixed to the electronic layer, or the coating thereof. In some embodiments, the first layer comprises a cutout, and wherein at least a portion of the electronic layer is configured within the cutout of the first layer. In some embodiments, the second layer comprises a cut out, and wherein at least a portion of the electronic layer is configured within the cut out of the second layer. In some embodiments, the one or more sensors comprise a light sensor, a temperature sensor, a capacitance sensor, or a combination thereof. In some embodiments, the one or more sensors comprise a light sensor, a temperature sensor, and a capacitance sensor. In some embodiments, the electronic layer comprises a non-permeable coating (e.g., epoxy). In some embodiments, the processor is configured to independently perform operations comprising adjusting antenna transmission power levels (e.g., automatically and / or periodically). In some embodiments, the processor is configured to independently perform operations comprising automatically determining a preferred cloud connection. In some embodiments, the processor is configured to independently perform operations comprising automatically determining antenna transmission power level and communication protocol based on a prioritized list of options.WSGR Attorney Docket No. 65297-702.601In some embodiments, the processor is configured to independently perform operations comprising authenticating cloud based connections. In some embodiments, the processor is configured to independently perform operations comprising encrypting data. In some embodiments, the processor is configured to independently perform operations comprising storing only anonymous (no patient identifiable) data. In some embodiments, the processor is configured to independently perform operations comprising determining patient adherence to dosing protocols. In some embodiments, the drug is a GLP-1 agonist. In some embodiments, the flex circuit is configured to support an external power supply. In some embodiments, the flex circuit comprises an internal battery. In some embodiments, the flex circuit comprises a biocompatible layer. In some embodiments, the biocompatible layer comprises a chemically inert material. In some embodiments, the material comprises a parylene, ceramic, aluminum oxide, silicon dioxide, titanium dioxide, zirconium dioxide, or any combination thereof. In some embodiments, the flex circuit comprises one or more sectioned electronics. In some embodiments, the flex circuit comprises one or more ground planes. In some embodiments, the biocompatible layer has a thickness of about 0.01-100 pm. In some embodiments, the biocompatible layer has a thickness of about 0.01-80 pm. In some embodiments, the biocompatible layer has a thickness of about 0.01-60 pm. In some embodiments, the biocompatible layer has a thickness of about 0.01-40 pm. In some embodiments, the biocompatible layer has a thickness of about 0.01-20 pm. In some embodiments, the biocompatible layer has a thickness of about 0.01-10 pm. In some embodiments, the biocompatible layer has a thickness of about 0.01-1 pm. In some embodiments, the biocompatible layer is configured to increase the shelf-life of the smart patch. In some embodiments, the biocompatible layer is configured to increase the shelf-life of the smart patch by 1-12 months. In some embodiments, the biocompatible layer is configured to increase the shelf-life of the smart patch by 1-10 years. In some embodiments, the biocompatible layer is configured to shield the smart patch from active pharmaceutical ingredient (API) vapors. In some embodiments, the flex circuit is made of a material comprising one or more substances present at sufficiently low levels to be compliant with the Restriction of Hazardous Substances Directive (RoHS). In some embodiments, the one or more substances comprises Lead (Pb), Mercury (Hg), Cadmium (Cd), Hexavalent Chromium (Cr VI), Polybrominated Biphenyls (PBB), Polybrominated Diphenyl Ethers (PBDE), Bis(2- ethylhexyl) phthalate (DEHP), Benzyl butyl phthalate (BBP), Dibutyl phthalate (DBP), Diisobutyl phthalate (DIBP) or any combination thereof. In some embodiments, the method further comprises alerting the patient and / or one or more caregivers of an upcoming dose, anWSGR Attorney Docket No. 65297-702.601 overdose, an underdose, a missed dose, a mistimed dose, or any combination thereof. In some embodiments, the processor is configured to run a command-based engine. In some embodiments, the command-based engine is configured to control the one or more sensors. In some embodiments, the command-based engine is configured to manage connectivity with the Internet of Things or a local server. In some embodiments, the processor is configured to run a rule engine. In some embodiments, the rule engine is configured to monitor a multistage data ingestion pipeline. In some embodiments, the processor is configured to run a layered script engine. In some embodiments, the layered script engine is configured to dynamically select protocol sequences based on a source of information comprising a gateway status or a power state. In some embodiments, the processor is configured to run an adaptive sensor fusion engine. In some embodiments, the adaptive sensor fusion engine is configured to use time-aware, context-based logic to integrate sensor evaluation. In some embodiments, the user interface is configured to output the smart patch status data. In some embodiments, the user interface is configured to output the smart patch status data in a format comprising a medication regimen. In some embodiments, the user interface is configured to output the smart patch status data in a format comprising a smart patch replacement schedule. In some embodiments, the user interface is configured to output the smart patch status data in a format comprising an adherence record. In some embodiments, the user interface is configured to output the smart patch status data in a format comprising a visual or auditory alert of an upcoming dose, an overdose, an underdose, a missed dose, a mistimed dose, or any combination thereof. In some embodiments, the user interface is configured to display three to seven temporal phases of drug dosing. In some embodiments, the user interface is configured to display three temporal phases of drug dosing. In some embodiments, the user interface is configured to display four temporal phases of drug dosing. In some embodiments, the user interface is configured to display five temporal phases of drug dosing. In some embodiments, the user interface is configured to display six temporal phases of drug dosing. In some embodiments, the user interface is configured to display seven temporal phases of drug dosing. In some embodiments, the three to seven temporal phases are categorized by color. In some embodiments, the user interface is configured to display a list of one or more medicines to be taken during a specific time window. In some embodiments, the user interface is configured to display a brand name or a generic name of the one or more medicines. In some embodiments, the list of one or more medicines is categorized by medical condition. In some embodiments, the transmitting or the outputting occurs through a wireless communication mechanism.WSGR Attorney Docket No. 65297-702.601

[0034] Additional aspects and advantages of the present disclosure will become readily apparent to those skilled in this art from the following detailed description, wherein only illustrative embodiments of the present disclosure are shown and described. As will be realized, the present disclosure is capable of other and different embodiments, and its several details are capable of modifications in various obvious respects, all without departing from the disclosure. Accordingly, the drawings and description are to be regarded as illustrative in nature, and not as restrictive.BRIEF DESCRIPTION OF THE DRAWINGS

[0035] The novel features of the present disclosure are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present disclosure will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the present disclosure are utilized, and the accompanying drawings (also “Figure” and “FIG.” herein), of which:

[0036] FIG. 1 is a block diagram of a non-limiting example of transdermal drug delivery smart patch, according to some embodiments of the present disclosure.

[0037] FIG. 2 is a block diagram of a non-limiting example of transdermal drug delivery smart patch, according to some embodiments of the present disclosure.

[0038] FIG. 3 illustrates the structure of a non-limiting example of smart transdermal drug delivery patch comprising a layer of drug-in-adhesive, according to some embodiments of the present disclosure.

[0039] FIG. 4 illustrates the structure of a non-limiting example of smart transdermal drug delivery patch comprising a plurality of layers of drug-in-adhesive, according to some embodiments of the present disclosure.

[0040] FIG. 5 illustrates the structure of a non-limiting example of smart transdermal drug delivery patch comprising a drug reservoir, according to some embodiments of the present disclosure.

[0041] FIG. 6 illustrates the structure of a non-limiting example of smart transdermal drug delivery patch comprising a drug reservoir and an adhesive ring therearound, according to some embodiments of the present disclosure.

[0042] FIG. 7 illustrates the structure of a non-limiting example of smart transdermal drug delivery patch comprising a drug-containing microneedle array, according to some embodiments of the present disclosure.WSGR Attorney Docket No. 65297-702.601

[0043] FIG. 8 illustrates the detection of a status change of the smart patch of removing a packaging from a smart transdermal drug delivery patch using one or more sensors, according to some embodiments of the present disclosure.

[0044] FIG. 9 illustrates the detection of a status change of the smart patch of opening a smart transdermal drug delivery patch using one or more optical sensors, according to some embodiments of the present disclosure.

[0045] FIG. 10 illustrates the detection of a status change of the smart patch of removing a liner from a smart transdermal drug delivery patch using one or more sensors, according to some embodiments of the present disclosure.

[0046] FIG. 11 illustrates the detection of a status change of the smart patch of applying a smart transdermal drug delivery patch to patient skin using one or more sensors, according to some embodiments of the present disclosure.

[0047] FIG. 12 illustrates a process of treating a patient in need thereof using a transdermal drug delivery smart patch, according to some embodiments of the present disclosure.

[0048] FIG. 13 illustrates correlations between triggering events and corresponding working conditions of a transdermal drug delivery smart patch, according to some embodiments of the present disclosure.

[0049] FIG. 14 illustrates a smart transdermal drug delivery patch connected to a wireless network, according to some embodiments of the present disclosure.

[0050] FIG. 15 illustrates a non-limiting diagram of an exemplary internet connectivity system between a device layer, end user applications, and cloud-based connectivity systems.

[0051] FIG. 16 illustrates a non-limiting diagram of an exemplary technology stack of a low energy system-on-a-chip with short-range wireless signals connectivity capability.

[0052] FIG. 17 illustrates a non-limiting diagram of an exemplary internet connectivity and authentication system between one or more devices of one or more users and encryptionbased data authentication schemes.

[0053] FIG. 18 illustrates a non-limiting diagram of an exemplary connectivity configuration for electronics databases.

[0054] FIG. 19 illustrates a non-limiting diagram of an exemplary connectivity configuration for members databases.

[0055] FIG. 20 illustrates a non-limiting diagram of an exemplary connectivity configuration for integrations databases.

[0056] FIG. 21 illustrates a non-limiting diagram of an exemplary connectivity configuration for operations databases.WSGR Attorney Docket No. 65297-702.601

[0057] FIG. 22 illustrates a non-limiting diagram of an exemplary connectivity configuration for various databases.

[0058] FIG. 23 illustrates a non-limiting example of a graphic user interface (GUI), in this case, a GUI providing an introductory notification to a user.

[0059] FIG. 24 illustrates a non-limiting example of a GUI, in this case, a GUI providing a routine manager and reminder manager.

[0060] FIG. 25 illustrates a non-limiting example of a GUI, in this case, a GUI providing a routine manager.

[0061] FIG. 26 illustrates a non-limiting example of a GUI, in this case, a GUI providing a notification of a new Tech-Enabled Therapeutics (TET) smart patch detection and a routine manager.

[0062] FIG. 27 illustrates a non-limiting example of a GUI, in this case, a GUI providing a completed routine in a routine manager.

[0063] FIG. 28 illustrates a non-limiting example of a GUI, in this case, a GUI providing a notification to the user of no alerts.

[0064] FIG. 29 illustrates a non-limiting example of a GUI, in this case, a GUI providing an introductory notification to a user, and a notification of the presence of one or more alerts to the user.

[0065] FIG. 30 illustrates a non-limiting example of a GUI, in this case, a GUI providing a reminder to the user that a routine is due and a change of TET smart patch is due.

[0066] FIG. 31 illustrates a non-limiting example of a GUI, in this case, a GUI providing a second reminder to the user that a routine is due and a change of TET smart patch is due.

[0067] FIG. 32 illustrates a non-limiting example of a GUI, in this case, a GUI providing a routine manager having one or more overdue routine elements.

[0068] FIG. 33 illustrates a non-limiting example of a GUI, in this case, a GUI providing a notification alert to a designated person other than the user of one or more overdue routine elements.

[0069] FIG. 34 illustrates a non-limiting example of a GUI, in this case, a GUI providing a notification of a call from a person other than the user.

[0070] FIG. 35 illustrates a non-limiting example of a GUI, in this case, a GUI providing a notification to a person other than the user that a new TET smart patch has been detected.

[0071] FIG. 36 illustrates a non-limiting example of a GUI, in this case, a GUI providing a routine manager having all routine elements completed.WSGR Attorney Docket No. 65297-702.601

[0072] FIG. 37 illustrates a non-limiting example of a GUI, in this case, a GUI providing a notification to a person other than the user that one or more routine elements are completed.

[0073] FIG. 38 shows a non-limiting example of a computing device; in this case, a device with one or more processors, memory, storage, and a network interface, per one or more embodiments herein.

[0074] FIG. 39 shows a non-limiting example of a smart transdermal drug delivery patch comprising multiple layers.DETAILED DESCRIPTION

[0075] While various embodiments of the present disclosure have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions may occur to those skilled in the art without departing from the present disclosure. It should be understood that various alternatives to the embodiments of the present disclosure described herein may be employed.

[0076] Whenever the term “at least,” “greater than,” or “greater than or equal to” precedes the first numerical value in a series of two or more numerical values, the term “at least,” “greater than” or “greater than or equal to” applies to each of the numerical values in that series of numerical values. For example, greater than or equal to 1, 2, or 3 is equivalent to greater than or equal to 1, greater than or equal to 2, or greater than or equal to 3.

[0077] Whenever the term “no more than,” “less than,” or “less than or equal to” precedes the first numerical value in a series of two or more numerical values, the term “no more than,” “less than,” or “less than or equal to” applies to each of the numerical values in that series of numerical values. For example, less than or equal to 3, 2, or 1 is equivalent to less than or equal to 3, less than or equal to 2, or less than or equal to 1.

[0078] The term “about” or “approximately” means within an acceptable error range for the particular value as determined by one of ordinary skill in the art, which will depend in part on how the value is measured or determined, e.g., the limitations of the measurement system. For example, “about” can mean within 1 or more than 1 standard deviation, per the practice in the art. Alternatively, “about” can mean a range of up to 20%, up to 10%, up to 5%, or up to 1% of a given value. Alternatively, particularly with respect to biological systems or processes, the term can mean within an order of magnitude, preferably within 5-fold, and more preferably within 2-fold, of a value. Where particular values are described in theWSGR Attorney Docket No. 65297-702.601 application and claims, unless otherwise stated the term “about” meaning within an acceptable error range for the particular value should be assumed.

[0079] The term “and / or” used herein to link one or more species means one of the species or any combinations of the one or more species.

[0080] The term “transdermal” refers to a route of administration wherein ingredients are delivered across the skin for systemic distribution. Examples include transdermal patches used for medicine delivery. The drug is administered in the form of a smart patch or ointment that delivers the drug into the circulation for systemic effect. Transdermal administration can be accomplished by applying, pasting, rolling, attaching, pouring, pressing, rubbing, etc., of a transdermal preparation onto a skin surface.

[0081] The term “transdermal patch” refers to a matrix or liquid type of delivery device which is used to transdermally deliver doses of a substance from skin to a patient’s bloodstream, over a specific application period.

[0082] The term “transdermal smart patch,” “smart transdermal patch,” “smart transdermal smart patch,” “smart transdermal drug delivery smart patch,” “transdermal drug delivery smart patch,” and “smart transdermal drug delivery patch”, are used herein interchangeably.

[0083] The term “drug” as used herein generally refers to any substance that alters the physiology of a subject. The term “drug” may be used interchangeably herein with the terms “therapeutic agent”, “medication”, “pharmacologically active agent”, “active pharmaceutical ingredients (APIs)” and the like. It will be understood that a “drug” formulation may include more than one therapeutic agent, wherein exemplary combinations of therapeutic agents include a combination of two or more drugs.

[0084] The term “reservoir” as used herein refers to any form of mechanism to retain an element, compound, pharmaceutical composition, active agent, and the like, in a liquid state, solid state, gaseous state, mixed state and / or transitional state. Typically, a reservoir serves to retain a biologically active agent (e.g., drug) prior to the discharge of such agent into the biological interface.

[0085] The term “adhesive” refers to any non-metallic substance applied to one or both surfaces of two separate items that binds them together and resists their separation. Adhesive, also known as glue, cement, mucilage, or paste. Adhesive may be classified in a variety of ways depending on their chemistries (e.g., epoxies, polyurethanes, polyimides), forms (e.g., paste, liquid, film, pellets, tape), types (e.g., hot melt, reactive hot melt, thermosetting, pressure sensitive, contact, etc.), or load carrying capabilities (structural, semi-structural, or non-structural).WSGR Attorney Docket No. 65297-702.601

[0086] The term “processor” may be used interchangeably with terms such as “microprocessor”, “controller”, “microcontroller”, and the like. A processor may function independently and make decisions affecting control of the patch independently.

[0087] Disclosed is a smart transdermal drug delivery patch comprising a drug-containing layer, a communication interface, one or more sensors configured to detect a status change of the smart patch to the smart patch, and a processor communicatively coupled to the one or more sensors. The status change of the smart patch may comprise removing a packaging from the smart patch, applying the smart patch to the patient skin, and removing the smart patch from the patient skin. The processor may be on the smart patch and can be integrated into the smart patch. The one or more sensors may be on the smart patch and can be integrated into the smart patch. The communication interface may be on the smart patch and can be integrated into the smart patch. The processor may control the smart patch to automatically transit between the plurality of working conditions based on the detected status change of the smart patch, and transmit smart patch usage data via the communication interface.

[0088] In some embodiments, the processor being integrated onto the smart patch or otherwise present on the smart patch, and able to independently control the smart patch, can increase power efficiency and decrease power use involved with signaling even in a powerintensive mode such as work mode.

[0089] The smart transdermal drug delivery patch may have different working conditions, for example, a hibernation mode, a sleep mode, and a work mode. The smart patch may be at the hibernation mode as default after being manufactured, or when stored in a packaging (e.g., wrapped). The hibernation mode can comprise the smart patch not receiving signals and not sending signals to an external source. The sleep mode can comprise minimal or periodic sending or receiving of signals. The work mode may comprise frequent or consistent sending or receiving of signals. When a patient removes the packaging from the smart patch, the processor may control the smart patch to automatically transit from the hibernation mode to a non-hibernation mode (e.g., sleep mode and work mode). The processor may be on the smart patch and can independently control the smart patch to automatically transition from the hibernation mode to a non-hibernation mode. The processor may be on the smart patch and can independently control the smart patch to automatically transition from a non-hibernation mode (e.g., sleep mode and work mode) to the hibernation mode. The processor can independently control the smart patch to automatically transit between different working conditions without external signaling, such as external instructions. The smart patch can transition from a hibernation mode to a sleep mode. The smart patch can transition from aWSGR Attorney Docket No. 65297-702.601 hibernation mode to a work mode. The smart patch can transition from a sleep mode to a hibernation mode. The smart patch can transition from a work mode to a hibernation mode. The smart patch can transition from a sleep mode to a work mode. The smart patch can transition from a work mode to a sleep mode. The processor integrated into the smart patch can independently control the smart patch transition from a hibernation mode to a sleep mode. The processor integrated into the smart patch can independently control the smart patch transition from a sleep mode to a hibernation mode. The processor integrated into the smart patch can independently control the smart patch transition from a work mode to a hibernation mode. The processor integrated into the smart patch can independently control the smart patch transition from a hibernation mode to a work mode. The processor integrated into the smart patch can independently control the smart patch transition from a sleep mode to a work mode. The processor integrated into the smart patch can independently control the smart patch transition from a work mode to a sleep mode.

[0090] In some embodiments, the smart patch may comprise a flex circuit in electrical connection with the sensors. The flex circuit may comprise one or more conducting pads. The packaging may comprise a wrapper with one or more of conducting pads and conducting traces positioned on an inner surface of the wrapper. When the wrapper is in contact with the smart patch, the conducting pads and conducting traces on the wrapper and the conducting pads on the flex circuit may form an electrical connection. When the patient removes the wrapper, the connection may be interrupted and detected by the sensors. The processor may control the smart patch to switch working conditions based on this status change of the smart patch. In some embodiments, one or more sensors of a TET smart patch may activate in response to a package surrounding the TET smart patch or attached to the TET smart patch being manipulated or opened. In some embodiments, one or more sensors of the TET smart patch can be activated when a seal of a packaging surrounding the TET smart patch or attached to the TET smart patch is broken. In some embodiments, the TET smart patch can complete an electric circuit with a low-energy electrical current when in the packaging. In some embodiments, manipulating one or more parts of the packaging, like breaking a seal, peeling back a portion of the package, ripping or poking one or more parts of the package, or disconnecting a part of the package, for example, can activate the one or more sensors. The sensors can be, for example, light sensors, electricity sensors, pressure sensors, infrared sensors, sound sensors, ultrasound sensors, gas sensors, capacitive sensors, humidity sensors, touch sensors, temperature sensors, magnetic field sensors, resistive sensors, or any combination thereof.WSGR Attorney Docket No. 65297-702.601

[0091] When the smart patch is at the sleep mode, the processor may control the smart patch to automatically transit from the sleep mode to the work mode, upon further status change of the smart patch, including removing a liner from the smart patch, and applying the smart patch to patient skin. In some embodiments, the packaging may comprise a removable liner in contact with the drug-containing layer. The removable liner may comprise one or more of conducting pads and conducting traces. When the liner is in contact with the drug-containing layer, the conducting pads and conducting traces on the liner and the conducting pads on the flex circuit may form an electrical connection. When the patient removes the liner, the connection may be interrupted and detected by the sensors. The processor may control the smart patch to switch working conditions based on this status change of the smart patch.

[0092] In some embodiments, when the patient applies the smart patch to the skin of the patient, the conducting pads on the flex circuit and the skin may form an electrical connection, which can be detected by the sensors. The processor may control the smart patch to switch working conditions based on this status change of the smart patch. The processor may further analyze an electrodermal response between the skin and the conducting pads for clinical diagnostic data collection and monitoring. Similarly, when the patient removes the smart patch from the skin, the electrical connection between the conducting pads on the flex circuit and the skin may be interrupted and detected by the sensors. The processor may control the smart patch to switch working conditions based on this status change of the smart patch, for example, from the work mode to one of the sleep mode and hibernation mode.

[0093] In other embodiments, when the wrapper is removed, the smart patch may be switched from the hibernation mode to the work mode. The processor may control the smart patch to remain in the current working condition when the patient performs further actions, including removing the liner and applying the smart patch.

[0094] In some embodiments, the smart patch may be at the sleep mode as default during use. The sleep mode requires lower power consumption and extends the use life of the smart patch. The processor may control the smart patch to remain at the sleep mode until a sensing event (e.g., status change of the smart patch to the smart patch) occurs and is detected by the sensors, and / or the smart patch receives a communication signal via the communication interface. For example, the patient may be non-adherent to her medication and remove the smart patch early. When the smart patch is connected to a wireless network, a smart device (e.g., a mobile device, smart watch, smart speakers and displays) may receive an alert or intervention message from a cloud or other user devices (e.g., health provider devices) in the network requesting the patient for drug compliance.WSGR Attorney Docket No. 65297-702.601

[0095] In some embodiments, the battery may enter a low-power mode. In some embodiments, the battery may enter a low-power mode as a result of communication from the communication subsystem of the TET smart patch. In some embodiments, the battery may enter a low-power mode as a result of a communication from a cloud module. In some embodiments, the battery may enter a low-power mode in response to a signal from one or more sensors. In some embodiments, the battery can enter a low-power mode to preserve battery and extend battery life. In some embodiments, the battery can enter a low-power mode as a result of a signal for a change of the TET smart patch from work mode to sleep or hibernation mode. In some embodiments, the battery may exit a low-power mode. In some embodiments, the battery may exit a low-power mode as a result of communication from the communication subsystem of the TET smart patch. In some embodiments, the battery may exit a low-power mode as a result of a communication from a cloud module. In some embodiments, the battery may exit a low-power mode in response to a signal from one or more sensors. In some embodiments, the battery can exit a low-power mode to preserve battery and extend battery life. In some embodiments, the battery can exit a low-power mode as a result of a signal for a change of the TET smart patch from sleep or hibernation mode to work mode. In some embodiments, the signal for a change of the TET smart patch can be transmitted multiple times per second, once per second, multiple times per minute, once per minute, one or more times per about two minutes, one or more times per about five minutes, one or more times per about ten minutes, one or more times per about 15 minutes, one or more times per about 30 minutes, one or more times per about one hour, one or more times per about two hours, one or more times per about three hours, one or more times per about four hours, one or more times per about six hours, one or more times per about ten hours, one or more times per about twelve hours, one or more times per about 24 hours, one or more times per about 36 hours, one or more times per about 48 hours, one or more times per about one week, one or more times per about two weeks, one or more times per about one month, one or more times per about two months, one or more times per about three months, one or more times per about six months, one or more times per about twelve months, one or more times per about one year, or one or more times per about more than one year.

[0096] In other embodiments, the processor may control the smart patch to switch between the sleep mode and the work mode periodically. When the smart patch is switched to the work mode, the processor may transmit smart patch usage data, a current working condition of the smart patch, transitions of working conditions, a state of sensors, a sequence of stateWSGR Attorney Docket No. 65297-702.601 changes, date and time stamp of each state change, a unique smart patch identifier via the communication interface.

[0097] In some embodiments, after being applied to the patient skin, the smart transdermal drug delivery patch may have a use life of 1-5 hours, 1-10 hours, 1-20 hours, 1-30 hours, 1- 40 hours, 1-50 hours, 1-60 hours, 1-70 hours, 1-80 hours, 1-90 hours, 1-100 hours, 1-110 hours, 1-120 hours, 1-130 hours, 1-140 hours, 1-150 hours, 1-160 hours, or 1-170 hours.

[0098] In some embodiments, the drug-containing layer may comprise a layer of drug-inadhesive. In other embodiments, the drug-containing layer may comprise a plurality of layers of drug-in-adhesive and a membrane positioned therebetween. In other embodiments, the drug-containing layer may comprise a drug reservoir, an adhesive layer and a membrane positioned therebetween. In other embodiments, the drug-containing layer may comprise a drug-containing microneedle array and an adhesive layer. The adhesive layer may surround each of the microneedles.

[0099] In some embodiments, the drug-containing layer may comprise one or more drugs loaded thereon. In some embodiments, the drug-containing layer may also comprise one or more excipients. In some embodiments, the one or more excipients may comprise one or more chemical enhancers that facilitate the permeation of the drug through the skin and drug delivery.

[0100] In some embodiments, the smart patch may comprise one or more status LEDs controlled by the processor that provide visual indications of the current working conditions and transitions between working conditions, and potential malfunction of the smart patch.

[0101] In some embodiments, the smart patch may comprise a power supply. In some embodiments, the power supply may be a printed power supply. In some embodiments, the power supply may comprise a battery. In some embodiments, the power supply may comprise an additively manufactured power supply. In some embodiments, the power supply can comprise an additively manufactured battery. In some embodiments, the power supply can comprise a printed battery.

[0102] In some embodiments, the smart transdermal drug delivery patch processor may comprise a system-on-a-chip (SoC). In some embodiments, the SoC can comprise one or more of a messaging subsystem, a sensor subsystem, a power state subsystem, a communication state subsystem, a communication subsystem, a printable battery, or an event cache subsystem, or any combination thereof.

[0103] In some embodiments, the communication subsystem can send data to or from a cloud server system. In some embodiments, the sensor subunit can receive data from the one orWSGR Attorney Docket No. 65297-702.601 more sensors. In some cases, the one or more sensors can detect information concerning the smart patch status data.

[0104] The smart patch may comprise memory that stores smart patch usage data comprising one or more of the status changes of the smart patch, a dose of the drug, an overdose of the drug, a missed dose, an aborted dose, a timing of the dose, a frequency of doses, a current working condition of the smart patch, transitions of the working conditions of the smart patch, or any combination thereof. Additionally, the memory may store a unique smart patch identifier, a current state of each of the sensors, a sequence of state changes of the sensors, date and time stamp of each state change, or any combination thereof.

[0105] The smart patch may be connected to a wireless network. The network may be a mesh network or an Internet of Things (loT) network. The smart patch may transmit smart patch usage data to one or more devices in the network via the communication interface. In some embodiments, devices with backend applications in the network may receive patient data comprising clinical data, a geolocation, a physical activity, a motion, demographics associated with the patient. The clinical data may comprise drug prescription, an expected dosage of the drug, an expected timing of administering the drug, an electronic health record (EHR) of the patient, and physiological parameters of the patient.

[0106] In some embodiments, devices with backend applications in the network may determine the drug compliance of the patient based on the smart patch usage data and patient data. For example, the smart patch usage data may be compared with the patient’s drug prescription, an expected dosage, and / or an expected timing of administering the drug. When there is inconsistency indicating non-compliance, the devices may generate an alert, a reporting message, or an intervention message of the drug compliance, which may be transmitted to other devices in the network.

[0107] In some embodiments, the smart patch status data can be generated using a processor contained within the transdermal drug delivery smart patch to average the values of one or more sensor inputs of the smart patch. In some embodiments, drug compliance can be determined by comparing an individual value measured by the one or more sensors of the smart patch to an average value of sensor inputs of the smart patch.

[0108] During the use of the smart patch, the patient may wear other devices that collect patient data including physiological parameters, physical activities, and motions, and transmit the data to the network. Upon receiving the data, the devices with backend applications in the network may determine whether the patient has a clinical response to the drug, for example, an adverse drug reaction. The devices may generate messages to the patient device providingWSGR Attorney Docket No. 65297-702.601 guidance of handling medical emergency, and an alert to health provider’s devices such that health providers can provide further intervention.

[0109] FIG. l is a block diagram of a non-limiting example of transdermal drug delivery smart patch, according to some embodiments of the present disclosure. The smart transdermal drug delivery patch 100 comprises memory 110, one or more processors 120, communication interface 130, power supply 140, one or more status LED 150, and one or more sensors 160 that communicate with each other, and with other components, via a bus 170. All of these elements may interface directly or via one or more interfaces or adaptors to the bus 170.

[0110] The smart transdermal drug delivery patch 100 comprises one or more processor(s) 120 that carry out functions and control other components in the smart patch. The processor(s) 120 may optionally contain a cache memory unit for temporary local storage of instructions, data, or computer addresses. The processor(s) 120 may be configured to assist in execution of computer readable instructions. The smart patch 100 may provide functionality for other components depicted in FIG. 1 as a result of the processor(s) 120 executing non- transitory, processor-executable instructions embodied in one or more computer-readable storage media, such as memory 110. The computer-readable media may store software that implements particular embodiments, and the processor(s) 120 may execute the software. The memory 110 may read the software from one or more other computer-readable media or from one or more other sources through a suitable interface, such as communication interface 130. The software may cause the processor(s) 120 to carry out one or more processes or one or more steps of one or more processes described or illustrated herein. Carrying out such processes or steps may include defining data structures stored in the memory 110 and modifying the data structures as directed by the software.[oni] The memory 110 may include various components (e.g., machine readable media) including, but not limited to, a random-access memory component (e.g., RAM) (e.g., static RAM (SRAM), dynamic RAM (DRAM), ferroelectric random access memory (FRAM), phase-change random access memory (PRAM), etc.), a read-only memory component (e.g., ROM), or any combination thereof. ROM may act to communicate data and instructions unidirectionally to the processor(s) 120, and RAM may act to communicate data and instructions bidirectionally with the processor(s) 120. ROM and RAM may include any suitable tangible computer-readable media. In one example, a basic input / output system (BIOS), including basic routines that help to transfer information between elements within the smart patch 100, such as during start-up, may be stored in the memory 110.WSGR Attorney Docket No. 65297-702.601

[0112] The smart patch 100 may communicate with a network via the communication interface 130. The smart patch 100 may communicate with other devices in the network via the communication interface. The other devices may include personal devices and enterprise systems, distributed computing systems, cloud storage systems, cloud computing systems, and the like, connected to a network. In some embodiments, the other devices may comprise device(s) associated with the patient, device(s) associated with health providers / car egivers, and device(s) associated with business operators associated with healthcare of the patient, including insurance and pharmacy.

[0113] Communications to and from the smart patch 100 may be sent through the communication interface 130. The smart patch 100 may store outgoing communications (e.g., smart patch usage data, unique smart patch identifier, sensor state data) in the form of one or more packets in the memory 110 and communicated to the network from the communication interface 130. In some embodiments, the smart patch usage data may comprise status change of the smart patch, a dose of the drug, an overdose of the drug, a missed dose, an aborted dose, a timing of the dose, a frequency of doses, a current working condition of the smart patch, transitions of the working conditions of the smart patch, a malfunction of the smart patch, or any combination thereof. The processor 120 may transmit smart patch usage data to the network via the communication interface 130.

[0114] The communication interface 130 may receive incoming communications in the form of one or more packets from the network or other devices, and the smart patch 100 may store and process the incoming communications in the memory 110 for processing. In some embodiments, users (e.g., health care providers / car egivers) on the network may determine drug compliance of the patient based on the received smart patch usage data. In other embodiments, backend applications in the network may automatically determine, based on the smart patch usage data, drug compliance of the patient. When non-compliance is identified, an alert, a reporting message, or an intervention message of the drug compliance may be generated and transmitted via the network. In some embodiments, incoming communications like alerts and messages may be received on the patient’s device connected to the network, thereby notifying the non-compliance. The smart patch 100, connected to the patient’s device via a wireless network (e.g., loT), may receive communications from the patient’s device and switch working conditions, for example, from the sleep mode to work mode.

[0115] In some embodiments, the smart patch status data can be generated using a processor contained within the transdermal drug delivery smart patch to average the values of one orWSGR Attorney Docket No. 65297-702.601 more sensor inputs of the smart patch. In some embodiments, drug compliance can be determined by comparing an individual value measured by the one or more sensors of the smart patch to an average value of sensor inputs of the smart patch.

[0116] The communication interface 130 may include, but not limited to, a network interface. Examples of the network or network segment may include, but not limited to, a distributed computing system, a cloud computing system, a wide area network (WAN) (e.g., the Internet, an enterprise network), a local area network (LAN) (e.g., a network associated with an office, a building, a campus or other relatively small geographic space), a telephone network, a direct connection between two computing devices, a peer-to-peer network, and any combination thereof. The network may employ a wired and / or a wireless mode of communication. The network may be a mesh network. The network may be an loT network. In general, any network topology may be used.

[0117] In some embodiments, the communication may use a protocol selected from the group consisting of, but not limited to, short-range wireless signals, near-field communication (NFC) signals, broadband, narrow band-internet of Things (NB-IoT), radio signals, WLAN, cellular signals, and future revisions of the aforementioned protocol standards. For example, the smart patch 100 may wirelessly communicate with other devices via short-range wireless signals low energy radio (LER). In some embodiments, the communication may take place in the signal range of about 2.4GHz to about 2.5GHz.

[0118] The power supply 140 may provide power to the smart patch 100 during its use. In some embodiments, the power supply 140 may comprise a printed power supply or a thin- film power supply. The printed power supply may be printed batteries.

[0119] The smart patch 100 may comprise an output device, for example, status LED 150, controlled by the processor that provides a visual indication of the working conditions of the smart patch 100. The status LED 150 may comprise one or more LEDs. In some embodiments, the color, numbers, on / off status, blinks with different frequencies, or any combination thereof may be used to indicate the status of the smart patch 100, including whether the smart patch is functioning normally, the current working condition and transitions of working conditions.

[0120] The sensors 160 may comprise one or more sensors that are communicatively connected to the processor 120 via the bus 170. The sensors 160 may monitor status change of the smart patch to the smart patch 100. In some embodiments, the sensors 160 may comprise one or more optical sensors. When a patient removes a packaging from the smart patch 100, the optical sensors may detect the incident light change, convert it into electricalWSGR Attorney Docket No. 65297-702.601 signals and transmit to the processor 120. In some embodiments, the optical sensors can transmit the signal multiple times per second, once per second, multiple times per minute, once per minute, one or more times per about two minutes, one or more times per about five minutes, one or more times per about ten minutes, one or more times per about 15 minutes, one or more times per about 30 minutes, one or more times per about one hour, one or more times per about two hours, one or more times per about three hours, one or more times per about four hours, one or more times per about six hours, one or more times per about ten hours, one or more times per about twelve hours, one or more times per about 24 hours, one or more times per about 36 hours, one or more times per about 48 hours, one or more times per about one week, one or more times per about two weeks, one or more times per about one month, one or more times per about two months, one or more times per about three months, one or more times per about six months, one or more times per about twelve months, one or more times per about one year, or one or more times per about more than one year.

[0121] Upon receiving the signal representing the status change of the smart patch of removing the packaging, the processor 120 may automatically control the smart patch to transit between working conditions. The sensor state and the state changes which represent the given status change of the smart patch, may be stored in the memory 110.

[0122] In other embodiments, the sensors 160 may comprise electronic sensors that detect electronic signal changes caused by status change of the smart patch to the smart patch 100. For example, the sensors 160 may detect the electronic signal changes caused by patient removing a packaging from the smart patch, applying the smart patch to skin, or removing the smart patch from skin. In some embodiments, the sensors can periodically detect the electronic signal multiple times per second, once per second, multiple times per minute, once per minute, one or more times per about two minutes, one or more times per about five minutes, one or more times per about ten minutes, one or more times per about 15 minutes, one or more times per about 30 minutes, one or more times per about one hour, one or more times per about two hours, one or more times per about three hours, one or more times per about four hours, one or more times per about six hours, one or more times per about ten hours, one or more times per about twelve hours, one or more times per about 24 hours, one or more times per about 36 hours, one or more times per about 48 hours, one or more times per about one week, one or more times per about two weeks, one or more times per about one month, one or more times per about two months, one or more times per about three months, one or more times per about six months, one or more times per about twelve months, one or more times per about one year, or one or more times per about more than one year.WSGR Attorney Docket No. 65297-702.601

[0123] The sensors 160 may transmit the electrical signal change to the processors 120, which may in turn control the smart patch to transit between different working conditions based on the given status change of the smart patch. In some embodiments, the sensors can transmit the electrical signal change to the processors multiple times per second, once per second, multiple times per minute, once per minute, one or more times per about two minutes, one or more times per about five minutes, one or more times per about ten minutes, one or more times per about 15 minutes, one or more times per about 30 minutes, one or more times per about one hour, one or more times per about two hours, one or more times per about three hours, one or more times per about four hours, one or more times per about six hours, one or more times per about ten hours, one or more times per about twelve hours, one or more times per about 24 hours, one or more times per about 36 hours, one or more times per about 48 hours, one or more times per about one week, one or more times per about two weeks, one or more times per about one month, one or more times per about two months, one or more times per about three months, one or more times per about six months, one or more times per about twelve months, one or more times per about one year, or one or more times per about more than one year.

[0124] The bus 170 connects a wide variety of subsystems. Herein, reference to a bus may encompass one or more digital signal lines serving a common function, where appropriate. The Bus 170 may be any of several types of bus structures including, but not limited to, a memory bus, a memory controller, a peripheral bus, a local bus, and any combination thereof, using any of a variety of bus architectures. In some embodiments, the bus 170 may be an on- chip bus. Some of the non-limiting examples of bus architectures may comprise Advanced Microcontroller Bus Architecture (AMBA) which may include an Advanced High- performance Bus (AHB), an Advanced System Bus (ASB), and an Advanced Peripheral Bus (APB), AMBA Advanced extensible Interface (AXI) bus, a WISHBONE bus, an Open Core Protocol (OCP), a CoreConnect bus, MSBUS that comprises a master bus (MBUS) and a slave bus (SBUS), and any combination thereof.

[0125] FIG. 2 is a block diagram of a non-limiting example of smart transdermal drug delivery patch 200. The smart patch 200 comprises a flex circuit 210 comprising memory 212, a processor 214, a short-range wireless signals Low Energy Radio 216, and an input- and-output circuitry 218. The flex circuit 210 may be a system-on-chip (e.g., integrated circuit). The short-range wireless signals Low Energy Radio 216 functions as the communication interface (e.g., communication interface 130 in FIG. 1) by transmitting radioWSGR Attorney Docket No. 65297-702.601 signals and communicating with a network 270. In some embodiments, the communication may take place in the signal range of about 2.4GHz to about 2.5GHz.

[0126] In some embodiments, the short-range wireless signals Low Energy Radio can transmit radio signals multiple times per second, once per second, multiple times per minute, once per minute, one or more times per about two minutes, one or more times per about five minutes, one or more times per about ten minutes, one or more times per about 15 minutes, one or more times per about 30 minutes, one or more times per about one hour, one or more times per about two hours, one or more times per about three hours, one or more times per about four hours, one or more times per about six hours, one or more times per about ten hours, one or more times per about twelve hours, one or more times per about 24 hours, one or more times per about 36 hours, one or more times per about 48 hours, one or more times per about one week, one or more times per about two weeks, one or more times per about one month, one or more times per about two months, one or more times per about three months, one or more times per about six months, one or more times per about twelve months, one or more times per about one year, or one or more times per about more than one year.

[0127] The input-and-output circuitry 218 on the flex circuit is communicatively coupled to status LED 230, optical sensors 240, and other components including the conducting pads 250 and 260 on the packaging (e.g., wrapper and liner). The power supply 220 provides power to the flex circuit 210.

[0128] The optical sensors 240, in electrical connection with the input-and-output circuitry 218, may monitor the status change of the smart patch of opening the smart patch 200. The optical sensors 240 may convert the incident light change caused by the status change of the smart patch into an electrical signal, which is detected by the input-and-output circuitry 218. In response, the processor 214 may control the smart patch 200 to transit between working conditions. In some embodiments, the smart patch can transit between working conditions multiple times per second, once per second, multiple times per minute, once per minute, one or more times per about two minutes, one or more times per about five minutes, one or more times per about ten minutes, one or more times per about 15 minutes, one or more times per about 30 minutes, one or more times per about one hour, one or more times per about two hours, one or more times per about three hours, one or more times per about four hours, one or more times per about six hours, one or more times per about ten hours, one or more times per about twelve hours, one or more times per about 24 hours, one or more times per about 36 hours, one or more times per about 48 hours, one or more times per about one week, one or more times per about two weeks, one or more times per about one month, one or more timesWSGR Attorney Docket No. 65297-702.601 per about two months, one or more times per about three months, one or more times per about six months, one or more times per about twelve months, one or more times per about one year, or one or more times per about more than one year.

[0129] In some embodiments, the packaging (e.g., wrapper, liner) of the smart patch 200 may comprise one or more conducting pads 250 and 260. When the packaging is removed by the patient, the electrical connection between the conducting pads 250 / 260 and the input-and- output circuitry 218 may be changed. In response, the processor 214 may control the smart patch 200 to transit between working conditions. In some embodiments, the smart patch can transit between working conditions multiple times per second, once per second, multiple times per minute, once per minute, one or more times per about two minutes, one or more times per about five minutes, one or more times per about ten minutes, one or more times per about 15 minutes, one or more times per about 30 minutes, one or more times per about one hour, one or more times per about two hours, one or more times per about three hours, one or more times per about four hours, one or more times per about six hours, one or more times per about ten hours, one or more times per about twelve hours, one or more times per about 24 hours, one or more times per about 36 hours, one or more times per about 48 hours, one or more times per about one week, one or more times per about two weeks, one or more times per about one month, one or more times per about two months, one or more times per about three months, one or more times per about six months, one or more times per about twelve months, one or more times per about one year, or one or more times per about more than one year.

[0130] In other embodiments, the flex circuit 210 may comprise one or more conducting pads. When the patient applies the smart patch to her skin, the input-and-output circuitry 218 may detect the change in the electrical connection between the conducting pads of the flex circuit 210 and the skin. Accordingly, the processor 214 may control the smart patch 200 to transit between working conditions based on the signal change in the input-and-output circuitry 218.

[0131] FIG. 3 is a non-limiting example of the structure of a smart transdermal drug delivery patch 300 comprising a layer of drug-in-adhesive. The smart patch 300 comprises a backing layer 310, a flex circuit 320, a flex-circuit liner 330, a drug containing layer 340, and a removable liner 350. When the smart patch is applied, the layers 310, 320, 330, 340 and 350 may be stacked over one another in a direction towards the patient skin.

[0132] As an outermost layer of the smart patch 300, the backing layer 310 may be impermeable to external substances and protect drug formulations in the smart patch fromWSGR Attorney Docket No. 65297-702.601 leaking. In some embodiments, the backing layer 310 may be stretchable and occlusive, which brings patient comfort and cosmetic appearance when the smart patch is applied.

[0133] The flex circuit 320 may be positioned between the outermost backing layer 310 and the flex circuit liner 330. In some embodiments, the flex circuit 320 may be a flexible circuit printed on the liner 330. The liner 330 may be an insulating film made of polyimide or polyester materials. The liner 330 may be configured to protect the drug-containing layer 340 from being in contact with the flex circuit 320. The flex circuit 320 may also comprise one or more of conductive layers, adhesive layers, and dielectric layers.

[0134] The drug-containing layer 340 may be a single layer. The drug-containing layer 340 may comprise a single drug-in-adhesive (DIA) layer, where the drug is dissolved or dispersed within adhesive. In some embodiments, the adhesive may comprise silicone, rubber, polyvinyl acetate or polyisobutylene, depending on the skin adhesion properties desired.

[0135] In some embodiments, the drug formulations that are suitable for use in the smart transdermal drug delivery patch may comprise drugs with a size amenable to transdermal delivery. For example, the drugs may have a size range of 100-200 Daltons, 100-300 Daltons, 100-500 Daltons, 100-800 Daltons, or 100-1000 Daltons. In other embodiments, depending on the skin permeabilization mechanisms in the smart patch, the drugs may comprise molecules with a size larger than 1000 Daltons.

[0136] In some embodiments, the drug formulations that are suitable for use in the smart transdermal drug delivery patch may comprise central nervous system (CNS) agents including antipsychotic agents (e.g., olanzapine), anti-smoking agents, anti-anxiety agents, antidepressants, anti-seizure agents, anti-coagulants, or agents for treating alcohol withdrawal syndrome.

[0137] In some embodiments, the antipsychotic agent can comprise olanzapine or a pharmaceutically effective salt thereof. Olanzapine has a structure of

[0138] In some embodiments, the anti-seizure agent can comprise perampanel or a pharmaceutically effective salt thereof. Perampanel has a structure ofWSGR Attorney Docket No. 65297-702.601

[0139] In some embodiments, the drug formulations that are suitable for use in the smart transdermal drug delivery patch may comprise an atrial fibrillation agent. In some embodiments, the atrial fibrillation agent can comprise rivaroxaban or a pharmaceutically effective salt thereof. Rivaroxaban has a structure of

[0140] In some embodiments, the drug formulations that are suitable for use in the smart transdermal drug delivery patch may comprise anti-cancer drugs. The transdermal anti-cancer drugs may substitute oral drugs for cancer treatment with various advantages. For example, the transdermal anti-cancer drugs have an improved bioavailability that avoids the limiting first-pass effect by oral formulations in the gastrointestinal system resulting in a reduced concentration of the drugs upon reaching its site of action or the systemic circulation. The controlled release over hours and days ensures the dosage level remains stable, thereby improving the therapeutic effects of the drug. Non-limiting examples of anti-cancer drugs may comprise drugs treating cancers in adults and in children, including myeloma, breast cancer, renal cancer, etc.

[0141] In some embodiments, the drug formulations that are suitable for use in the smart transdermal drug delivery patch may comprise cardiovascular drugs, central nervous system drugs, psychiatric drugs, antipsychotics, antidepressants, anti-anxiety drugs, anti-seizure drugs, oncologic drugs, chemotherapy drugs, autoimmune drugs, antineoplastic agents, nonsteroidal anti-inflammatory drugs (NSAIDs), antibiotics, analgesics, anti-inflammatory agents, muscle relaxants, anti-epileptics, anti -ulcerative agents, anti-allergic agents, antinausea agents, cardiotonics, anti -arrhythmic agents, vasodilators, anti-hypertensive agents, anti-diabetic agents, anti-hyperlipidemics, anticoagulants, hemolytic agents, antituberculosis agents, hormones, narcotic antagonists, osteoclastic suppressants, osteogenic promoters, angiogenesis suppressors (antianginal), agents for neurodegenerative disease treatment, and various mixtures, salts, prodrugs and co-drugs thereof.WSGR Attorney Docket No. 65297-702.601

[0142] In some embodiments, the drug formulations that are suitable for use in the smart transdermal drug delivery patch may comprise large molecules such as vaccines, oligonucleotides, and peptides. These large molecule drugs may be hydrophilic drugs. For example, a variety of approaches for skin permeabilization may be utilized when applying the smart patch, including novel chemical enhancers, nanocarriers (e.g., solid lipid nanoparticles), ultrasound assisted methods (e.g., sonophoresis), electrically assisted methods (e.g., electroporation and iontophoresis), mechanically assisted methods (e.g., microneedles), thermal approaches (lasers and radio-frequency heating), etc. These approaches may allow a broader class of drugs to be effectively delivered through the skin. These approaches may also allow controlled release of drugs. For example, the smart patch may comprise an iontophoresis mechanism that generates a weak electric current and propels electrically charged drugs across skin into underlying tissues. Alternatively, the smart patch may comprise a sonophoresis mechanism that generates a low-frequency ultrasound wave that may temporarily increase skin permeability and enhances transdermal drug delivery.

[0143] In some embodiments, a drug of any patch, formulation, system, or method provided herein can be a GLP-1 agonist. In some embodiments, provided herein is a transdermal patch (such as a transdermal smart patch provided herein) comprising a GLP-agonist. In some embodiments, the GLP-1 agonist is dulaglutide, exenatide, liraglutide, lixisenatide, semaglutide, and tirzepatide. In some embodiments, the GLP-1 agonist can be delivered at a dose of between about 5pg and about 2mg. In some embodiments, the GLP-1 agonist can be delivered in a continuous dose. In some embodiments, the GLP-1 agonist can be delivered at a dose of about 5pg, 6pg, 7pg, 8pg, 9pg, lOpg, l lpg, 12pg, 13pg, Mpg, 15pg, 16pg, 17pg, 18pg, 19pg, 20pg, 21pg, 22pg, 23pg, 24pg, 25pg, 26pg, 27pg, 28pg, 29pg, 30pg, 31pg,32pg, 33pg, 34pg, 35pg, 36pg, 37pg, 38pg, 39pg, 40pg, 41pg, 42pg, 43pg, 44pg, 45pg,46pg, 47pg, 48pg, 49pg, 50pg, 51pg, 52pg, 53pg, 54pg, 55pg, 56pg, 57pg, 58pg, 59pg,60pg, 61pg, 62pg, 63pg, 64pg, 65pg, 66pg, 67pg, 68pg, 69pg, 70pg, 71pg, 72pg, 73pg,74pg, 75pg, 76pg, 77pg, 78pg, 79pg, 80pg, 81pg, 82pg, 83pg, 84pg, 85pg, 86pg, 87pg,88pg, 89pg, 90pg, 91pg, 92pg, 93pg, 94pg, 95pg, 96pg, 97pg, 98pg, 99pg, lOOpg, or more than lOOpg. In some embodiments, the GLP-1 agonist can be delivered at a dose of about O.lmg, 01.2mg, 0.3mg, 04mg, 0.5mg, 0.6mg, 0.7mg, 0.8mg, 0.9mg, Img, . Img, 1.2mg, 1.3mg, 1.4mg, 1.5mg, 1.6mg, 1.7mg, 1.8mg, 1.9mg, 2mg, or more than 2mg.

[0144] In some embodiments, the drug-containing layer 340 may comprise a single drug. Alternatively, the drug-containing layer 340 may comprise two or more drugs. In some embodiments, the drug-containing layer 340 may comprise one or more placebos. DuringWSGR Attorney Docket No. 65297-702.601 clinical trials, smart patches comprising placebos may be applied to a control group of participants, in comparison with an experimental group of participants to whom drugcontaining smart patches are applied.

[0145] The drug-containing layer 340 may comprise excipients that may be characterized by functions, for example, solubilizers, penetration / permeation enhancers, retarders, and preservative / stabilizers. Non-limiting examples of excipients may comprise anti-adherent agents, anti-caking agents (e.g., additives such as silica or talc); antioxidants that prevent the oxidation and deterioration of components within the drug-containing layer. Non-limiting examples of antioxidants may comprise ascorbic acid, butylated hydroxyanisole (BHA), and BHT. Other examples of excipients may comprise buffering agents (e.g., sodium bicarbonate and calcium biphosphate) designed to maintain the pH value of the drug formulation, diluents / fillers (e.g., calcium carbonate and lactose), emulsifying agents that enhance the emulsion stability and avoids phase separation (e.g., simethicone emulsion, sodium lauryl sulfate, polysorbate 60), glidants added to drug formation in powder or granule forms to enhance the flowability (e.g., silica and silica derivatives), preservatives that prolongs the shelf life of the smart patch by protecting them from micro-organism deterioration (e.g., benzoic acid and butylparaben).

[0146] In some embodiments, the excipients may comprise one or more chemical enhancers. Chemical enhancers may temporarily dissolve stratum corneum and facilitate the transport of drug formulations to controlled depth in tissues. Chemical enhancers may comprise one or more of anionic surfactants, cationic surfactants, zwitterionic surfactants, nonionic surfactants, fatty acids, fatty esters, fatty amines, Azone-like compounds, sodium salts of fatty acids, sulphoxides and similar chemicals, pyrrolidones, essential oil, terpenes and terpenoids.

[0147] In some embodiments, the transdermal formulation may comprise an active ingredient in any suitable amount, such as 0.1 mg to 1g.

[0148] As illustrated in FIG. 3, the smart patch 300 further comprises a liner 350. The liner 350 may protect the drug-in-adhesive and need to be removed prior to smart patch application.

[0149] FIG. 4 is a non-limiting example of the structure of a smart transdermal drug delivery patch 400 comprising a plurality of layers of drug-in-adhesive. The smart patch 400 comprises a backing layer 410, a flex circuit 420, a flex-circuit liner 430, a drug containing layer 440, and a removable liner 450. When the smart patch is applied, the layers 410, 420, 430, 440 and 450 may be overlapped with one another in a direction towards patient skin.WSGR Attorney Docket No. 65297-702.601

[0150] Different from the drug containing layer 340 comprising a single layer of drug-inadhesive, the drug containing layer 440 comprises multiple layers of drug-in-adhesive. As illustrated, a first layer of drug-in-adhesive 442 is stacked over a second layer of drug-inadhesive 446, with a membrane 444 positioned therebetween. Multiple layers of drug-inadhesive may carry a larger amount of drug formulations, such that the use life of the smart patch may be substantially extended. The membrane 444 between the drug-in-adhesive layers 442 and 446 may control the diffusion of drugs for extended release. The membrane 444 may be made of natural or synthetic polymer or synthetic elastomers. The thickness of the membrane 444 may range from about 2 mm to about 7 mm.

[0151] FIG. 5 is a non-limiting example of the structure of a smart transdermal drug delivery patch 500 comprising a drug reservoir. The smart patch 500 comprises a backing layer 510, a flex circuit 520, a flex-circuit liner 530, a drug containing layer 540, and a removable liner 550. When the smart patch is applied, the layers 510, 520, 530, 540 and 550 may be overlapped with one another in a direction towards the patient skin.

[0152] The drug-containing layer 540 comprises a drug reservoir 542, a membrane 544, and an adhesive layer 546 overlapped with one another. Unlike drug-in-adhesive layer(s) that contain a mixture of drug and adhesive, here, the drug formulation is stored in the drug reservoir 542 and separate from the adhesive layer 546. The membrane 544 between the drug reservoir 542 and the adhesive layer 546 may control the diffusion of drugs for extended release. When the smart patch 500 is applied to the skin, the drug may slowly diffuse from the reservoir 542 through the rate-controlling membrane 544 and the adhesive 546 to the skin.

[0153] FIG. 6 is a non-limiting example of the structure of a smart transdermal drug delivery patch 600 comprising a drug reservoir and an adhesive ring therearound. The smart patch 600 comprises a backing layer 610, a flex circuit 620, a flex-circuit liner 630, a drug containing layer 640 and a removable liner 650. When the smart patch is applied, the layers 610, 620, 630, 640 and 650 may be overlapped with one another in a direction towards patient skin.

[0154] The drug-containing layer 640 comprises a drug reservoir 642 surrounded by an adhesive ring 644. In some embodiments, the drug reservoir 642 may comprise a drugcontaining polymer matrix in direct contact with the skin. The drug reservoir 642 may include one or more cavities formed by a polymer structure and may include one or more ion exchange membranes (e.g., electroactive polymer membranes), semi-permeable membranes, porous membranes and / or gels that are capable of at least temporarily retaining an element or compound.WSGR Attorney Docket No. 65297-702.601

[0155] When the smart transdermal drug delivery patch comprises a drug reservoir as illustrated in FIGS. 5 and 6, the drugs that are suitable for use may have an expected dosage range to fit the size of the reservoir. For example, for a smart transdermal drug delivery patch with 24-170 hours of use life, a daily dosage range may be less than 50 mg, less than 45 mg, less than 40 mg, less than 35 mg, less than 30 mg, less than 25 mg, or less than 20 mg.

[0156] FIG. 7 is a non-limiting example of the structure of a smart transdermal drug delivery patch 700 comprising a drug-containing microneedle array. The smart patch 700 comprises a backing layer 710, a flex circuit 720, a flex-circuit liner 730, a drug containing layer 740, and a removable liner 750. When the smart patch 700 is applied, the layers 710, 720, 730, 740 and 750 may be overlapped with one another in a direction towards the patient skin.

[0157] The drug-containing layer 740 comprises a microneedle array 742, in direct contact with the skin, with an adhesive layer 744. In some embodiments, the adhesive layer 744 may be surrounding the microneedles to adhere to the skin. The microneedles may pierce holes into the skin to increase transport by diffusion or iontophoresis or as drug carriers that release drug into the skin in a controllable manner. The microneedle array may substantially increase skin permeability and efficiency in the transdermal delivery, especially for hydrophilic molecules and macromolecules (e.g., peptides, DNA, RNA). In some embodiments, the microneedles may be made of polymer and dissolvable after pierced into the skin.

[0158] In some embodiments, the delivery of the drug from the TET platform is passive delivery. In some embodiments, the passive delivery of the drug from the TET platform begins upon attachment of the TET smart patch to the patient’s skin. In some embodiments, the patch is not activated to release the drug by any signaling. In some embodiments’ the drug is automatically delivered with no activation required.

[0159] FIG. 8 illustrates detection of a status change of the smart patch of removing a packaging from a smart transdermal drug delivery patch 800 using one or more sensors. The smart patch 800 comprises a backing layer 810, a flex circuit 820, a flex circuit liner 830, a drug containing layer 840 and a removable liner 850. When the smart patch is applied, the layers 810, 820, 830, 840 and 850 may be overlapped with one another in a direction towards patient skin. The drug-containing layer 840 may be any of the drug-containing layers 340, 440, 540, 640, and 740 as illustrated in FIGs. 3-7. The smart patch 800 is packed by a removable wrapper 860.

[0160] As illustrated, the flex circuit 820 comprises one or more conducting pads 822 and sensors 824 (e.g., sensing circuit). The inner surface of the wrapper 860 is in contact with theWSGR Attorney Docket No. 65297-702.601 backing layer 810 and comprises one or more conducting pads 862 and conducting traces 864 that are in electrical connection. One or more pass-through holes 812 are present on the backing layer 810. The positions of the pass-through holes 812 are aligned with the conducting pads 862 on the wrapper 860 and the conducting pads 822 on the flex circuit 820. When the wrapper 860 wraps around the smart patch 800, the conducting pads 862 and 822 are electrically connected via the conducting traces 864, thereby forming a sensing signal path. The flex circuit 820 may apply a voltage to the conducting pads 822, which induces a current measured by the sensors 824. When the patient removes the wrapper 860, the electrical connection is interrupted. The sensors 824 on the flex circuit 820 detects the current decrease caused by the disconnection. In some embodiments, the flex circuit can apply a voltage to the conducting pads constantly, or multiple times per second, once per second, multiple times per minute, once per minute, one or more times per about two minutes, one or more times per about five minutes, one or more times per about ten minutes, one or more times per about 15 minutes, one or more times per about 30 minutes, one or more times per about one hour, one or more times per about two hours, one or more times per about three hours, one or more times per about four hours, one or more times per about six hours, one or more times per about ten hours, one or more times per about twelve hours, one or more times per about 24 hours, one or more times per about 36 hours, one or more times per about 48 hours, one or more times per about one week, one or more times per about two weeks, one or more times per about one month, one or more times per about two months, one or more times per about three months, one or more times per about six months, one or more times per about twelve months, one or more times per about one year, or one or more times per about more than one year.

[0161] In response to the status change of the smart patch of removing the wrapper, the processor (e.g., processors 120 and 214 in FIGs. 1 and 2) may control the smart patch to transit between working conditions. In some embodiments, the processor may control the smart patch to transit from the hibernation mode, which is a default mode from manufacture, to a non-hibernation mode (e.g., sleep mode and work mode).

[0162] FIG. 9 illustrates detection of a status change of the smart patch of opening a smart transdermal drug delivery patch 900 using one or more optical sensors. The smart patch 900 comprises a backing layer 910, a flex circuit 920, a flex-circuit liner 930, a drug containing layer 940, and a removable liner 950. When the smart patch is applied, the layers 910, 920, 930, 940 and 950 may be overlapped with one another in a direction towards patient skin. Each of the backing layers 910, flex circuit liner 930, and drug-containing layer 940WSGR Attorney Docket No. 65297-702.601 comprises one or more transparent windows (or pass-through holes) 912, 932, and 942, respectively. The flex circuit 920 comprises one or more optical sensors 922 aligned with the transparent windows 912, 932, and 942, such that ambient light may pass through from the transparent windows and be detected by the optical sensors 922.

[0163] The patient may open the smart patch prior to applying it to the skin by removing the packaging (e.g., wrapper) from the smart patch. The optical sensor 922 may detect ambient light passed through from the transparent window 912 upon the removal of the wrapper. In response to this status change of the smart patch, the processor may control the smart patch to remain the current working condition of the smart patch, for example, at the sleep mode or work mode. Alternatively, if the previous status change of the smart patch of removing the wrapper failed to “wake up” the smart patch, upon the opening of the smart patch, the processor may control the smart patch to transit from the hibernation mode to a nonhibernation mode.

[0164] In some embodiments, one or more sensors of a TET smart patch may activate in response to a package surrounding the TET smart patch or attached to the TET smart patch being manipulated or opened. In some embodiments, one or more sensors of the TET smart patch can be activated when a seal of a packaging surrounding the TET smart patch or attached to the TET smart patch is broken. In some embodiments, the TET smart patch can complete an electric circuit with a low-energy electrical current when in the packaging. In some embodiments, manipulating one or more parts of the packaging, like breaking a seal, peeling back a portion of the package, ripping or poking one or more parts of the package, or disconnecting a part of the package, for example, can activate the one or more sensors. The sensors can be, for example, light sensors, electricity sensors, pressure sensors, infrared sensors, sound sensors, ultrasound sensors, gas sensors, capacitive sensors, humidity sensors, touch sensors, temperature sensors, magnetic field sensors, resistive sensors, or any combination thereof.

[0165] The patient may further remove the liner 950 that covers the drug-containing layer 940. The optical sensor 922 may detect ambient light passed through the transparent windows 942 and 932 caused by the removal of the liner 950. The processor may control the smart patch to remain the current working condition, for example, at the sleep mode or work mode. Alternatively, if the previous status change of the smart patches failed to trigger the transition of working conditions, the processor may control the smart patch to transit to work mode.

[0166] Following the removal of the liner 950, the patient may apply the smart patch to her skin. Ambient light passing through the transparent window 942 may be blocked because theWSGR Attorney Docket No. 65297-702.601 drug-containing layer 940 is in direct contact with the skin. The optical sensor 922 may detect the change in ambient light. The processor in the smart patch may control the working condition of the smart patch 900. For example, if the smart patch was at the sleep mode, when being applied to patient skin, the processor may control the smart patch to transit to the work mode.

[0167] In some embodiments, the flex circuit 920 may further comprise one or more optical sensors used as a real time calibrator and differential comparator to ensure reliable detection with variable lighting conditions. The optical sensors may be positioned on the flex circuit 920 and away from the transparent windows 912, 932, and 942, such that the calibration and differential comparison are not impacted by ambient light change caused by status change of the smart patch to the smart patch.

[0168] FIG. 10 illustrates detection of a status change of the smart patch of removing a liner from a smart transdermal drug delivery patch 1000 using one or more sensors. The smart patch 1000 comprises a backing layer 1010, a flex circuit 1020, a flex-circuit liner 1030, a drug containing layer 1040, and a removable liner 1050. When the smart patch is applied, the layers 1010, 1020, 1030, 1040 and 1050 may be overlapped with one another in a direction towards patient skin. As illustrated, the flex circuit 1020 comprises one or more of conducting pads 1022 and sensors 1024 (e.g., sensing circuit). The inner surface of the liner 1050 is in direct contact with the drug-containing layer 1040 and comprises one or more of conducting pads 1052 and conducting traces 1054 that are in electrical connection. Pass- through holes 1032 and 1042 are present on the flex circuit liner 1030 and drug-containing layer 1040, respectively. The positions of the pass-through holes 1032 and 1042 are aligned with the conducting pads 1022 on the flex circuit 1020 and conducting pads 1052 on the liner 1050. When the liner 1050 is in direct contact with the drug-containing layer 1040, the conducting pads 1022 and 1052 are electrically connected via the conducting traces 1054, thereby forming a sensing signal path. The flex circuit 1020 may apply a voltage to the conducting pads 1022, which induces a current measured by the sensors 1024. When the patient removes the liner 1050, the electric connection is interrupted. The sensors 1024 on the flex circuit 1020 may detect the current decrease caused by the disconnection. The processor in the smart patch may control the smart patch to maintain the current working condition of the smart patch, for example, at the sleep mode or work mode. In some embodiments, the processor may control the smart patch to transit between working conditions.

[0169] FIG. 11 illustrates detection of a status change of the smart patch of applying a smart transdermal drug delivery patch 1100 to patient skin using one or more sensors. The smartWSGR Attorney Docket No. 65297-702.601 patch 1100 comprises a backing layer 1110, a flex circuit 1120, a flex-circuit liner 1130, and a drug containing layer 1140. When the smart patch is applied, the layers 1110, 1120, 1130, and 1140 may be overlapped with one another in a direction towards patient skin. In this scenario, both the wrapper (e.g., wrapper 860 in FIG. 8) and the liner (e.g., liner 850, 950, 1050 in FIGs. 8-10, respectively) are removed. The smart patch is ready to be applied to patient skin.

[0170] As illustrated, the flex circuit 1120 comprises conducting pads 1122 and sensors 1124 (e.g., sensing circuit). Pass-through holes 1132 and 1142 are present on the flex circuit liner 1130 and drug-containing layer 1140, respectively. The positions of the pass-through holes 1132 and 1142 are aligned with the conducting pads 1122 on the flex circuit 1120. When the smart patch is applied, the conducting pads 1122 are in direct contact with the skin (see skin contact point and conducting path in FIG. 11) through the pass-through holes 1132 and 1142. The conducting pads 1122 and the skin contact points form an electrical connection. When the flex circuit 1120 applies a voltage to the conducting pads 1122, a current may be generated and detected by the sensors 1124. In response, the processor may control the smart patch to transit between working conditions, for example, from sleep mode to work mode. Alternatively, if previous status change of the smart patches already triggered the smart patch to transit to work mode, the processor may maintain the working condition.

[0171] After the smart patch is applied, the processor may stay in sleep mode, which is a low-powered and default mode. Upon receiving a sensing event corresponding to a status change of the smart patch detected by the sensors, the processor may control the smart patch to transit from sleep mode to work mode. Alternatively or additionally, upon receiving a communication signal (e.g., an alert or message from other devices in the network) from the communication interface, the processor may control the smart patch to transit from sleep mode to work mode. In some embodiments, the smart patch in sleep mode can minimize power consumption and extend the use life of the smart patch. In some embodiments, the smart patch can receive a communication signal or sensing event multiple times per second, once per second, multiple times per minute, once per minute, one or more times per about two minutes, one or more times per about five minutes, one or more times per about ten minutes, one or more times per about 15 minutes, one or more times per about 30 minutes, one or more times per about one hour, one or more times per about two hours, one or more times per about three hours, one or more times per about four hours, one or more times per about six hours, one or more times per about ten hours, one or more times per about twelve hours, one or more times per about 24 hours, one or more times per about 36 hours, one orWSGR Attorney Docket No. 65297-702.601 more times per about 48 hours, one or more times per about one week, one or more times per about two weeks, one or more times per about one month, one or more times per about two months, one or more times per about three months, one or more times per about six months, one or more times per about twelve months, one or more times per about one year, or one or more times per about more than one year.

[0172] In some embodiments, one or more communication signals can control the smart patch mode to improve battery performance. In some embodiments, one or more communication signals from the communication interface of the TET patch can cause the TET patch to exit sleep mode to improve performance at the expense of battery life. In some embodiments, work mode can increase battery power usage and improve performance of the TET patch. In some embodiments, sleep mode can decrease battery power usage and improve battery life of the printable battery of the TET system.

[0173] The present disclosure provides various mechanisms for improving the reliability of detecting and identifying status change of the smart patch to the smart patch, and based on the types of status change of the smart patch, controlling the smart patch to transit between working conditions.

[0174] In some embodiments, multiple pairs of conducting pads may be present on the flex circuit and packaging (e.g., wrapper and liner), and generate redundant signals that can be detected by the sensors. Moreover, a plurality of pairs of conducting pads on the flex circuit may monitor the electrodermal response of the patient wearing the smart patch. The smart patch may comprise algorithms stored in memory (e.g., System-on-a-Chip (SoC) embedded algorithms) for analyzing these electrodermal responses for clinical data collection and monitoring.

[0175] In some embodiments, the processor may determine whether the signals generated from different sensors are consistent and point to the same status change of the smart patch. When signal changes detected by different sensors are inconsistent, the process may generate an alert signal indicating inconsistent status change of the smart patch being identified or malfunction of the smart patch. For example, when the patient removes the wrapper from the smart patch, the electrical connection between the conducting pads 822 / 862 and conducting trace 864 no longer exists (see, e.g., FIG. 8). The sensors 824 may detect the current decrease, and the processor may identify the status change of the smart patch of removing the wrapper and control the smart patch to transit among working conditions. As the smart patch is exposed or opened, the optical sensor 922 may detect ambient light increase from the pass- through holes 912 in the backing layer (see, e.g., FIG. 9). When the light change is consistentWSGR Attorney Docket No. 65297-702.601 with the electrical signal change, they may point to the same status change of the smart patch of removing the wrapper. The sensors can be, for example, light sensors, electricity sensors, piezoelectric sensors, pressure sensors, infrared sensors, sound sensors, ultrasound sensors, gas sensors, capacitive sensors, humidity sensors, touch sensors, temperature sensors, magnetic field sensors, or any combination thereof.

[0176] When the patient removes the liner and exposes the drug-containing layer, the electrical connection between the conducting pads 1022 / 1052 and conducting trace 1054 on the liner no longer exists (see, e.g., FIG. 10). The sensors 1024 may detect the current decrease, and the processor may identify the status change of the smart patch of removing the liner. The optical sensor 922 may detect ambient light increase from the pass-through holes 942 and 932 in the drug-containing layer and flex circuit liner (see, e.g., FIG. 9). The light change is consistent with the electrical signal change, pointing to the same status change of the smart patch of removing the liner.

[0177] When the patient applies the smart patch to her skin, an electrical connection is established between the skin contact points and the conducting pads 1122 on the flex circuit 1120 (see FIG. 11). The sensors 1124 may detect the current increase, and the processor may identify the status change of the smart patch of applying the smart patch. The optical sensor 922 may detect ambient light decrease because ambient light from the pass-through hole 942 on the drug-containing layer 940 is blocked by the skin (see, e.g., FIG. 9). The light change is consistent with the electrical signal change, pointing to the same status change of the smart patch of applying the smart patch.

[0178] When the patient removes the smart patch from her skin, the electrical connection between the skin contact points and the conducting pads on the flex circuit no longer exists. The sensors may detect the current decrease, and the processor may identify the status change of the smart patch of removing the smart patch and control the smart patch to transit between working conditions. The optical sensor may detect light increase as ambient light passes from the pass-through holes on the drug-containing layer and flex circuit liner. The light change is consistent with the electrical signal change, pointing to the same status change of the smart patch of removing the smart patch.

[0179] In some embodiments, the removal of the smart patch may be unintentional, for example, the smart patch may accidentally fall off the skin. When the patient re-applies the smart patch to her skin within a pre-determined time threshold, the electrical connection is reestablished between the skin contact points and the conducting pads on the flex circuit, and detected by the sensors. In consistency with the status change of the smart patch, the lightWSGR Attorney Docket No. 65297-702.601 sensor may detect light change when the smart patch is applied. The processor may control the smart patch to transit from sleep mode to work mode again. In some embodiments, one or more communication signals can control the smart patch mode to improve battery performance. In some embodiments, one or more communication signals from the communication interface of the TET patch can cause the TET patch to exit sleep mode to improve performance at the expense of battery life. In some embodiments, work mode can increase battery power usage and improve performance of the TET patch. In some embodiments, sleep mode can decrease battery power usage and improve battery life of the printable battery of the TET system. Nevertheless, when the duration of the removal exceeds the pre-determined time threshold, it may indicate the patient has either completed the dose or terminated the use of the smart patch. The processor may control the smart patch to transit to the hibernation mode.

[0180] The processor may further differentiate status change of the smart patch and ensure each action is accurately and reliably detected. The flex circuit may apply different voltages to the conducting pads and conducting traces on the circuit, thereby generating different magnitudes of current detected by the sensors. For example, the flex circuit may generate a larger current corresponding to the status change of the smart patch of removing the liner from the smart patch than the action of applying the smart patch to the skin. By differentiating status change of the smart patch, the processor may accurately control the working conditions of the smart patch in response to the actions.

[0181] FIG. 12 illustrates a process 1200 of treating a patient in need thereof using a transdermal drug delivery smart patch. The process comprises determining a status change of the smart patch to a smart patch using one or more sensors associated with the smart patch (step 1210), and automatically transiting between a plurality of working conditions of the smart patch based on the determined status change of the smart patch (see step 1220). The plurality of working conditions may comprise a hibernation mode, a sleep mode, and a work mode.

[0182] FIG. 13 illustrates correlations between triggering events and corresponding working conditions of a transdermal drug delivery smart patch. Upon completion of manufacture (see 1310), the smart patch is at hibernation mode (see 1320). The power of the smart patch is off. The smart patch does not send out or receive communication signals. Subsequently, a patient receives the smart patch and removes the packaging including the wrapper and liner from the smart patch (see 1330). The sensors within the smart patch detect these status change of the smart patches. Accordingly, the processor transits the smart patch from the hibernation modeWSGR Attorney Docket No. 65297-702.601 to a non-hibernation mode, for example, sleep mode or work mode (see 1340). The patient subsequently applies the smart patch to her skin (see 1350), which is detected by the sensors in the smart patch. During the normal use of the smart patch, the smart patch may remain in sleep mode for energy saving purpose (see 1380). When the sensors detect another status change of the smart patch on the smart patch or receives a communication signal via the communication interface, the processor may control the smart patch to transit from sleep mode to work mode (see 1360). Alternatively, the processor may control the smart patch to switch between the sleep mode and the work mode periodically. When the smart patch is switched to the work mode, the processor may transmit smart patch usage data, a current working condition of the smart patch, transitions of working conditions, a state of sensors, a sequence of state changes, date and time stamp of each state change, a unique smart patch identifier via the communication interface. When the patient removes the smart patch (see 1370), depending on the duration of the removal, the smart patch may stay at the sleep mode or transit to the hibernation mode (see 1390). In some embodiments, one or more communication signals can control the smart patch mode to improve battery performance. In some embodiments, one or more communication signals from the communication interface of the TET patch can cause the TET patch to exit sleep mode to improve performance at the expense of battery life. In some embodiments, work mode can increase battery power usage and improve performance of the TET patch. In some embodiments, sleep mode or hibernation mode can decrease battery power usage and improve battery life of the printable battery of the TET system.

[0183] The present disclosure further provides a method of enhancing drug compliance of a patient in need thereof using a transdermal drug delivery smart patch. In some embodiments, enhancing drug compliance can comprise increasing compliance with a medication protocol. In some embodiments, enhancing drug compliance can comprise increasing a probability that a patient will comply with a treatment. In some embodiments, enhancing drug compliance can comprise increasing the percentage of a population that comply with a treatment protocol. The method may comprise receiving, from the smart patch via a wireless network, information associated with a plurality of working conditions of the smart patch. The method may further comprise generating smart patch usage data based on the plurality of working conditions of the smart patch, wherein the smart patch usage data comprises at least one of a status change of the smart patch to the smart patch, a dose of a drug administered to the patient, a timing of the dose, or a frequency of doses. The status change of the smart patchWSGR Attorney Docket No. 65297-702.601 may comprise one or more of removing a packaging from the smart patch, applying the smart patch to skin of the patient, and removing the smart patch from the skin of the patient.

[0184] The present disclosure further provides a method of monitoring drug compliance of a patient in need thereof using a transdermal drug delivery smart patch. In some embodiments, monitoring drug compliance can comprise monitoring compliance of the patient with a medication protocol at a single time point. In some embodiments, monitoring drug compliance can comprise monitoring compliance of the patient with a medication protocol at multiple time points. In some embodiments, monitoring drug compliance can comprise monitoring compliance of more than one patient with a medication protocol at a single time point or at multiple time points. In some embodiments, monitoring drug compliance can comprise aggregating drug compliance data for a population over one time point or multiple time points. The method may comprise receiving, from the smart patch via a wireless network, information associated with a plurality of working conditions of the smart patch. The method may further comprise generating smart patch usage data based on the plurality of working conditions of the smart patch, wherein the smart patch usage data comprises at least one of a status change of the smart patch to the smart patch, a dose of a drug administered to the patient, a timing of the dose, or a frequency of doses. The status change of the smart patch may comprise one or more of removing a packaging from the smart patch, applying the smart patch to skin of the patient, and removing the smart patch from the skin of the patient.

[0185] The present disclosure further provides a transdermal drug delivery system comprising a smart transdermal drug delivery patch and a backend application system comprising one or more computer processors that are individually or collectively programmed to perform operations. The smart patch comprises a drug-containing layer, a communication interface, one or more sensors configured to detect a status change of the smart patch to the smart patch, and a processor communicatively coupled to the one or more sensors and the communication interface. The status change of the smart patch comprises one or more of removing a packaging from the smart patch, applying the smart patch to skin of the patient, and removing the smart patch from the skin. The processors in the backend application system are programmed to perform operations comprising receiving, from the smart patch, information associated with the plurality of working conditions of the smart patch via the wireless network, generating smart patch usage data based on the plurality of working conditions of the smart patch, wherein the smart patch usage data comprises one or more of the status change of the smart patches, a dose of a drug administered to the patient, a timing of the dose, or a frequency of doses, and determining drug compliance of the patientWSGR Attorney Docket No. 65297-702.601 based on the smart patch usage data and the medical record of the patient saved on the wireless network.

[0186] FIG. 14 illustrates a smart transdermal drug delivery patch connected to a wireless network. A networked system 1400 comprises one or more smart patches 1410 as described herein, and a plurality of user devices that are connected to a network 1430. The user devices comprise patient devices 1420 and 1440, devices 1450 and 1460 associated with caregivers and health care providers, and devices 1470 associated with business operators (e.g., insurance and pharmacy) associated with the patient healthcare.

[0187] In some embodiments, the smart patch 1410 may be connected in a mesh network. In other embodiments, the smart patch 1410 may be connected in an Intern et-of-Things (loT) network. As illustrated, the smart patch 1410 is connected with patient home devices 1420 and mobile devices 1440 via the network. The home devices may comprise personal assistance and home assistance devices including speakers, displays, phones, tablets, phablets, watches, glasses, and other personal and home electronics. The smart patch 1410 may transmit to and receive signals on the loT network via the communication interface. The smart patch 1410 may transmit smart patch usage data to other devices (e.g., mobile devices 1440) in the network, including but not limited to status change of the smart patch, a dose of the drug, an overdose of the drug, a missed dose, an aborted dose, a timing of the dose, a frequency of doses, a current working condition of the smart patch, transitions of working conditions of the smart patch, a state of the sensors in the smart patch, a sequence of state changes of the sensors, a timing of each state change, a unique smart patch identifier.

[0188] The smart patch 1410 may be connected to the network using a communication protocol selected from the group consisting of short-range wireless signals, wireless network signals, near-field communication (NFC) signals, broadband, narrow band-internet of Things (NB-IoT), radio signals, WLAN, cellular signals, and future revisions of the aforementioned protocol standards. In some embodiments, the communication interface of the smart patch may comprise a short-range wireless signals low energy radio (LER) (e.g., 216 as illustrated in FIG. 2), which communicates with other devices in the network via LER. In some embodiments, the communication may take place in the signal range of about 2.4GHz to about 2.5GHz.

[0189] In some embodiments, the smart patch 1410 may be compatible with a long-range encrypted network, a low-bandwidth and long-range wireless communication protocol that uses LER for short distance communication and LoRa for longer distance communication. The smart patch 1410 may transmit signals to in-range compatible devices, including mobileWSGR Attorney Docket No. 65297-702.601 devices, trackers smart speakers, and home assistance devices. As the patient wearing the smart patch is on the move, her mobile device may transmit geolocation data of the patient / smart patch to the network periodically.

[0190] The present disclosure further provides a backend application system comprising one or more computer processors that are individually or collectively programmed to perform operations for enhancing drug compliance of patients who use transdermal drug delivery smart patches. In some embodiments, enhancing drug compliance can comprise increasing compliance with a medication protocol. In some embodiments, enhancing drug compliance can comprise increasing a probability that a patient will comply with a treatment. In some embodiments, enhancing drug compliance can comprise increasing the percentage of a population that comply with a treatment protocol.

[0191] The present disclosure further provides a backend application system comprising one or more computer processors that are individually or collectively programmed to perform operations for monitoring drug compliance of patients who use transdermal drug delivery smart patches. In some embodiments, monitoring drug compliance can comprise monitoring compliance of the patient with a medication protocol at a single time point. In some embodiments, monitoring drug compliance can comprise monitoring compliance of the patient with a medication protocol at multiple time points. In some embodiments, monitoring drug compliance can comprise monitoring compliance of more than one patient with a medication protocol at a single time point or at multiple time points. In some embodiments, monitoring drug compliance can comprise aggregating drug compliance data for a population over one time point or multiple time points.

[0192] The backend application system and the smart patch may be connected to a wireless network, where the backend application may receive and process smart patch usage data from the smart patch, and determine whether the patient adheres to her drug administration. The backend application system may comprise a cloud computing system. Alternatively, the backend application system may comprise a computing system in other user devices in the network. Patients, health care providers / caregivers, and business operators may access smart patch usage data, and drug compliance information from web application, mobile application, or the like.

[0193] The backend application system may receive patient data from the network. The patient data may comprise clinical data, including but not limited to drug prescription, an expected dosage, an expected timing of administering the drug. The clinical data may also comprise an electronic health record (EHR) and demographic information of the patientWSGR Attorney Docket No. 65297-702.601 stored in the network. The backend application system may receive smart patch usage data from the network. In some embodiments, the smart patch usage data may comprise smart patch actions to the smart patch, a current working condition of the smart patch, transitions of working conditions of the smart patch, a state of the sensors in the smart patch, a sequence of state changes and a timing of each state change. Based on the smart patch usage data, the backend application system may determine a timing of a dose (i.e., when the patient applies the smart patch), the duration of the smart patch application, a dose of the drug based on the duration of the smart patch use, any interruption during the smart patch use, a frequency of doses, etc.

[0194] In some embodiments, by comparing the patient’s smart patch usage data and clinical data, the backend application system may determine the drug compliance of the patient. For example, when the drug prescription and expected dosage of a drug are inconsistent with the smart patch use, the backend application system may determine it is likely that the patient misses a dose, shortens or terminates a dose, overdoses, or otherwise fails to follow a scheduled course of treatment. The backend application system may generate and transmit an alert signal to the patient device (e.g., smart speaker 1420 and mobile device 1440), requesting drug compliance from the patient. In addition, the backend application system may transmit the alert signal to other user devices in the network including caregiver devices 1450, health care provider devices 1460 and business operator devices 1470 for monitoring the patient’s drug compliance and medical record keeping.

[0195] In some embodiments, the backend application system may monitor the health condition of the patient during the smart patch use and intervene when necessary. When the patient wears an in-network device that measures physiological parameters of the patient, or a device that monitors geolocation, physical activity, and motion of the patient, these devices may transmit data associated with the patient to the network. Based on the received smart patch usage data and patient data, the backend application system may determine the change in the patient’s health condition. For example, the patient may have an adverse drug reaction to the drug, which is reflected as a rapid change in her physiological parameters. The patient may suffer a sudden fall during the smart patch use or perform physical activities that are incompatible with the current drug administration, both of which can be monitored by motion sensors. The backend application system may generate and transmit an alert or intervention message to the patient device (e.g., smart speaker 1420 and mobile device 1440), providing suggestions or assistance to the patient. In addition, the backend application system mayWSGR Attorney Docket No. 65297-702.601 transmit the alert signal to other user devices in the network, such health care providers may provide urgent care in a timely manner.

[0196] In some embodiments, when user devices are connected to the network, the backend application system may provide authorized users access to the patient’s record of smart patch use, along with medical record and other associated information. For example, the backend application system may provide smart patch usage data, drug compliance information, notifications (e.g., alerts or intervention messages) to the patient devices, such that the patient can easily monitor her drug administration and compliance on her mobile or web application, with an improved user experience. The backend application system may send smart patch usage data and drug compliance information to caregivers and health providers. Because smart patch usage data accurately reflects drug compliance of the patient and is generated automatically, caregivers and health providers can monitor the drug compliance and health conditions of the patient in real time. The indirect monitoring relying on questionnaires and patient self-reports can be avoided. Furthermore, as the backend application system receives and processes both smart patch usage data from the smart patch and clinical responses (e.g., real time physiological parameters) from other devices in the network, the backend application system may provide a direct assessment of drug compliance. Patients do not need to go to hospitals and clinics to measure drug / metabolite levels for drug adherence assessment.

[0197] In some embodiments, notifications can comprise push notifications, text messages, calls, emails, banners, in-app alerts, voice alerts, audio tones, spoken alerts, or other sounds, visual signals, light signals, vibration signals such as vibration of one or more technological devices, electrical current signals across the skin or a device, or physical manipulation of one or more objects.

[0198] In some embodiments, notifications can be provided for misuse of the smart patch, misuse of one or more medications, one or more missed medication schedules, application of too many smart patches, application of too few smart patches, application of one or more incorrectly medicated smart patches, application of one or more expired medication smart patches, application of one or more defective smart patches, application of one or more smart patches to an incorrect area of the body, application of one or more smart patches for a time period that is too short, application or one or more smart patches for a time period that is too long, accidental detachment of one or more smart patches from the skin, intentional detachment of one or more smart patches from the skin, incomplete application of one or more smart patches, damage to one or more smart patches, application of one or more smartWSGR Attorney Docket No. 65297-702.601 patches with incorrect dosage of medication, application of one or more smart patches with incomplete or incorrect accompanying validation or security information, or another type of notification.

[0199] In some embodiments, notifications can be provided to authorized users. Authorized users can include relatives of the patient, friends of the patient, or care providers of the patient. Care providers of the patient can include medical personnel such as the patient’s physician team, at-home care team, nursing team, nursing home staff, or other healthcare worker(s).

[0200] In some embodiments, the networked system 1400 may provide data storage functions. The network system 1400 may comprise one or more databases that store information associated with patients, including smart patch usage data, electronic health record (e.g., diagnoses, medicines, tests, allergies, immunizations, and treatment plans), physiological parameters and activities obtained from wearable devices, social history (e.g., alcohol and tobacco use), demographic information, mental health conditions, insurance information, and the like. The backend application system may analyze smart patch usage data in combination with other patient associated data stored in the network and determine the drug compliance of the patient in an efficient and effective manner.Computer System

[0201] As described in some of the aforementioned embodiments, the smart patch and backend application system may comprise a computer system, including one or more processors, memory, and storage that communicate with each other, and with other components, via a bus. The computer system may have any suitable physical form, including but not limited to one or more integrated circuits (ICs), printed circuit boards (PCBs), mobile handheld devices (such as mobile telephones or PDAs), laptop or notebook computers, distributed computer systems, computing grids, or servers.

[0202] The computer system includes one or more processor(s) (e.g., central processing units (CPUs), general purpose graphics processing units (GPGPUs), or quantum processing units (QPUs)) that carry out functions. The processor(s) optionally contains a cache memory unit for temporary local storage of instructions, data, or computer addresses. The processor(s) are configured to assist in execution of computer readable instructions. The computer system may provide functionality for the components depicted in FIGs. 1-14 as a result of the processor(s) executing non-transitory, processor-executable instructions embodied in one or more tangible computer-readable storage media. The computer-readable media may storeWSGR Attorney Docket No. 65297-702.601 software that implements particular embodiments, and the processor(s) may execute the software. Memory may read the software from one or more other computer-readable media or from one or more other sources through a suitable interface, such as a network interface. The software may cause processor(s) to carry out one or more processes or one or more steps of one or more processes described or illustrated herein. Carrying out such processes or steps may include defining data structures stored in memory and modifying the data structures as directed by the software.

[0203] In addition or as an alternative, the computer system may provide functionality as a result of logic hardwired or otherwise embodied in a circuit, which may operate in place of or together with software to execute one or more processes or one or more steps of one or more processes described or illustrated herein. Reference to software in this disclosure may encompass logic, and reference to logic may encompass software. Moreover, reference to a computer-readable medium may encompass a circuit (such as an IC) storing software for execution, a circuit embodying logic for execution, or both, where appropriate. The present disclosure encompasses any suitable combination of hardware, software, or both.

[0204] Those of skill in the art will appreciate that the various illustrative logical blocks, modules, circuits, and algorithm steps described in connection with the embodiments disclosed herein may be implemented as electronic hardware, computer software, or combinations of both. To clearly illustrate this interchangeability of hardware and software, various illustrative components, blocks, modules, circuits, and steps have been described above generally in terms of their functionality.

[0205] The various illustrative logical blocks, modules, and circuits described in connection with the embodiments disclosed herein may be implemented or performed with a general purpose processor, a digital signal processor (DSP), an application specific integrated circuit (ASIC), a field programmable gate array (FPGA) or other programmable logic device, discrete gate or transistor logic, discrete hardware components, or any combination thereof designed to perform the functions described herein. A general purpose processor may be a microprocessor, but in the alternative, the processor may be any conventional processor, controller, microcontroller, or state machine. A processor may also be implemented as a combination of computing devices, e.g., a combination of a DSP and a microprocessor, a plurality of microprocessors, one or more microprocessors in conjunction with a DSP core, or any other such configuration.

[0206] The steps of a method or algorithm described in connection with the embodiments disclosed herein may be embodied directly in hardware, in a software module executed byWSGR Attorney Docket No. 65297-702.601 one or more processor(s), or in a combination of the two. A software module may reside in RAM memory, flash memory, ROM memory, EPROM memory, EEPROM memory, registers, hard disk, a removable disk, a CD-ROM, or any other form of storage medium known in the art. An exemplary storage medium is coupled to the processor such that the processor can read information from, and write information to, the storage medium. In the alternative, the storage medium may be integral to the processor. The processor and the storage medium may reside in an ASIC. The ASIC may reside in a user terminal. In the alternative, the processor and the storage medium may reside as discrete components in a user terminal.

[0207] In accordance with the description herein, suitable computing devices include, by way of non-limiting examples, server computers, desktop computers, laptop computers, notebook computers, netbook computers, netpad computers, handheld computers, Internet appliances, mobile smartphones, and tablet computers. Those of skill in the art will also recognize that select televisions, video players, and digital music players with optional computer network connectivity are suitable for use in the system described herein. Suitable tablet computers, in various embodiments, include those with booklet, slate, and convertible configurations, known to those of skill in the art.

[0208] In some embodiments, the computing device includes an operating system configured to perform executable instructions. The operating system is, for example, software, including programs and data, which manages the device’s hardware and provides services for execution of applications. Those of skill in the art will recognize that suitable server operating systems include, by way of non-limiting examples, FreeBSD, OpenBSD, NetBSD, Linux, Apple Mac OS X Server, Oracle Solaris, Windows Server, and Novell NetWare. Those of skill in the art will recognize that suitable personal computer operating systems include, by way of nonlimiting examples, Microsoft Windows, Apple Mac OS X, UNIX, and UNIX-like operating systems such as GNU / Linux. In some embodiments, the operating system is provided by cloud computing.Non-transitory Computer Readable Storage Medium

[0209] In some embodiments, the platforms, systems, media, and methods disclosed herein include one or more non-transitory computer readable storage media encoded with a program including instructions executable by the operating system of an optionally networked computing device. In further embodiments, a computer readable storage medium is a tangible component of a computing device. In still further embodiments, a computer readable storageWSGR Attorney Docket No. 65297-702.601 medium is optionally removable from a computing device. In some embodiments, a computer readable storage medium includes, by way of non-limiting examples, CD-ROMs, DVDs, flash memory devices, solid state memory, magnetic disk drives, magnetic tape drives, optical disk drives, distributed computing systems including cloud computing systems and services, and the like. In some cases, the program and instructions are permanently, substantially permanently, semi-permanently, or non-transitorily encoded on the media.Computer Program

[0210] In some embodiments, the platforms, systems, media, and methods disclosed herein include at least one computer program, or use of the same. A computer program includes a sequence of instructions, executable by one or more processor(s) of the computing device’s CPU, written to perform a specified task. Computer readable instructions may be implemented as program modules, such as functions, objects, Application Programming Interfaces (APIs), computing data structures, and the like, that perform particular tasks or implement particular abstract data types. In light of the disclosure provided herein, those of skill in the art will recognize that a computer program may be written in various versions of various languages.

[0211] The functionality of the computer readable instructions may be combined or distributed as desired in various environments. In some embodiments, a computer program comprises one sequence of instructions. In some embodiments, a computer program comprises a plurality of sequences of instructions. In some embodiments, a computer program is provided from one location. In other embodiments, a computer program is provided from a plurality of locations. In various embodiments, a computer program includes one or more software modules. In various embodiments, a computer program includes, in part or in whole, one or more web applications, one or more mobile applications, one or more standalone applications, one or more web browser plug-ins, extensions, add-ins, or add-ons, or combinations thereof.Web Application

[0212] In some embodiments, a computer program includes a web application. In light of the disclosure provided herein, those of skill in the art will recognize that a web application, in various embodiments, utilizes one or more software frameworks and one or more database systems. In some embodiments, a web application is created upon a software framework such as Microsoft.NET or Ruby on Rails (RoR). In some embodiments, a web application utilizesWSGR Attorney Docket No. 65297-702.601 one or more database systems including, by way of non-limiting examples, relational, nonrelational, object oriented, associative, XML, and document oriented database systems. In further embodiments, suitable relational database systems include, by way of non-limiting examples, Microsoft SQL Server, mySQL, and Oracle. Those of skill in the art will also recognize that a web application, in various embodiments, is written in one or more versions of one or more languages. A web application may be written in one or more markup languages, presentation definition languages, client-side scripting languages, server-side coding languages, database query languages, or combinations thereof. In some embodiments, a web application is written to some extent in a markup language such as Hypertext Markup Language (HTML), Extensible Hypertext Markup Language (XHTML), or extensible Markup Language (XML). In some embodiments, a web application is written to some extent in a presentation definition language such as Cascading Style Sheets (CSS). In some embodiments, a web application is written to some extent in a client-side scripting language such as Asynchronous JavaScript and XML (AJAX), Flash ActionScript, JavaScript, or Silverlight. In some embodiments, a web application is written to some extent in a server-side coding language such as Active Server Pages (ASP), ColdFusion, Perl, Java, JavaServer Pages (JSP), Hypertext Preprocessor (PHP), Python, Ruby, Tel, Smalltalk, WebDNA, or Groovy. In some embodiments, a web application is written to some extent in a database query language such as Structured Query Language (SQL). In some embodiments, a web application integrates enterprise server products such as IBM Lotus Domino. In some embodiments, a web application includes a media player element. In various further embodiments, a media player element utilizes one or more of many suitable multimedia technologies including, by way of non-limiting examples, Adobe Flash, HTML 5, Apple QuickTime, Microsoft Silverlight, Java, and Unity.Mobile Application

[0213] In some embodiments, a computer program includes a mobile application provided to a mobile computing device. In some embodiments, the mobile application is provided to a mobile computing device at the time it is manufactured. In other embodiments, the mobile application is provided to a mobile computing device via the computer network described herein.

[0214] In view of the disclosure provided herein, a mobile application is created by techniques known to those of skill in the art using hardware, languages, and development environments known to the art. Those of skill in the art will recognize that mobileWSGR Attorney Docket No. 65297-702.601 applications are written in several languages. Suitable programming languages include, by way of non-limiting examples, C, C++, C#, Objective-C, Java, JavaScript, Pascal, Object Pascal, Python, Ruby, VB.NET, WML, and XHTML / HTML with or without CSS, or combinations thereof.

[0215] Suitable mobile application development environments are available from several sources. Commercially available development environments include, by way of non-limiting examples, AirplaySDK, alcheMo, Appcelerator, Celsius, Bedrock, Flash Lite, .NET Compact Framework, Rhomobile, and WorkLight Mobile Platform. Other development environments are available without cost including, by way of non-limiting examples, Lazarus, MobiFlex, MoSync, and Phonegap. Also, mobile device manufacturers distribute software developer kits including, by way of non-limiting examples, iPhone and iPad (iOS) SDK, Android SDK, BlackBerry SDK, BREW SDK, Palm OS SDK, Symbian SDK, webOS SDK, and Windows Mobile SDK.Standalone Application

[0216] In some embodiments, a computer program includes a standalone application, which is a program that is run as an independent computer process, not an add-on to an existing process, e.g., not a plug-in. Those of skill in the art will recognize that standalone applications are often compiled. A compiler is a computer program(s) that transforms source code written in a programming language into binary object code such as assembly language or machine code. Suitable compiled programming languages include, by way of non-limiting examples, C, C++, Objective-C, COBOL, Delphi, Eiffel, Java, Lisp, Python, Visual Basic, and VB.NET, or combinations thereof. Compilation is often performed, at least in part, to create an executable program. In some embodiments, a computer program includes one or more executable complied applications.Software Modules

[0217] In some embodiments, the platforms, systems, media, and methods disclosed herein include software, server, and / or database modules, or use of the same. In view of the disclosure provided herein, software modules are created by techniques known to those of skill in the art using machines, software, and languages known to the art. The software modules disclosed herein are implemented in a multitude of ways. In various embodiments, a software module comprises a file, a section of code, a programming object, a programming structure, a distributed computing resource, a cloud computing resource, or combinationsWSGR Attorney Docket No. 65297-702.601 thereof. In further various embodiments, a software module comprises a plurality of files, a plurality of sections of code, a plurality of programming objects, a plurality of programming structures, a plurality of distributed computing resources, a plurality of cloud computing resources, or combinations thereof. In various embodiments, the one or more software modules comprise, by way of non-limiting examples, a web application, a mobile application, a standalone application, and a distributed or cloud computing application. In some embodiments, software modules are in one computer program or application. In other embodiments, software modules are in more than one computer program or application. In some embodiments, software modules are hosted on one machine. In other embodiments, software modules are hosted on more than one machine. In further embodiments, software modules are hosted on a distributed computing platform such as a cloud computing platform. In some embodiments, software modules are hosted on one or more machines in one location. In other embodiments, software modules are hosted on one or more machines in more than one location.Databases

[0218] In some embodiments, the platforms, systems, media, and methods disclosed herein include one or more databases, or use of the same. In view of the disclosure provided herein, those of skill in the art will recognize that many databases are suitable for storage and retrieval of, by way of examples, image, cell state, protocol, and culture condition information. In various embodiments, suitable databases include, by way of non-limiting examples, relational databases, non-relational databases, object-oriented databases, object databases, entity -relationship model databases, associative databases, XML databases, document-oriented databases, and graph databases. Further non-limiting examples include SQL, PostgreSQL, MySQL, Oracle, DB2, Sybase, and MongoDB. In some embodiments, a database is Internet-based. In further embodiments, a database is web-based. In still further embodiments, a database is cloud computing based. In a particular embodiment, a database is a distributed database. In other embodiments, a database is based on one or more local computer storage devices.Tech-Enabled Therapeutics (TET) Platform Architecture

[0219] In some embodiments, the present disclosure provides a tech-enabled therapeutics (TET) platform that can utilize next generation transdermal smart patches to deliver drugs with improved efficacy and tolerability. The TET platform can work with ultra-low powerWSGR Attorney Docket No. 65297-702.601 custom microcircuitry embedded in the transdermal smart patch that can track usage, connect to the cloud, and enable immediate interventions by caregivers with real time alerts when a dosage is missed.

[0220] This proactive health, wearable solution has massive opportunity to protect quality of life with preventative interventions, while building the first large-scale database with direct measurement of medication dosing patterns. Big data analytics may provide new insights on the effects of dosing patterns on treatment outcomes, impacting pharmaceutical formulations as well as clinical and prescribing practices.

[0221] The TET platform may enhance healthcare outcomes through a combination of innovative technology, data integration, and user-centric applications. The operation of the TET platform may depend on the interaction between smart transdermal smart patches, a cloud-based infrastructure (or a cloud platform), and client application platforms (or user applications).

[0222] In some embodiments, a TET smart patch may comprise or operatively couple to one or more sensors. In some embodiments, a TET smart patch may comprise or operatively couple to one or more sensors and one or more signaling modules. In some embodiments, a TET smart patch may comprise or operatively couple to one or more sensors and a short- range wireless signals low energy radio (LER) module. The one or more sensors may detect a characteristic of the TET smart patch. The one or more sensors may detect a status or state of the TET smart patch. In some embodiments, the state of the smart patch can comprise whether the smart patch has been unpackaged, applied, and / or remains in place.

[0223] In some embodiments, one or more sensors of a TET smart patch may activate in response to a package surrounding the TET smart patch or attached to the TET smart patch being manipulated or opened. In some embodiments, one or more sensors of the TET smart patch can be activated when a seal of a packaging surrounding the TET smart patch or attached to the TET smart patch is broken. In some embodiments, the TET smart patch can complete an electric circuit with a low-energy electrical current when in the packaging. In some embodiments, manipulating one or more parts of the packaging, like breaking a seal, peeling back a portion of the package, ripping or poking one or more parts of the package, or disconnecting a part of the package, for example, can activate the one or more sensors. The sensors can be, for example, light sensors, electricity sensors, pressure sensors, infrared sensors, sound sensors, ultrasound sensors, gas sensors, capacitive sensors, humidity sensors, touch sensors, temperature sensors, magnetic field sensors, resistive sensors, or any combination thereof.WSGR Attorney Docket No. 65297-702.601

[0224] In some embodiments, the smart patch may communicate data that is related to the state of the smart patch, to the cloud platform. In some embodiments, the data may be communicated to the cloud platform directly via a community network. In some embodiments, the data may be communicated using the BLE module. In some embodiments, the data may be communicated to the cloud platform indirectly through a paired smartphone application.

[0225] In some embodiments, the TET patch may comprise a processor. In some embodiments, the processor can perform analytics or calculations on data from one or more sensors of the TET patch. In some embodiments, the processor can perform statistical analysis on data from one or more sensors of the TET patch. In some cases, the statistical analysis can include finding averages of one or more data points from the one or more sensors of the TET patch. In some embodiments, the processor can aggregate data from the one or more sensors. In some embodiments, the processor can compare one or more individual pieces of data from the one or more sensors to an average or other statistical value of an aggregation of data from the one or more sensors.

[0226] In some embodiments, the processor of the TET patch may not contain any personally identifying health information. In some embodiments, the TET patch may not be labeled or otherwise contain any identifying information of the patient. In some embodiments, the TET patch can de-identify data from the one or more sensors.

[0227] In some embodiments, the cloud platform may link the smart patch data with prescription information for each patient, providing a complete view of the patient’s adherence pattern in real time. In some embodiments, prescription information may include medication identifying information, medication dosage, medication timing, or medication interactions, or any combination thereof.

[0228] In some embodiments, additional prescription information may be gathered through connections to provider systems. In some embodiments, additional prescription information may be gathered through connections to pharmacy systems. In some embodiments, additional prescription information may be gathered through connections to provider and pharmacy systems, e.g., using standard industry protocols. In some embodiments, the smart patch data, the prescription information, or the additional prescription information, or any combination thereof can be integrated into the cloud platform, ensuring that full medication regimens are up-to-date and personalized for each patient.

[0229] In some embodiments, the smart patch data, the prescription information, and the additional prescription information may undergo data processing. In some embodiments, theWSGR Attorney Docket No. 65297-702.601 smart patch data, the prescription information, and the additional prescription information may undergo cleansing, standardization, or encryption, or any combination thereof. In some embodiments, the smart patch data, the prescription information, and the additional prescription information may undergo data processing in the cloud platform. In some embodiments, the smart patch data, the prescription information, and the additional prescription information may be managed to facilitate data processing, storage, or analytics, or any combination thereof.

[0230] In some embodiments, the user applications may comprise smartphone applications and / or loT applications. In some embodiments, the user applications may provide information concerning the smart patch data, or the prescription information to one or more persons other than the patient. In some embodiments, the user applications may provide patients and their care circles (e.g., family members, caregivers, pharmacy, physician, etc.) with access to smart patch status / state and replacement schedules. In some embodiments, the user applications may offer interactive features such as medication reminders, communication tools, or real-time updates on adherence across the patient’s entire medication regimen, or any combination thereof.

[0231] In some embodiments, the TET platform may utilize an analytics engine (FIG. 15) to aggregate collected data. In some embodiments, the analytics engine of the TET platform may analyze prescription and / or medication schedule data. In some embodiments, the analytics engine of the TET platform may generate insights into patient behavior at a personal and / or community level. In some embodiments, the insights may allow real-time intervention for each individual level before a missed dose becomes problematic.

[0232] In some embodiments, the TET platform can send notifications to the patients or persons other than the patient. In some embodiments, the TET platform can send reporting notifications to the patient or persons other than the patient. In some embodiments, the TET platform may comprise reporting tools that can provide patients, caregivers, and healthcare providers with information. The information can include detailed adherence reports, facilitating continuous care improvements and accurate measures for cost-of-care models.

[0233] In some embodiments, notifications can comprise push notifications, text messages, calls, emails, banners, in-app alerts, voice alerts, audio tones, spoken alerts, or other sounds, visual signals, light signals, vibration signals such as vibration of one or more technological devices, electrical current signals across the skin or a device, or physical manipulation of one or more objects.WSGR Attorney Docket No. 65297-702.601

[0234] In some embodiments, notifications can be provided for misuse of the smart patch, misuse of one or more medications, one or more missed medication schedules, application of too many smart patches, application of too few smart patches, application of one or more incorrectly medicated smart patches, application of one or more expired medication smart patches, application of one or more defective smart patches, application of one or more smart patches to an incorrect area of the body, application of one or more smart patches for a time period that is too short, application or one or more smart patches for a time period that is too long, accidental detachment of one or more smart patches from the skin, intentional detachment of one or more smart patches from the skin, incomplete application of one or more smart patches, damage to one or more smart patches, application of one or more smart patches with incorrect dosage of medication, application of one or more smart patches with incomplete or incorrect accompanying validation or security information, or another type of notification.

[0235] In some embodiments, notifications can be provided to authorized users. Authorized users can include relatives of the patient, friends of the patient, or care providers of the patient. Care providers of the patient can include medical personnel such as the patient’s physician team, at-home care team, nursing team, nursing home staff, or other healthcare worker(s).

[0236] In some embodiments of the TET platform, all operations can be compliant with HIPAA and other relevant regulations. Patient data can be encrypted throughout its lifecycle, with decryption keys managed securely to maintain confidentiality.

[0237] In some embodiments, the TET platform can aggregate data of one or more patients from each patient’s TET system. In some cases, the TET platform can aggregate and deidentify data. In some cases, the TET platform can aggregate previously de-identified data. In some embodiments, the TET platform can process aggregated data to determine one or more population-level trends or data points. In some embodiments, the one or more populationlevel trends or data points can concern population-level data in areas such as, for example, medication lateness, missed doses, or smart patch removal rates in various populations. In some embodiments, the one or more population-level trends or data points can concern population-level data in areas such as, for example, epidemiological data derived from medication or other patient data collected by the TET platform.

[0238] In some embodiments, the TET platform can be integrated with one or more biometric applications or biometric devices. In some embodiments, TET platform data can be analyzed together with data from one or more biometric applications or biometric devices. In someWSGR Attorney Docket No. 65297-702.601 embodiments, aggregated data gathered by the TET platform can be integrated with aggregated data from one or more biometric applications or biometric devices.

[0239] In some embodiments, the device layer of the TET platform does not store or contain any personally identifiable information. In some embodiments, the device layer of the TET platform does not output any personally identifiable information. In some embodiments, the device layer of the TET platform does not process any personally identifiable information. In some embodiments, the cloud platform does not receive any personally identifiable information from the device layer. In some embodiments, the sidewalk network does not receive any personally identifiable information from the TET patch of the device layer. In some embodiments, the loT Core of the cloud platform does not receive or process any personally identifiable information from the device layer.

[0240] In some embodiments, the TET platform architecture may be scalable, ensuring it can adapt to evolving healthcare needs and technological advancements. In some embodiments, data access and integration may be metadata driven.

[0241] As shown in FIG. 15, the TET platform may comprise multiple technologies or modules to facilitate smart patch monitoring (1500). The TET platform may comprise a device layer / module (1501). In some embodiments, the device layer may comprise the transdermal smart patch (TET smart patch) (1502) having an embedded System-on-a-Chip (SoC). In some embodiments, the SoC can be integrated with one or more sensors to monitor the smart patch status. In some embodiments, the TET smart patch may further comprise a battery. In some embodiments, the battery can be an integrated thin-film flexible printable battery. In some embodiments, the battery may supply power to the SoC.

[0242] In some embodiments, the battery may enter a low-power mode. In some embodiments, the battery may enter a low-power mode as a result of communication from the communication subsystem of the TET smart patch. In some embodiments, the battery may enter a low-power mode as a result of a communication from a cloud module. In some embodiments, the battery may enter a low-power mode in response to a signal from one or more sensors. In some embodiments, the battery can enter a low-power mode to preserve battery and extend battery life. In some embodiments, the battery can enter a low-power mode as a result of a signal for a change of the TET smart patch from work mode to sleep or hibernation mode. In some embodiments, the battery may exit a low-power mode. In some embodiments, the battery may exit a low-power mode as a result of communication from the communication subsystem of the TET smart patch. In some embodiments, the battery may exit a low-power mode as a result of a communication from a cloud module. In someWSGR Attorney Docket No. 65297-702.601 embodiments, the battery may exit a low-power mode in response to a signal from one or more sensors. In some embodiments, the battery can exit a low-power mode to preserve battery and extend battery life. In some embodiments, the battery can exit a low-power mode as a result of a signal for a change of the TET smart patch from sleep or hibernation mode to work mode.

[0243] In some embodiments, the SoC may comprise a microprocessor. In some embodiments, the microprocessor may have programming responsible for sensor data collection, storage, or communication, or any combination thereof. In some embodiments, the chip can be made from a device from Silicon Laboratories (SiLabs) or Nordic Semiconductor (Nordic). In some embodiments, the TET smart patch may communicate to a network. In some embodiments, communication to and from the smart patch may take place using the short-range wireless signals low energy radio (LER) protocol. In some embodiments, the TET smart patch may communicate using near-field communication (NFC) signals, broadband, narrow band-internet of Things (NB-IoT), radio signals, WLAN, cellular signals, or a combination thereof. In some embodiments, the communication may take place in the signal range of about 2.4GHz to about 2.5GHz.

[0244] In some embodiments, the TET chip may further comprise a connection mechanism to a community network (FIG. 15). In some embodiments, the community network may allow signaling between one or more devices in an area, e.g., long-range encrypted community network (1503). In some embodiments, the TET chip may use a cascading set of connection options that use the patient’s or other nearby mobile phone. In some embodiments, messages from each communication path may be securely moved into different queues in the cloud environment (1518). In some embodiments, the data may aggregate. In some embodiments, the aggregated data can be separated from downstream environments. In some embodiments, additional communication channels can be added.

[0245] In some embodiments, the TET platform may further comprise a cloud module (1518). The cloud module (1518) may further comprise one or more AWS cloud services. In some embodiments, the AWS cloud services may comprise managed services. In some embodiments, managed services may comprise, for example, AWS loT Core (1505), Lambda (1510), DynamoDB© (1506), Flink© (1508), or other AWS cloud services. In some embodiments, the AWS cloud module (1518) may perform data processing and storage. In some cases, the data processing and storage may be performed in a HIPAA-compliant manner. In some embodiments, the cloud services may be portable. In some embodiments, data may be input to the AWS loT Core (1505). In some embodiments, raw data may beWSGR Attorney Docket No. 65297-702.601 moved and / or stored in the cloud module (1518). In some embodiments, AWS Lambda (1510) functions may move raw data to a DynamoDB object store (1506). In some cases, this movement of raw data may trigger one or more additional status updates to downstream systems. In some cases, the one or more additional status updates may be output from the cloud module (1518) and input to data providers, an end-user application, or an analytics module (FIG. 15). In some cases, the one or more additional status outputs may be received as inputs by one or more downstream applications within the cloud module. In some embodiments, the one or more downstream applications within the cloud module may comprise AWS AppSync (1512) or AWS Simple Notification Service (SNS) (1511), or both. In some embodiments, AWS AppSync (1512) may facilitate data updates in real time to user applications with open sessions. In some embodiments, the data updates may facilitate interaction by the user with a GUI. In some embodiments, AWS SNS (1511) may receive and process alert and notification messages in response to various planned and detected events. In some embodiments, the user may interact with the alert and notification messages on a GUI. In some cases, the planned and detected events can comprise a medication schedule management event, a medication regimen completion event, a medication change event, or a communication event, or any combination thereof. In some embodiments, the AWS cloud services module (1518) may further comprise AWS Cognito (1507). In some embodiments, AWS Cognito (1507) may manage user account details. In some cases, AWS Cognito (1507) may process user login and authentication. In some cases, AWS Cognito (1507) may store security information. In some cases, AWS Cognito (1507) may process user login and authentication and may store security information. In some embodiments, the application code may be updated to cause the AWS cloud module (1518) to perform functions comprising enforcing updated data security measures.

[0246] In some embodiments, notifications can comprise push notifications, text messages, calls, emails, banners, in-app alerts, voice alerts, audio tones, spoken alerts, or other sounds, visual signals, light signals, vibration signals such as vibration of one or more technological devices, electrical current signals across the skin or a device, or physical manipulation of one or more objects.

[0247] In some embodiments, notifications can be provided for misuse of the smart patch, misuse of one or more medications, one or more missed medication schedules, application of too many smart patches, application of too few smart patches, application of one or more incorrectly medicated smart patches, application of one or more expired medication smart patches, application of one or more defective smart patches, application of one or more smartWSGR Attorney Docket No. 65297-702.601 patches to an incorrect area of the body, application of one or more smart patches for a time period that is too short, application or one or more smart patches for a time period that is too long, accidental detachment of one or more smart patches from the skin, intentional detachment of one or more smart patches from the skin, incomplete application of one or more smart patches, damage to one or more smart patches, application of one or more smart patches with incorrect dosage of medication, application of one or more smart patches with incomplete or incorrect accompanying validation or security information, or another type of notification.

[0248] In some embodiments, notifications can be provided to authorized users. Authorized users can include relatives of the patient, friends of the patient, or care providers of the patient. Care providers of the patient can include medical personnel such as the patient’s physician team, at-home care team, nursing team, nursing home staff, or other healthcare worker(s).

[0249] In some embodiments, the cloud module (1518) may output data to one or more enduser applications (1514). The cloud module may output the data to one or more end-user applications using one or more data exchange applications, for example AppSync (1512). The one or more data exchange applications receive input comprising data from the cloud module (1518), and process the data for output to one or more end-user applications (1514). The one or more end-user applications (1514) can comprise, for example, one or more software applications. In some embodiments, the one or more data exchange applications receive input comprising relevant user data. In some embodiments, the relevant user data is processed by the data exchange applications into a data form suitable for output through authenticated connections. In some embodiments, the one or more data exchange applications may be configured to automatically output updates and / or notifications to the one or more end-user applications (1514) as changes are made on the server. In some cases, these output updates and / or notifications may comprise receive real-time status updates within the one or more end-user applications (1514). In some embodiments, the output updates and / or notifications to the one or more end-user applications (1514) can comprise, for example, whether a TET smart patch is online or offline, whether a medication schedule has not been completed, whether one or more medications have not been indicated as taken, whether one or more medications have been indicated as taken late, or whether a medication routine has been completed, or any combination thereof. In some embodiments, the user can interact with a notification and / or output update using a GUI.WSGR Attorney Docket No. 65297-702.601

[0250] In some embodiments, notifications can comprise push notifications, text messages, calls, emails, banners, in-app alerts, voice alerts, audio tones, spoken alerts, or other sounds, visual signals, light signals, vibration signals such as vibration of one or more technological devices, electrical current signals across the skin or a device, or physical manipulation of one or more objects.

[0251] In some embodiments, notifications can be provided for misuse of the smart patch, misuse of one or more medications, one or more missed medication schedules, application of too many smart patches, application of too few smart patches, application of one or more incorrectly medicated smart patches, application of one or more expired medication smart patches, application of one or more defective smart patches, application of one or more smart patches to an incorrect area of the body, application of one or more smart patches for a time period that is too short, application or one or more smart patches for a time period that is too long, accidental detachment of one or more smart patches from the skin, intentional detachment of one or more smart patches from the skin, incomplete application of one or more smart patches, damage to one or more smart patches, application of one or more smart patches with incorrect dosage of medication, application of one or more smart patches with incomplete or incorrect accompanying validation or security information, or another type of notification.

[0252] In some embodiments, notifications can be provided to authorized users. Authorized users can include relatives of the patient, friends of the patient, or care providers of the patient. Care providers of the patient can include medical personnel such as the patient’s physician team, at-home care team, nursing team, nursing home staff, or other healthcare worker(s).

[0253] In some embodiments, the one or more data exchange applications may further comprise a query construction and object retrieval module. For example, AppSync (1512) uses a GraphQL-based service that manages query construction and object retrieval. In some embodiments, the query construction and object retrieval module may authenticate access and package data for transport to the one or more end user applications. In some embodiments, the query construction and object retrieval module can allow uniform access to a central database by internal cloud users and external application users.

[0254] In some embodiments, one or more data exchange applications, for example, AppSync (1512), may deliver data to client applications as it exists in a central database. In some cases, the data can be delivered without applying additional data processing. In some cases, the data delivery can comprise delivering encrypted data values without decryption. InWSGR Attorney Docket No. 65297-702.601 some cases, one or more data exchange applications may perform decryption using an enduser application (1514) or a cloud-based Lambda function (1510). In some embodiments, the user can interact with the data being delivered using a GUI displaying the data being delivered.

[0255] In some embodiments, a cloud module may further comprise a serverless computing service, for example AWS Lambda (1510). In some cases, the serverless computer service may be used for running backend processes without requiring provisioning or managing servers. In some embodiments, the serverless computing service may process incoming loT data, handle event detection, manage notification delivery, or trigger data ingestion routines across the environment, or any combination thereof. In some cases, serverless computing service algorithms, such as Lambda (1510), may be written in Python or TypeScript. and In some cases, serverless computing service algorithms, such as Lambda (1510), can be executed by various functional ids. In some cases, the ids can mimic internal operational users. In some cases, the ids can have roles and privileges granting access to only those resources necessary for specific executions. For example, an id running a Lambda function that moves messages from the loT Core (1505) to Dynamo DB (1506) may not have the same privileges as an id that sends a notification or alert.

[0256] In some embodiments, the cloud module may further comprise an identity module, for example AWS Cognito (1507). In some embodiments, the identity module can process user login and authentication data. In some embodiments, the identity module can create accounts, reset passwords, or manage two factor authentication, or any combination thereof. In some embodiments, the identity module can further process biometric sign-ins. In some cases, the biometric sign-ins can comprise, for example, fingerprint sign-ins, voice recognition sign-ins, facial recognition sign-ins like FacelD, or any combination thereof. In some embodiments, the identity module can integrate with third-party identity providers. In some cases, the identity module can store additional information outside of the application-level data model. In some cases, this storage can allow separation between application logic and authentication management. In some embodiments, the identity module can store security-related keys and / or device-provided tokens to authorize certain operations. In some cases, the operations can be notifications or alerts. In some cases, the operations can be displayed on a GUI.

[0257] In some embodiments, the cloud module may further comprise a notification module, for example an AWS Simple Notification Service (SNS) (1511). In some embodiments, the notification module can manage the delivery of push notifications to users on different kinds of devices. In some embodiments, the push notifications can be alerts, text messages, images,WSGR Attorney Docket No. 65297-702.601 sounds, vibrations, or any combination thereof. In some cases, the push notifications may be triggered by a serverless computer service, such as one or more Lambda functions (1510). In some cases, the notification module can track device status and / or generate reminder queues.

[0258] In some embodiments, the cloud module may further comprise an analytics module (1509), for example Amazon Flink© (1508), Apache Flink©, or AWS Kinesis Data Analytics©. In some embodiments, the analytics module can perform enterprise-scale stream processing of real time and / or batch data. In some embodiments, the analytics module (1509) may be used for bulk data processes. In some cases, the bulk data processes can operate on entire datasets. In some cases, the datasets can be third-party reference data. In some embodiments, the analytics module (1509) can operate on datasets from metadata. In some cases, the metadata can be from various import sources, targets, formats, or mapping rules, or any combination thereof. In some embodiments, the analytics module (1509) can generate bulk data extracts and / or stage database areas for downstream reporting products. In some embodiments, the analytics module (1509) can operate on one or more integration points.

[0259] In some embodiments, the TET platform may further comprise end-user applications (1514). In some embodiments, end-user applications (1514) may allow users to interact with the TET platform through software or devices, for example mobile applications (1515) or Alexa Echo™ (1517) devices. In some embodiments, the software and devices (1516) produce interactions and reminders related to smart patch status and / or medication routines. In some embodiments, a mobile device may provide a number of additional services unavailable through Alexa Echo™ (1517).

[0260] In some embodiments, the end-user applications (1514) may comprise mobile or stationary device applications. In some cases, the applications can display patient data. In some cases, patient data can comprise smart patch status, receiving reminders about medication schedules, or facilitating communication within a patients circle of care, or any combination thereof. In some embodiments, mobile applications may be built in the Ionic development framework using Typescript. In some embodiments, the mobile applications may comprise a primary user interface layer and a secondary layer. In some embodiments, the secondary layer may provide additional services, e.g., location and LER communication. In some embodiments, the end-user applications may comprise an Amazon Echo™ ecosystem. In some embodiments, the end-user applications may provide voice-ready access to smart patch and medication information, reminders, notifications, or critical alerts, or any combination thereof. In some embodiments, the end-user applications may require cloud connectivity. In some embodiments, when the end-user applications are offline, the end-userWSGR Attorney Docket No. 65297-702.601 applications may provide limited information (e.g., the last known smart patch status). In some embodiments, application data may be updated in real-time. In some embodiments, the patient and a non-patient person can see the updates. In some embodiments, all users in the same care circle can see status changes simultaneously. In some embodiments, reminders and alerts may be directly generated by the application running on a user’s mobile device, e.g., a phone. In some embodiments, reminders and alerts may not be directly generated by the application running on a user’s mobile device, e.g., a phone. In some embodiments, reminders and alerts may be sourced from the cloud.

[0261] In some embodiments, the TET platform may further comprise one or more data providers (1513). In some embodiments, connections to external systems may gather up-to- date information about patient information. In some cases, patient information can comprise patient data, such as a patient’s prescription details, patient prescription scheduling, patient contacts, a smart patch’s status, or a smart patch’s packaging details, or any combination thereof. In some embodiments, the platform may use standard data interchange mechanisms. In some embodiments, the platform can use a modular system to support a variety of transport (e.g., REST) and data (e.g., FHIR) protocols. In some embodiments, data may be imported into and transported through a series of “layers” of the data providers to manage collection, data quality and standardization, and curation for downstream systems.TET Smart patch and loT Connectivity

[0262] FIG. 16 shows a high-level view of the TET smart patch system-on-a-chip (SoC) (1600). In some embodiments, the SoC (1600) may integrate with a signaling ecosystem, for example an NFC system such as a short-range wireless signals ecosystem, for example a low- power short-range wireless signals systems, near-field communication (NFC) signal ecosystems, broadband ecosystems, narrow band-internet of Things (NB-IoT) ecosystems, radio signal ecosystems, WLAN ecosystems, cellular signal ecosystems or any combination thereof. In some embodiments, the signaling ecosystem can be supported by one or more software elements in a cloud and in an end-user application. In some embodiments, the short- range wireless signals ecosystem may be supported by both a long-range encrypted network and a phone application. In some embodiments, the communication may take place in the signal range of about 2.4GHz to about 2.5GHz.

[0263] In some embodiments, the software developed to run on the chip may be configured to interface with external sensors, manage device state, and communicate state messages with a master controller. In some cases, the master controller can be a local controller. In someWSGR Attorney Docket No. 65297-702.601 cases, the master controller can be a local short-range wireless signals master controller. In some cases, the controller can be, for example, a long-range encrypted network Gateway or smartphone with short-range wireless signals enabled.

[0264] In some embodiments, SoC actions may be managed by an application running in the application framework of the device. In some embodiments, SoC may provide an operating system to manage data retrieval, compute tasks, onboard queues, scheduling, object generation, or SQL generation, or any combination thereof.

[0265] In some embodiments, the SoC may be configured with the TET Smart patch application code. In some embodiments, the SoC may be configured with a collection of information unique to each individual chip. In some cases, the unique information may include a BLE Device Address, e.g., a unique 48-bit id, or a set of identifying keys, or both. In some cases, the set of identifying keys may be used during the provisioning and communication process.

[0266] In some embodiments, the SoC may comprise a power state (1602). In some embodiments, after initial configuration, the SoC (1600) may be put into a very low power state, or hibernation power state (1602), to preserve power until it is ready to be used. In some embodiments, the device may be essentially turned off during this time. In some embodiments, information stored at this time may be in a form of non-volatile RAM (NVRAM).

[0267] In some embodiments, the SoC may remain in its hibernation power state (1602) until the patient is ready to apply the transdermal smart patch. In some embodiments, when the smart patch is removed from its packaging, a sensor on the smart patch may detect the removal. In some cases, detection of removal can trigger the power state (1602) to transition from a hibernation power state to a communication power state. In some cases, this transition can be waking the smart patch from a hibernation power state. In some embodiments, the SoC may enter a communication power state (1603) using the communication subsystem (1605). In some embodiments, in a communication power state (1603), the SoC may begin to actively seek a connection to the cloud. In some embodiments, the SoC may comprise one or more sensors. In some cases, the one or more sensors can be configured to determine whether the smart patch is out of the packaging, applied, or removed from application.

[0268] In some embodiments, the SoC can further receive information from one or more sensors (FIG. 16). In some embodiments, the SoC has one or more subsystems to process data from the one or more sensors (1604). In some embodiments, a Sensor GPIO subsystem (1604) can read data from the sensors to determine when to activate the device. In someWSGR Attorney Docket No. 65297-702.601 embodiments, after activation by the GPIO subsystem (1604), a second subsystem can configure the SoC to alternate between sensor monitoring, transmit / receive cycles, and a low power sleep state.

[0269] In some embodiments, the sleep power state (1602) can provide power to volatile RAM to hold dynamic information for transmission to the cloud. In some cases, the overall power demands of the system can be a function of message transmission interval, transmission power, or CPU processing speeds, or any combination thereof.

[0270] In some embodiments, sensor information may be retrieved by code that reads a series of ports (1604). In some cases, the ports can be General Purpose Input / Output (GPIO) ports. In some embodiments, one or more sensors can be connected to one or more ports. In some embodiments, the system may comprise at least two, at least three, at least four, or more than four ports.

[0271] In some embodiments, the SoC may comprise a messaging subsystem (1607). In some embodiments, the messaging subsystem (1607) may perform assembly of message payloads. In some embodiments, the messaging subsystem (1607) may perform persistence functions for messages locally. In some cases, the persistence functions remain until delivery to the cloud has been confirmed by the communication subsystem (1607).

[0272] In some embodiments, a message may comprise the following details: device identifier, device uptime, device battery level, sensor status (e.g., attached, applied, etc.), or device uptime at time of last status change, or any combination thereof.

[0273] In some embodiments, when a connection is active, an attempt may be made to deliver the message using the communication subsystem. In some cases, if delivery succeeds, the message may be discarded. In some cases, if there is no active connection, or the transmission fails for any reason, or both, the message may be stored in a recovery event queue (FIG. 16) to be replayed during some later attempt.

[0274] In some embodiments, the SoC may further comprise an event cache (1606). In some embodiments, the event cache (1606) may further comprise a recovery event queue. In some cases, the recovery event queue can store messages that record each status change. In some embodiments, as a message is added to the recovery queue, the status can be checked by the SoC. In some cases, if the sensor status has not changed, then the earlier message can be replaced with the newer message by the communication subsystem (1605). In other cases, if the status has changed, the new message can be appended to the recovery event queue.

[0275] In some embodiments, the SoC may further comprise a long-range encrypted network to provide a connection-oriented protocol directly to the AWS loT platform. In some cases,WSGR Attorney Docket No. 65297-702.601 the long-range encrypted network of the SoC may enable a device to connect to the cloud without interacting with a user’s phone. In some cases, this connection can bypass the activation and configuration processes.

[0276] In some embodiments, the long-range encrypted connection may be activated at device startup. In some cases, the long-range encrypted connection may be activated if a suitable gateway is within range. In some embodiments, the connection may remain active as long as any gateway is available.

[0277] In some embodiments, the TET smart patch may use a local connection, for example a long-range encrypted connection. In some embodiments, the TET smart patch may periodically check for a local connection, such as a long-range encrypted connection. In some embodiments, if another communication mode has been activated because long-range encrypted was out of range for some time, the TET smart patch may periodically check for a Sidewalk connection automatically.

[0278] In some embodiments, if a long-range encrypted connection is unavailable, the smart patch may begin advertising its presence via signaling. In some cases, the signaling can occur over short-range wireless signals near-field communication (NFC) signals, broadband, narrow band-internet of Things (NB-IoT), radio signals, WLAN, cellular signals, or another signaling method. In some cases, the signaling can occur over short-range wireless signals for a phone-based connection. In some embodiments, the communication may take place in the signal range of about 2.4GHz to about 2.5GHz. In some embodiments, if a suitable phone application is found, the smart patch and phone may use security keys on the phone and on the device to jointly. In some cases, this joint security key use may authenticate that the device and phone application belong to the same user. In some cases, the connection may fail if the devices cannot mutually identify each other.

[0279] In some embodiment, if a phone connection cannot be established, the TET smart patch may fall back to advertising an encrypted payload. In some embodiments, the encrypted payload can be recognizable by the phone application running on any phone in the area. In some cases, one or more phones can smart patch messages to the cloud while being unable to read their payload.

[0280] In some embodiments, in the advertising signaling mode, the SoC may confirm that the message is received by the cloud when a connection is reestablished. In some embodiments, once a connection has been reestablished, the events in the recovery event queue may be replayed to the cloud. In some cases, the events in the recovery event queue of the SoC may be identified and processed as if they were original messages andWSGR Attorney Docket No. 65297-702.601 communication resumes.

[0281] In some embodiments, the SoC may comprise a beacon mode. In some cases, beacon mode can comprise phone applications forwarding information across signaling connections, such as BLE signaling. In some cases, phone applications can form new connections even when they are running in the background, e.g., when they are not the main application on the screen.

[0282] In some embodiments, the application may start manually when a user receives a notification. In some embodiments, the application may start manually when the user opens the device intentionally. In some embodiments, if a phone gets restarted, the application may not be running in the background. In some cases, if a phone gets restarted, the application may start running in the background only when the user receives a notification or opens the device intentionally. In some embodiments, the TET smart patch can remain in an unconnected state after an automatic update or other restart.

[0283] In some embodiments, the smart patch can act as an iBeacon. In some embodiments, an iBeacon can be registered with a phone. In some embodiments, when an iBeacon is registered with a phone, the phone may wake a specific application when the phone comes within range.

[0284] In some embodiments, if a TET smart patch determines that it has not had a connection for some time, it may periodically revert to this iBeacon mode. In some embodiments, if the phone detects the iBeacon, it may start the application. In some embodiments, if the phone detects the iBeacon, a normal connection can be established. In some embodiments, the SoC can ensure connection security with the communication subsystem (FIG. 16). In some embodiments, each message can be transmitted securely from the device to the cloud. In some embodiments, the SoC can ensure that smart patch status data is accurate through the communication and sensor subsystems. In some embodiments, the SOC can prevent incorrect or garbled data injected into the system through the sensor GPIO and communication subsystems.

[0285] In some embodiments, the local connection module, for example a long-range encrypted network, encrypts and validates all connections. In some embodiments, the protocol can be essentially set up like an SSL-based private network tunnel implemented over a BLE network. In some embodiments, message encryption and decryption may be handled entirely by the protocol stack, with all content arriving at a pre-configured endpoint.

[0286] In some embodiments, mobile phone connection security may be handled in the application layers on the SoC and on the phone (FIG. 17). In some cases, the system canWSGR Attorney Docket No. 65297-702.601 comprise application-level security (FIG. 17).

[0287] In some embodiments, a standard BLE connection can be established. In some embodiments, each end of the application can authenticate the other based on the use of presigned trusted certificates as depicted in FIG. 17. In some embodiments, the device certificate may be installed during manufacturing. In some embodiments, the phone application can be delivered to the phone after a successful login. In some embodiments, once the two endpoints have been authenticated, the devices can agree to a shared key that is used to encrypt all messages for the current session (FIG. 17). In some embodiments, if either device fails to recognize the identity of the other, the session can be terminated.

[0288] In some embodiments, when advertising, messages can be encrypted and signed using the pre-installed device certificates. In some cases, encrypted messages can later be decrypted in the cloud. In some embodiments, mobile phones that forward these messages can be rendered unable to read their content. In some embodiments, encrypted advertising messages may be exclusively forwarded to the cloud by devices that support ADV EXT IND and related protocol data units.

[0289] In some embodiments, a user’s private key can be processed into a custom signature using user data (FIG. 17). In some embodiments, the user data can be used to generate one or more authentication certifications. In some embodiments, a signature and certification can be combined to verify certification or verify signature. In some embodiments, the verifications can each result in a binary approval or disapproval of the authentication. In some embodiments, an approval can result in transfer of data from a patient to another user. In some embodiments, a disapproval can result in prevention of data transfer between users. In some cases, one or more hash functions can be used to convert user data into encrypted data. In some cases, the one or more hash functions can be combined with a user’s private key for authentication processing. In some embodiments, a public key can be used to decrypt encrypted signatures, resulting in data transfer.

[0290] In some embodiments, the implementation of the cloud platform can be modularized. In some embodiments, changes can be made to core components without requiring major rewrites across the environment.

[0291] In some cases, one or more messages from one or more TET smart patches may first land in an MQTT endpoint. In some cases, the MQTT endpoint can be configured and managed through the AWS loT Core service. In some cases, each message source may be individually authenticated. In some cases, the authentication can take place using preinstalled device keys or through the phone user’s account, or both.WSGR Attorney Docket No. 65297-702.601

[0292] In some embodiments, each path may target a separate queue. In some cases, each path may result in path variations being handled in isolation. In some embodiments, existing message paths can be scaled independently. In some embodiments, new message paths can be added. In some embodiments, each path can be updated without affecting other paths.

[0293] In some embodiments, messages landing in any queue may be forwarded to a central database, such as DynamoDB, by serverless computing service algorithms, such as an AWS Lambda function. In some cases, advertising messages may be decrypted during this process. In some embodiments, each message entering a central database, such as DynamoDB, can be handled similarly regardless of its source.

[0294] In some embodiments, data storage for both messages and application data may be provided by a central database, for example DynamoDB. In some embodiments, the central database can be a NoSQL object store. In some embodiments, the central database can comprise scalable storage and access speed.

[0295] In some embodiments, each message uploaded to an loT Core may be forwarded to a landing table in a central database, such as DynamoDB. In some embodiments, messages may be monitored in real time for status updates. In some cases, each status change can be recorded as a device event. In some embodiments, if the status is unchanged, the “updatedAf ’ timestamp for the latest device event can be updated. In some embodiments, the device event table can only record changes, not raw events, which may be discarded after some time.

[0296] In some embodiments, each status change may also trigger an update in the device table. In some cases, the device table contains the latest status for the smart patch. In some cases, this table may be monitored to deliver immediate updates when a smart patch is attached or detached.

[0297] In some cases, records might arrive out-of-order if advertising messages were forwarded while the smart patch was offline. In some cases, a new device event may be created to track the history of the device. In some cases, the latest status updates may trigger changes in the device table. In some cases, the advertising events may have already served to keep the device information updated.Data Model

[0298] In some embodiments, the data model can comprise one or more subject areas. In some cases, the data model can comprise four subject areas: electronics, members, integrations, and operations.WSGR Attorney Docket No. 65297-702.601

[0299] In some embodiments, as shown in FIG. 18, the electronics subject area may comprise a plurality of modules that can track device details and messages. In some embodiments, each of the plurality of modules can comprise one or more databases, one or more algorithms, or one or more matrices, or any combinations thereof (FIG. 18).

[0300] In some embodiments, data rates may be on the order of 1 GB per patient per year. In some embodiments, raw messages may be stored for three days. In some embodiments, total data volumes may level off for each patient at closer to 10 MB per patient, or 1 TB for 100,000 active patients.

[0301] In some embodiments, the plurality of modules may comprise the current status details for each TET smart patch as accessed by user applications. In some embodiments, patch manufacturing information may allow links to each TET smart patch and patient, enabling notification and monitoring.

[0302] In some embodiments, notifications can comprise push notifications, text messages, calls, emails, banners, in-app alerts, voice alerts, audio tones, spoken alerts, or other sounds, visual signals, light signals, vibration signals such as vibration of one or more technological devices, electrical current signals across the skin or a device, or physical manipulation of one or more objects.

[0303] In some embodiments, notifications can be provided for misuse of the smart patch, misuse of one or more medications, one or more missed medication schedules, application of too many smart patches, application of too few smart patches, application of one or more incorrectly medicated smart patches, application of one or more expired medication smart patches, application of one or more defective smart patches, application of one or more smart patches to an incorrect area of the body, application of one or more smart patches for a time period that is too short, application or one or more smart patches for a time period that is too long, accidental detachment of one or more smart patches from the skin, intentional detachment of one or more smart patches from the skin, incomplete application of one or more smart patches, damage to one or more smart patches, application of one or more smart patches with incorrect dosage of medication, application of one or more smart patches with incomplete or incorrect accompanying validation or security information, or another type of notification.

[0304] In some embodiments, notifications can be provided to authorized users. Authorized users can include relatives of the patient, friends of the patient, or care providers of the patient. Care providers of the patient can include medical personnel such as the patient’s physician team, at-home care team, nursing team, nursing home staff, or other healthcareWSGR Attorney Docket No. 65297-702.601 worker(s).

[0305] As shown in FIG. 19, in some embodiments the members subject area may comprise a plurality of modules. In some embodiments, the plurality of modules may be linked with one or more authentication modules, for example the AWS Cognito service. In some embodiments, the data fields may be encrypted in place to protect personal health information. In some embodiments, the data fields may be encrypted and decrypted using customer-specific keys shared with the user application and internal cloud systems. In some embodiments, the members subject area may comprise a plurality of databases, algorithms, datasets, matrices, or any combination thereof.

[0306] As shown in FIG. 20, the integrations subject area may comprise a plurality of modules to connect metadata to external data providers (e.g., Epic). In some embodiments, the metadata may be used to manage system level access to third party system APIs and userspecific account access details needed to present information like prescription details to users. In some embodiments, the integrations subject area may comprise a plurality of databases, algorithms, datasets, matrices, or any combination thereof.

[0307] As shown in FIG. 21, in some embodiments, the operations subject area may comprise a plurality of modules that can track application-level operations like job execution schedules, job logging, and administrative edits to patient records. In some embodiments, the plurality of modules can work in concert with one or more authentication databases, for example AWS Cloudwatch and Cloudtrail, which may provide detailed lower-level information. In some embodiments, the operations subject area may comprise a plurality of databases, algorithms, datasets, matrices, or any combination thereof.

[0308] In some embodiments, the main model subject area may comprise some combination of one or more subject areas, such as the operations subject area, integrations subject area, member subject area, electronics subject area, or any combination thereof.

[0309] In some embodiments, mobile platforms may not accept notifications without user permission. In some embodiments, when a user grants permission to the application, a permission token may be generated and stored with user details. In some embodiments, the SNS may retrieve this token when delivering the message.

[0310] In some embodiments, the TET platform may serve as a reminder manager for a patient’s TET smart patch and medication routines. In some embodiments, information about the medication regiment can be shared with a person other than the user, such as with a trusted circle of family members and friends. In some embodiments, the TET platform may track smart patch status. In some embodiments, the TET platform may send increasinglyWSGR Attorney Docket No. 65297-702.601 urgent alerts to all members of a patient’s circle if a smart patch change is missed. In some embodiments, the TET platform may comprise pharmacy prescription information for the smart patch.

[0311] In some embodiments, the application may use a pill-box carousel metaphor to present a patient’s smart patch and medication routine status. In some cases, the carousel metaphor may comprise a setup with columns of the carousel representing different days and each row representing a time of day when a collection of pills should be taken. In some embodiments, the TET smart patch may be represented as a ribbon across the top row, indicating that its use is automatic and extends across many days.

[0312] In some embodiments, the carousel can use color, iconography, or words, or any combination thereof to indicate the current status. In some embodiments, touch screen or voice interfaces can facilitate interactions concerning details of each routine. In some embodiments, each screen may provide easy access to communication tools and alert details.

[0313] In some embodiments, both mobile applications and devices such as loT devices can synchronize with the same AWS cloud backend. In some embodiments, medication schedules, smart patch status, or circle member interactions can be updated to be current across all devices.

[0314] In some cases, the mobile application may be written in TypeScript using the Ionic Framework structure.

[0315] In some cases, data for the mobile application may be retrieved from the cloud. In some cases, the data may be retrieved for example using GraphQL through AppSync. In some embodiments, data elements retrieved from the cloud may be mapped to visual elements on the screen using standard model or view patterns based on style sheets and the Typescript template model. In some embodiments, the user may interact with the data elements using a GUI.

[0316] In some embodiments, data updates may be pushed to the phone from the cloud automatically. In some cases, the updates may enable all users to see the same information at the same time.

[0317] In some embodiments, the mobile application may provide a service layer that operates in the background while the application is off screen. In some embodiments, this layer may manage BLE connectivity using native features implemented in a devicedependent way (e.g., with Swift on iOS devices).

[0318] In some embodiments, connections between the service layer and the user interface layer may be minimized. In some embodiments, the mobile application may display the latestWSGR Attorney Docket No. 65297-702.601 information from a connected smart patch without an internet connection. In some embodiments, the mobile application may comprise a BLE Connection, BLE Advertisement Forwarding, Beacon discovery, or location updates, or any combination thereof. In some embodiments, the mobile application may comprise a separate simple scheduling service that allows developer configuration of certain update intervals.

[0319] In some embodiments, voice or touch commands may trigger interactions directly with the cloud. In some cases, these interactions may trigger Lambda functions running in the cloud that pull information back to the user’s device.

[0320] In some embodiments, all devices can receive alerts when an urgent condition is detected. In some embodiments, all devices can receive alerts for scheduled reminders. In some embodiments, the system may utilize push notifications to alert users of medication times, smart patch application reminders, or any required actions. In some embodiments, the system may present users with urgent alerts designed to override device settings for immediate attention. In some embodiments, interacting with a notification may cause the application to open to a relevant display. In some embodiments, circle members can reach out directly to the patient from the app, using standard phone video calling, text messaging, recorded voice notes, or the Alexa application.

[0321] FIG. 22 shows a non-limiting diagram of an exemplary connectivity configuration for various databases.

[0322] FIG. 23 shows a graphic user interface (GUI) as an exemplary user interface e.g., a home screen of the TET platform. In some embodiments, the GUI may show a notification, e.g., a morning notification from CareMinder. As used herein, CareMinder generically refers to any software-based application allowing a user to interface with a TET platform. In some embodiments, CareMinder comprises a graphic user interface (GUI) that can facilitate interactions of one or more users with a TET platform. In some embodiments, CareMinder can interface with one or more interpersonal contact applications to communicate with one or more people in the patient's care circle. In some embodiments, the GUI may display a settings call menu icon as shown in FIG. 23, for example. In some embodiments, the GUI may display a notification indicator in the as shown, for example, in FIG. 23. In some embodiments, the indicator can show the presence of one or more notices, for example in FIG. 23 displaying two notices. In some embodiments, the user (e.g., Martha) can activate the system by touch activation, voice activation, tapping activation, or any combination thereof, for example the user can tap the screen or say “Alexa, open CareMinder” to activate the system.WSGR Attorney Docket No. 65297-702.601

[0323] FIG. 24 shows an exemplary user interface (a screen) of the TET platform. In some embodiments, the GUI can show pre-configured timeslots (routines) during the day. In some embodiments, the GUI can show a snapshot of one or more days relative to the current day, for example, yesterday, today, and tomorrow with various indications. In some embodiments, the GUI can display across the top of the screen an unbroken ribbon, which can represent the active TET smart patch. In some embodiments, when the ribbon is in yellow, it can indicate it is time to replace the smart patch. In some embodiments, the GUI can show completed routines at one or more times of the day, for example the morning, noon, and evening routines. In some embodiments, in the middle of the screen, the GUI can show, for example, the morning routine is in a certain amount of time, for example 15 minutes. In some embodiments, the GUI can also show the number of remaining smart patches. In some embodiments, a user can tap the screen in the center area to see the details of the routines. In some embodiments, the system can be voiced enabled. In some embodiments, instead of tapping the screen, the user can command the system to act.

[0324] In some embodiments, FIG. 25 shows an exemplary GUI with a plurality of routines. In some embodiments, the GUI can comprise a plurality of columns and rows, like a compartment in a pill box. In some embodiments, the system can store a plurality of routines a day. In some embodiments, the system can track which medication, and how much, is required for each time slot. In some embodiments, graphics can represent realistic shapes and colors for each pill. In FIG. 25, for example, since it is time for the user to change her rivaroxaban smart patch, this is highlighted first. In FIG. 25, for example, the top of the screen shows “next up: change your TET smart patch”. In some embodiments, on the GUI, future details are visible and can scroll vertically if needed. In some embodiments, the GUI can show other routines for other medications, e.g., type of medication, doses each day, medication time, etc. In some embodiments, when the user opens the TET smart patch and applies it, the Cloud can be notified. In some embodiments, when the Cloud is notified, the application can be updated. In some embodiments, the GUI can automatically change without any interaction.

[0325] FIG. 26 shows an exemplary updated GUI when a smart patch is detected. In FIG. 26, for example, the smart patch status indicates new TET smart patch is detected. In some embodiments, the color for the smart patch routine may change, e.g., from yellow to green. In FIG. 26, for example, the next routine is highlighted in yellow, and the icon in the lower right indicates one more reminder. In some embodiments, the details can change dynamically as the user goes through different routines during the day. In FIG. 26, for example, the screenWSGR Attorney Docket No. 65297-702.601 shows the user’s other routines for this Monday morning, both medication to take and the number of pills for each. In some embodiments, the user can complete the regimen and say, “Alexa, I took my medicine” to change the status for each of the routine.

[0326] FIG. 27 shows an exemplary updated GUI when the morning routine is completed. In FIG. 27, for example, Martha has replaced her smart patch, which now shows a green status across the ribbon. In FIG. 27, for example, she has completed her morning routine, as the green check icons indicate. In FIG. 27, the pill box notes the time until the next routine. In FIG. 27 and FIG. 28, for example, there are no active reminders, so that reminder icon shows green. In FIG. 27 and FIG. 28, for example, Martha can say “Alexa, close CareMinder” to put the system to sleep mode when no medications remain to be taken. As shown in FIG. 28, for example, the screen shows no alerts.

[0327] FIG. 29, for example, shows another exemplary GUI e.g., a home screen of the TET platform. In some embodiments, the GUI may show a notification, e.g., a morning notification from CareMinder as shown in FIG. 29. In some embodiments, the GUI may display settings call menu icon in the upper right and a notification indicator in the lower right. In FIG. 29, for example, the indicator shows there are two notices. In some embodiments, the user (e.g., Martha as shown in FIG. 29) can activate the system by voice command or touch command, for example, the user can tap the screen or say “Alexa, open CareMinder” to activate the system.

[0328] FIG. 30 shows another exemplary GUI e.g., a home screen of the TET platform if the morning routine is due. In FIG. 30, for example, the notification icon turned red and the screen shows “Reminder from CareMinder. It’s time to change your TET smart patch. Your morning routine is due”. As shown in FIG. 30, for example, the user (e.g., Martha) can tap the screen or say “Alexa, open CareMinder” to activate the system. In some embodiments, if the user is not ready, they can ask the system to send a reminder later, e.g., say “Alexa, remind me in 15 minutes.”

[0329] FIG. 31 shows another exemplary user interface e.g., a home screen of the TET platform if the morning routine is overdue. As in FIG. 31, for example, the notification icon is red and the screen shows “Second reminder from CareMinder. It’s time to change your TET smart patch. Your morning routine is overdue”. In some embodiments, a circle member can receive a notification on his / her device indicating the user has not checked in. In some embodiments, the user (e.g., Martha as shown in FIG. 31) can tap the screen or say “Alexa, open CareMinder” to activate the system.

[0330] FIG. 32 shows an exemplary GUI when there is an action overdue. In FIG. 32, forWSGR Attorney Docket No. 65297-702.601 example, the TET smart patch ribbon is duplicated for emphasis, and the Morning routine is highlighted in red. In some embodiments, icons like the checkmarks seen on other days can be removed, and most navigation can be disabled to highlight the current need.

[0331] FIG. 33 shows an exemplary screen of a circle member (e.g., Kathy, Martha’s daughter). In some embodiments, the circle member’s screen can show one or more alerts that the user is off schedule for the critical dose medications. In FIG. 33, for example, when Kathy selects the notification, the CareMinder phone application launches, showing the same details seen on Martha’s screen. In FIG. 33, for example, because Martha has enabled Kathy to see her location, Kathy can tell that her mother is at home. In FIG.33, for example, because the applications share information through the cloud, Kathy has access to the same information at the same time that Martha can see it. As shown in FIG. 34, for example, Kathy can contact her mother to make sure everything is ok.

[0332] In some embodiments, an edge device can receive contact data from one or more people in the patient’s care circle. For example, a device such as an Echo can receive video or voice calls. In some embodiments, some circumstances can allow a “drop in” call where approved user or circle member can directly open a connection as shown in FIG. 34. FIG. 34 shows, for example, that Martha receives a video call from Kathy while she is looking at the CareMinder screen. In some embodiments, as shown in FIG. 35, if the user replaces the smart patch, the circle member can receive a notice that the new smart patch is detected. In some embodiments, if the user has not completed a morning routine, the system can send an alert to a member of the patient’s care circle that the patient’s morning routine is overdue. In some cases, the name of the patient can be customized. As shown in FIG. 35, since the user has not completed the morning routine yet, the circle member’s screen shows “mom’s morning routine is overdue”. In some embodiments, if the user replaces the smart patch and completes the routine, the circle member can get a notice that the new smart patch is active and the routine is complete.

[0333] FIG. 36 shows an exemplary screen after the morning routine is complete. As shown in FIG. 36 for example, Martha has replaced her smart patch, which now shows a green status across the ribbon. In FIG. 36 for example, she has completed her morning routine, as the green check icons indicate. In FIG. 36, for example, the pill box can note the time until the next routine. In some embodiments, where there are no active reminders, so the reminder icon can appear green. In FIG. 36, for example, Martha can say “Alexa, close CareMinder” to put the system to sleep mode.

[0334] FIG. 37 shows exemplary GUI displays of the circle member after the user’s morningWSGR Attorney Docket No. 65297-702.601 routine is complete. In FIG. 37, for example, the GUI shows the new TET smart patch is detected and the morning routine is done. Additionally, in FIG. 37, for example, the next GUI display shows the next routine is in 4 hours.

[0335] In some embodiments, a transdermal drug delivery smart patch can comprise a drugcontaining layer; a communication interface; a processor communicatively coupled to the communication interface, wherein the processor can be configured to perform operations comprising: (a) receiving a wireless signal or electric current through the communication interface; and (b) releasing a (e.g., predetermined) amount of drug from the drug-containing layer. In some embodiments, the processor can comprise a system-on-a-chip (SoC). In some embodiments, the SoC can comprise one or more of a messaging subsystem, a sensor subsystem, a power state subsystem, a communication state subsystem, a communication subsystem, a printable battery, or an event cache subsystem, or any combination thereof.

[0336] In some embodiments, the printable battery may enter a low-power mode. In some embodiments, the printable battery may enter a low-power mode as a result of communication from the communication subsystem of the TET smart patch. In some embodiments, the printable battery may enter a low-power mode as a result of a communication from a cloud module. In some embodiments, the printable battery may enter a low-power mode in response to a signal from one or more sensors. In some embodiments, the printable battery can enter a low-power mode to preserve battery and extend battery life. In some embodiments, the printable battery can enter a low-power mode as a result of a signal for a change of the TET smart patch from work mode to sleep or hibernation mode. In some embodiments, the printable battery may exit a low-power mode. In some embodiments, the printable battery may exit a low-power mode as a result of communication from the communication subsystem of the TET smart patch. In some embodiments, the printable battery may exit a low-power mode as a result of a communication from a cloud module. In some embodiments, the printable battery may exit a low-power mode in response to a signal from one or more sensors. In some embodiments, the printable battery can exit a low-power mode to preserve battery and extend battery life. In some embodiments, the printable battery can exit a low-power mode as a result of a signal for a change of the TET smart patch from sleep or hibernation mode to work mode.

[0337] In some embodiments, the communication subsystem can receive data from a cloud server system using the wireless signal or the electric current. In some embodiments, one or more drugs can be loaded on the drug-containing layer. In some embodiments one or more drugs can be lipophilic or hydrophilic. In some embodiments, one or more placebos can beWSGR Attorney Docket No. 65297-702.601 loaded on the drug-containing layer. In some embodiments, the drug-containing layer can comprise a layer of drug-in-adhesive. In some embodiments, the drug-containing layer can comprise a plurality of layers of drug-in-adhesive and a membrane positioned therebetween. In some embodiments, the drug-containing layer can comprise a drug reservoir, an adhesive layer, and a membrane positioned therebetween. In some embodiments, the drug-containing layer can comprise a drug reservoir and an adhesive ring therearound. In some embodiments, the drug-containing layer can comprise a drug-containing microneedle array and an adhesive layer. In some embodiments, the drug-containing layer can comprise one or more excipients that facilitate (i) permeation of the drug through the skin and (ii) drug delivery. In some embodiments, one or more excipients can comprise one or more chemical enhancers. In some embodiments, the wireless signal or the electric current received by the communication interface can be associated with releasing the drug.Computing Systems

[0338] Referring to FIG. 38, a block diagram is shown depicting an exemplary machine that includes a computer system 3800 (e.g., a processing or computing system) within which a set of instructions can execute for causing a device to perform or execute any one or more of the aspects and / or methodologies for static code scheduling of the present disclosure. The components in FIG. 38 are examples only and do not limit the scope of use or functionality of any hardware, software, embedded logic component, or a combination of two or more such components implementing particular embodiments.

[0339] Computer system 3800 may include one or more processors 38038, a memory 3803, and a storage 3808 that communicate with each other, and with other components, via a bus 3840. The bus 3840 may also link a display 3832, one or more input devices 3833 (which may, for example, include a keypad, a keyboard, a mouse, a stylus, etc.), one or more output devices 3834, one or more storage devices 3835, and various tangible storage media 3836. All of these elements may interface directly or via one or more interfaces or adaptors to the bus 3840. For instance, the various tangible storage media 3836 can interface with the bus 3840 via storage medium interface 3826. Computer system 3800 may have any suitable physical form, including but not limited to one or more integrated circuits (ICs), printed circuit boards (PCBs), mobile handheld devices (such as mobile telephones or PDAs), laptop or notebook computers, distributed computer systems, computing grids, or servers.

[0340] Computer system 3800 includes one or more processor(s) 38038 (e.g., centralWSGR Attorney Docket No. 65297-702.601 processing units (CPUs) or general purpose graphics processing units (GPGPUs)) that carry out functions. Processor(s) 38038 optionally contains a cache memory unit 3802 for temporary local storage of instructions, data, or computer addresses. Processor(s) 38038 are configured to assist in execution of computer readable instructions. Computer system 3800 may provide functionality for the components depicted in FIG. 38 as a result of the processor(s) 38038 executing non-transitory, processor-executable instructions embodied in one or more tangible computer-readable storage media, such as memory 3803, storage 3808, storage devices 3835, and / or storage medium 3836. The computer-readable media may store software that implements particular embodiments, and processor(s) 38038 may execute the software. Memory 3803 may read the software from one or more other computer-readable media (such as mass storage device(s) 3835, 3836) or from one or more other sources through a suitable interface, such as network interface 3820. The software may cause processor(s) 38038 to carry out one or more processes or one or more steps of one or more processes described or illustrated herein. Carrying out such processes or steps may include defining data structures stored in memory 3803 and modifying the data structures as directed by the software.

[0341] The memory 3803 may include various components (e.g., machine readable media) including, but not limited to, a random access memory component (e.g., RAM 3804) (e.g., static RAM (SRAM), dynamic RAM (DRAM), ferroelectric random access memory (FRAM), phase-change random access memory (PRAM), etc.), a read-only memory component (e.g., ROM 3805), and any combinations thereof. ROM 3805 may act to communicate data and instructions unidirectionally to processor(s) 38038, and RAM 3804 may act to communicate data and instructions bidirectionally with processor(s) 38038. ROM 3805 and RAM 3804 may include any suitable tangible computer-readable media described below. In one example, a basic input / output system 3806 (BIOS), including basic routines that help to transfer information between elements within computer system 3800, such as during start-up, may be stored in the memory 3803.

[0342] Fixed storage 3808 is connected bidirectionally to processor(s) 38038, optionally through storage control unit 3807. Fixed storage 3808 provides additional data storage capacity and may also include any suitable tangible computer-readable media described herein. Storage 3808 may be used to store operating system 3809, executable(s) 38380, data 383838, applications 38382 (application programs), and the like. Storage 3808 can also include an optical disk drive, a solid-state memory device (e.g., flash-based systems), or a combination of any of the above. Information in storage 3808 may, in appropriate cases, beWSGR Attorney Docket No. 65297-702.601 incorporated as virtual memory in memory 3803.

[0343] In one example, storage device(s) 3835 may be removably interfaced with computer system 3800 (e.g., via an external port connector (not shown)) via a storage device interface 3825. Particularly, storage device(s) 3835 and an associated machine-readable medium may provide non-volatile and / or volatile storage of machine-readable instructions, data structures, program modules, and / or other data for the computer system 3800. In one example, software may reside, completely or partially, within a machine-readable medium on storage device(s) 3835. In another example, software may reside, completely or partially, within processor(s) 38038.

[0344] Bus 3840 connects a wide variety of subsystems. Herein, reference to a bus may encompass one or more digital signal lines serving a common function, where appropriate. Bus 3840 may be any of several types of bus structures including, but not limited to, a memory bus, a memory controller, a peripheral bus, a local bus, and any combinations thereof, using any of a variety of bus architectures. As an example and not by way of limitation, such architectures include an Industry Standard Architecture (ISA) bus, an Enhanced ISA (EISA) bus, a Micro Channel Architecture (MCA) bus, a Video Electronics Standards Association local bus (VLB), a Peripheral Component Interconnect (PCI) bus, a PCI-Express (PCI-X) bus, an Accelerated Graphics Port (AGP) bus, HyperTransport (HTX) bus, serial advanced technology attachment (SATA) bus, and any combinations thereof.

[0345] Computer system 3800 may also include an input device 3833. In one example, a user of computer system 3800 may enter commands and / or other information into computer system 3800 via input device(s) 3833. Examples of an input device(s) 3833 include, but are not limited to, an alpha-numeric input device (e.g., a keyboard), a pointing device (e.g., a mouse or touchpad), a touchpad, a touch screen, a multi-touch screen, a joystick, a stylus, a gamepad, an audio input device (e.g., a microphone, a voice response system, etc.), an optical scanner, a video or still image capture device (e.g., a camera), and any combinations thereof. In some embodiments, the input device is a Kinect, Leap Motion, or the like. Input device(s) 3833 may be interfaced to bus 3840 via any of a variety of input interfaces 3823 (e.g., input interface 3823) including, but not limited to, serial, parallel, game port, USB, FIREWIRE, THUNDERBOLT, or any combination of the above.

[0346] In particular embodiments, when computer system 3800 is connected to network 3830, computer system 3800 may communicate with other devices, specifically mobile devices and enterprise systems, distributed computing systems, cloud storage systems, cloud computing systems, and the like, connected to network 3830. Communications to and fromWSGR Attorney Docket No. 65297-702.601 computer system 3800 may be sent through network interface 3820. For example, network interface 3820 may receive incoming communications (such as requests or responses from other devices) in the form of one or more packets (such as Internet Protocol (IP) packets) from network 3830, and computer system 3800 may store the incoming communications in memory 3803 for processing. Computer system 3800 may similarly store outgoing communications (such as requests or responses to other devices) in the form of one or more packets in memory 3803 and communicated to network 3830 from network interface 3820. Processor(s) 38038 may access these communication packets stored in memory 3803 for processing.

[0347] Examples of the network interface 3820 include, but are not limited to, a network interface card, a modem, and any combination thereof. Examples of a network 3830 or network segment 3830 include, but are not limited to, a distributed computing system, a cloud computing system, a wide area network (WAN) (e.g., the Internet, an enterprise network), a local area network (LAN) (e.g., a network associated with an office, a building, a campus or other relatively small geographic space), a telephone network, a direct connection between two computing devices, a peer-to-peer network, and any combinations thereof. A network, such as network 3830, may employ a wired and / or a wireless mode of communication. In general, any network topology may be used.

[0348] Information and data can be displayed through a display 3832. Examples of a display 3832 include, but are not limited to, a cathode ray tube (CRT), a liquid crystal display (LCD), a thin film transistor liquid crystal display (TFT-LCD), an organic liquid crystal display (OLED) such as a passive-matrix OLED (PMOLED) or active-matrix OLED (AMOLED) display, a plasma display, and any combinations thereof. The display 3832 can interface to the processor(s) 38038, memory 3803, and fixed storage 3808, as well as other devices, such as input device(s) 3833, via the bus 3840. The display 3832 is linked to the bus 3840 via a video interface 3822, and transport of data between the display 3832 and the bus 3840 can be controlled via the graphics control 38238. In some embodiments, the display is a video projector. In some embodiments, the display is a head-mounted display (HMD) such as a VR headset. In further embodiments, suitable VR headsets include, by way of non-limiting examples, HTC Vive, Oculus Rift, Samsung Gear VR, Microsoft HoloLens, Razer OSVR, FOVE VR, Zeiss VR One, Avegant Glyph, Freefly VR headset, and the like. In still further embodiments, the display is a combination of devices such as those disclosed herein.

[0349] In addition to a display 3832, computer system 3800 may include one or more other peripheral output devices 3834 including, but not limited to, an audio speaker, a printer, aWSGR Attorney Docket No. 65297-702.601 storage device, and any combinations thereof. Such peripheral output devices may be connected to the bus 3840 via an output interface 3824. Examples of an output interface 3824 include, but are not limited to, a serial port, a parallel connection, a USB port, a FIREWIRE port, a THUNDERBOLT port, and any combinations thereof.

[0350] In addition or as an alternative, computer system 3800 may provide functionality as a result of logic hardwired or otherwise embodied in a circuit, which may operate in place of or together with software to execute one or more processes or one or more steps of one or more processes described or illustrated herein. Reference to software in this disclosure may encompass logic, and reference to logic may encompass software. Moreover, reference to a computer-readable medium may encompass a circuit (such as an IC) storing software for execution, a circuit embodying logic for execution, or both, where appropriate. The present disclosure encompasses any suitable combination of hardware, software, or both.

[0351] Those of skill in the art will appreciate that the various illustrative logical blocks, modules, circuits, and algorithm steps described in connection with the embodiments disclosed herein may be implemented as electronic hardware, computer software, or combinations of both. To clearly illustrate this interchangeability of hardware and software, various illustrative components, blocks, modules, circuits, and steps have been described above generally in terms of their functionality.

[0352] The various illustrative logical blocks, modules, and circuits described in connection with the embodiments disclosed herein may be implemented or performed with a general purpose processor, a digital signal processor (DSP), an application specific integrated circuit (ASIC), a field programmable gate array (FPGA) or other programmable logic device, discrete gate or transistor logic, discrete hardware components, or any combination thereof designed to perform the functions described herein. A general purpose processor may be a microprocessor, but in the alternative, the processor may be any conventional processor, controller, microcontroller, or state machine. A processor may also be implemented as a combination of computing devices, e.g., a combination of a DSP and a microprocessor, a plurality of microprocessors, one or more microprocessors in conjunction with a DSP core, or any other such configuration.

[0353] The steps of a method or algorithm described in connection with the embodiments disclosed herein may be embodied directly in hardware, in a software module executed by one or more processor(s), or in a combination of the two. A software module may reside in RAM memory, flash memory, ROM memory, EPROM memory, EEPROM memory, registers, hard disk, a removable disk, a CD-ROM, or any other form of storage mediumWSGR Attorney Docket No. 65297-702.601 known in the art. An exemplary storage medium is coupled to the processor such the processor can read information from, and write information to, the storage medium. In the alternative, the storage medium may be integral to the processor. The processor and the storage medium may reside in an ASIC. The ASIC may reside in a user terminal. In the alternative, the processor and the storage medium may reside as discrete components in a user terminal.

[0354] In accordance with the description herein, suitable computing devices include, by way of non-limiting examples, cloud computing platforms, distributed computing platforms, server clusters, server computers, desktop computers, laptop computers, notebook computers, sub-notebook computers, netbook computers, and netpad computers.

[0355] In some embodiments, the computing device includes an operating system configured to perform executable instructions. The operating system is, for example, software, including programs and data, which manages the device’s hardware and provides services for execution of applications. Those of skill in the art will recognize that suitable server operating systems include, by way of non-limiting examples, FreeBSD, OpenBSD, NetBSD®, Linux, Apple® Mac OS X Server®, Oracle® Solaris®, Windows Server®, and Novell® NetWare®. Those of skill in the art will recognize that suitable personal computer operating systems include, by way of non-limiting examples, Microsoft® Windows®, Apple® Mac OS X®, UNIX®, and UNIX-like operating systems such as GNU / Linux®. In some embodiments, the operating system is provided by cloud computing. Those of skill in the art will also recognize that suitable mobile smartphone operating systems include, by way of non-limiting examples, Nokia® Symbian® OS, Apple® iOS®, Research in Motion® BlackBerry OS®, Google® Android®, Microsoft® Windows Phone® OS, Microsoft® Windows Mobile® OS, Linux®, and Palm® WebOS®.

[0356] In some embodiments, the smart patch comprises a processor. The processor can be configured to run a command-based engine. The command-based engine can be a type of software architecture or control system that can be designed to execute discrete actions or operations in response to specific commands. The command-based engine can interpret instructions from a user, another program, or an automated process. The command-based engine can translate said instructions into actionable tasks. Each command can facilitate a distinct piece of functionality, such as, for example, performing a calculation, or updating a database. The command-based engine can manage the life cycle of said commands, including validation, scheduling, execution, error handling, or any combination thereof. Commandbased engines can employ patterns such as the Command Pattern, which can allowWSGR Attorney Docket No. 65297-702.601 commands to be treated as objects, which can enable queuing, logging, undo / redo functionality, dynamic execution, or any combination thereof. The command-based engine can be configured to control the one or more sensors of the smart patch. The command-based engine can be configured to manage connectivity with the Internet of Things or a local server. The Internet of Things can be a network of interconnected physical devices can be embedded with sensors, software, and / or other technologies to collect, exchange, and / or act on data over the internet.

[0357] In some embodiments, the processor is configured to run a rule engine. The rule engine can be a software system which can automate decision-making by applying a set of predefined rules to data or events. The rule engine can separate the decision logic from the underlying program, allowing rules, which can be expressed as conditional statements (e.g., “if this, then that”), to be created, modified, and / or managed independently. When data or events are input, the engine can evaluate the relevant rules, determine which conditions are satisfied, and execute the corresponding action. The evaluation, determination, and execution can occur in real time. In some embodiments, the rule engine is configured to monitor a multi-stage data ingestion pipeline. A multi-stage data ingestion pipeline can be a structured system which can be designed to collect, process, and / or transport data from multiple sources to a target storage or analytics environment in a series of organized stages. Unlike a simple, single-step ingestion process, a multi-stage pipeline can divide the workflow into steps (such as, for example, data extraction, validation, transformation, enrichment, and / or loading), which can allow each stage to perform specialized tasks. This can promote data quality, consistency, and reliability. Data can originate from diverse sources, such as, for example, databases, application programming interfaces, or Internet of Things devices, and the pipeline can manage the integration of these heterogeneous formats into a unified schema.Intermediate stages can include cleaning noisy or incomplete data, normalizing formats, aggregating metrics, or applying business rules before the final storage in a data warehouse, lake, or analytics system.

[0358] In some embodiments, the processor is configured to run a layered script engine. The layered script engine can be a software system which can execute scripts in a structured and / or hierarchical manner, where functionality can be organized across multiple layers of abstraction or responsibility. Each layer in the engine can be responsible for a specific aspect of script processing, such as, for example, parsing and / or syntax validation at the base layer, execution of core commands in the middle layer, and / or higher-level orchestration, context management, or integration with external systems at the top layer. This layered approach canWSGR Attorney Docket No. 65297-702.601 allow the engine to separate concerns, which can make it easier to maintain, extend, and debug scripts while providing modular control over execution flow. Scripts can interact with underlying resources, call predefined commands, or leverage higher-level application programming interfaces exposed by the engine, which can enable complex behaviors to be built from simpler components. In some embodiments, the layered script engine is configured to dynamically select protocol sequences based on a source of information comprising a gateway status or a power state. The gateway status can refer to the current operational condition or health of a device or software system that connects two different networks, which can serve as a bridge between local systems and external networks such as, for example, the internet or cloud services. Gateway status can include information about connectivity, performance, security, resource utilization, or any combination thereof, indicating whether the gateway is online, offline, or experiencing errors. It may also report metrics such as data throughput, packet loss, latency, and active connections, helping administrators monitor and manage network traffic effectively. In modern loT, industrial, or enterprise systems, gateway status is often continuously monitored and can trigger alerts or automated responses if thresholds are exceeded, or if anomalies are detected. The power state can refer to the current operational mode of an electronic device or system with respect to its energy consumption and / or functionality. The power state define whether the smart patch is fully active, partially active, or completely off, and can include intermediate modes such as, for example, sleep, hibernation, or idle, each of which can be designed to balance performance with energy efficiency. For example, in computers or mobile devices, the active state can allow full processing and responsiveness, while sleep mode can reduce power usage by shutting down nonessential components but retain memory contents and hibernate mode can save system state to storage before turning off almost entirely. Power states can manage energy consumption, extend battery life, and / or reduce thermal stress in portable systems. Additionally, modern hardware and operating systems can dynamically switch between power states based on workload, user activity, or environmental conditions, making power state management a factor for system performance and / or sustainability.

[0359] In some embodiments, the processor is configured to run an adaptive sensor fusion engine. The adaptive sensor fusion engine can refer to a software system which can combine and / or interpret data from one or more sensors to produce an accurate, reliable, and / or context-aware understanding of the environment or system it monitors. An adaptive engine can dynamically adjust how it weighs, filters, and / or correlates sensor inputs based on changing conditions, sensor reliability, or observed patterns. The adaptive nature of theWSGR Attorney Docket No. 65297-702.601 engine allows it to continuously learn and optimize fusion strategies, improving decisionmaking, detection accuracy, and / or system robustness. In some embodiments, the adaptive sensor fusion engine is configured to use time-aware, context-based logic to integrate sensor evaluation. The adaptive sensor fusion engine can orchestrate time-calibrated signal interpretation or rule-based multi-sensor interpretation. The adaptive sensor fusion engine can be robust against false positives. The false positive can occur when a sensor detects a stimulus, when in reality such a stimulus did not occur. That is, the system can accurately combine sensor data in a way that can minimize nonspecific signals that might otherwise be incorrectly interpreted as real events or conditions. The adaptive sensor fusion engine can facilitate robustness against false positives by cross-verifying data across multiple sensors; weighing sensor reliability dynamically, wherein sensors that are more accurate are given more weight or influence; and / or applying filtering and / or validation algorithms to help distinguish between real events and transient noise, glitches, or environmental interference.

[0360] In some embodiments, the processor is configured to run a time warp playback engine. The time warp playback engine can allow the user to manipulate the timing of a sequence without altering its intrinsic characteristics. The time warp playback engine can enable playback at variable speeds (e.g., slowing down, speeding up, or even reversing a sequence). The time warp playback engine can map the original timeline of the data to a new, warped timeline, using interpolation algorithms to fill in any gaps or adjust frames for smooth playback. The time warp playback engine can allow content to be stretched or compressed in time without introducing noticeable artifacts.

[0361] The processor can be configured to run a multi-stage data ingestion pipeline. The multi-stage data ingestion pipeline can be a structured system which can collect, process, and / or prepare data from multiple sources before it is stored or analyzed. The multi-stage data ingestion pipeline can divide the workflow into discrete stages, such as, for example, data extraction, validation, transformation, enrichment, loading, or any combination thereof. In the first stage, raw data can be collected from various sources including databases, application programming interfaces, sensors, or logs. The next stage(s) can include data cleaning and / or validation, which can help correct or flag missing or inconsistent data. Subsequent stages can involve transformation and / or enrichment, where data can be standardized, formatted, or combined with external datasets to make it more useful for analysis. Finally, the processed data can be loaded into a target system, such as a data warehouse, lake, or real-time analytics platform. The multi-stage data ingestion pipeline can correlate raw and derived sensor data with patient timelines.WSGR Attorney Docket No. 65297-702.601

[0362] In some embodiments, the processor can be configured to run a metadata-driven scenario replay. Metadata-driven scenario replay can refer to a process where the playback of recorded events is guided and controlled by metadata rather than just raw data. The metadata can act as an instructive layer that can dictate how scenarios are reconstructed and replayed. This can allow for flexible manipulation, such as, for example, adjusting timing, highlighting specific variables, filtering certain events, or exploring alternative outcomes, without modifying the original dataset. By separating the control logic from the underlying data, metadata-driven scenario replay can facilitate reproducible, customizable, and / or scalable testing or analysis. Metadata-driven scenario replay can promote reproducible quality assurance, demonstrations, and / or event verification.

[0363] In some embodiments, the processor can be configured to run accelerated time simulation. The accelerated time simulation can comprise validation of time-based rules. The time-based rules can comprise a missed, delayed, or skipped dose. Accelerated time simulation can refer to a technique to speed up the passage of time within a system or scenario so that long-term processes can be observed and / or analyzed in shorter real-world timeframe. Instead of waiting for events to unfold in real time, the simulation can compress or accelerate the timeline while maintaining the correct sequence, causality, and / or interactions of events.

[0364] In some embodiments, the processor can be configured to run event-state inspection tools. The event-state inspection tools can allow developers, testers, or analysts to observe, examine, and / or understand the relationship between events occurring in the system and the internal states those events produce or modify. The event-state inspection tools can inform what the system was doing at specific time points in time, capturing inputs, outputs, transitions, or state changes. The event-state inspection tools can facilitate the mapping of every system state change to an originating sensor event and / or a timestamp. The sensor event can be the opening of a package containing the smart patch, the removal of an adhesive liner on the smart patch, application of the smart patch applied, removal of the smart patch, or a dose administered or missed.

[0365] The processor can comprise a quality assurance platform that can facilitate the simulation, testing, and demonstration of the smart patch using a time manipulation interface to replay, fast-forward, pause, and inspect historical or hypothetical scenarios. The platform can input real or synthetic sensor data and can reproduce system behavior as if operating in real time. This can enable one or more of (1) validation of software logic, user interface transitions, and / or adherence states; (2) simulation of rare cases without needing patientWSGR Attorney Docket No. 65297-702.601 testing; (3) live demonstrations using historical data sets or accelerated time warps for investors or clinical stakeholders; and / or (4) regulatory-grade traceability of all system decisions based on past sensor inputs and timestamped rule evaluations. The quality assurance platform can facilitate switching between one or more modes. The modes can comprise testing, validation, and / or public demonstration modes. All modes can be driven by the same time engine.Non-transitory Computer Readable Storage Medium

[0366] In some embodiments, the platforms, systems, media, and methods disclosed herein include one or more non-transitory computer readable storage media encoded with a program including instructions executable by the operating system of an optionally networked computing device. In further embodiments, a computer readable storage medium is a tangible component of a computing device. In still further embodiments, a computer readable storage medium is optionally removable from a computing device. In some embodiments, a computer readable storage medium includes, by way of non-limiting examples, CD-ROMs, DVDs, flash memory devices, solid state memory, magnetic disk drives, magnetic tape drives, optical disk drives, distributed computing systems including cloud computing systems and services, and the like. In some cases, the program and instructions are permanently, substantially permanently, semi-permanently, or non-transitorily encoded on the media.Computer Programs

[0367] In some embodiments, the platforms, systems, media, and methods disclosed herein include at least one computer program, or use of the same. A computer program includes a sequence of instructions, executable by one or more processor(s) of the computing device’s CPU, written to perform a specified task. Computer readable instructions may be implemented as program modules, such as functions, objects, Application Programming Interfaces (APIs), computing data structures, and the like, which perform particular tasks or implement particular abstract data types. In light of the disclosure provided herein, those of skill in the art will recognize that a computer program may be written in various versions of various languages.

[0368] The functionality of the computer readable instructions may be combined or distributed as desired in various environments. In some embodiments, a computer program comprises one sequence of instructions. In some embodiments, a computer programWSGR Attorney Docket No. 65297-702.601 comprises a plurality of sequences of instructions. In some embodiments, a computer program is provided from one location. In other embodiments, a computer program is provided from a plurality of locations. In various embodiments, a computer program includes one or more software modules. In various embodiments, a computer program includes, in part or in whole, one or more web applications, one or more mobile applications, one or more standalone applications, one or more web browser plug-ins, extensions, add-ins, or add-ons, or combinations thereof.Software Modules

[0369] In some embodiments, the platforms, systems, media, and methods disclosed herein include software, server, and / or database modules, or use of the same. In view of the disclosure provided herein, software modules are created by techniques known to those of skill in the art using machines, software, and languages known to the art. The software modules disclosed herein are implemented in a multitude of ways. In various embodiments, a software module comprises a file, a section of code, a programming object, a programming structure, a distributed computing resource, a cloud computing resource, or combinations thereof. In further various embodiments, a software module comprises a plurality of files, a plurality of sections of code, a plurality of programming objects, a plurality of programming structures, a plurality of distributed computing resources, a plurality of cloud computing resources, or combinations thereof. In various embodiments, the one or more software modules comprise, by way of non-limiting examples, a web application, a mobile application, a standalone application, and a distributed or cloud computing application. In some embodiments, software modules are in one computer program or application. In other embodiments, software modules are in more than one computer program or application. In some embodiments, software modules are hosted on one machine. In other embodiments, software modules are hosted on more than one machine. In further embodiments, software modules are hosted on a distributed computing platform such as a cloud computing platform. In some embodiments, software modules are hosted on one or more machines in one location. In other embodiments, software modules are hosted on one or more machines in more than one location.Databases

[0370] In some embodiments, the platforms, systems, media, and methods disclosed hereinWSGR Attorney Docket No. 65297-702.601 include one or more databases, or use of the same. In view of the disclosure provided herein, those of skill in the art will recognize that many databases are suitable for storage and retrieval of information, for example customer incident data. In various embodiments, suitable databases include, by way of non-limiting examples, relational databases, nonrelational databases, object oriented databases, object databases, entity-relationship model databases, associative databases, XML databases, document oriented databases, and graph databases. Further non-limiting examples include SQL, PostgreSQL, MySQL, Oracle, DB2, Sybase, and MongoDB. In some embodiments, a database is Internet-based. In further embodiments, a database is web-based. In still further embodiments, a database is cloud computing-based. In a particular embodiment, a database is a distributed database. In other embodiments, a database is based on one or more local computer storage devices.Transdermal Drug Delivery Patch for Detecting Drug Dosages

[0371] In one embodiment, disclosed herein is a transdermal drug delivery smart patch. In some embodiments, the dosages can comprise dosages of drugs. In some embodiments, drugs can comprise drugs in a drug layer of the patch. The drug layer of the patch can comprise a drug-containing layer. The drug containing layer can comprise a cardiovascular drug, a central nervous system drug, an oncology drug, and autoimmune drug, or any combination thereof. The central nervous system drug can comprise a psychiatric drug. The psychiatric drug can comprise antipsychotics, antidepressants, anti-anxiety medications, anti-seizure medications, or any combination thereof. In some embodiments, the transdermal drug delivery smart patch can comprise a communication interface. In some embodiments, the communication interface can comprise a radio. In some embodiments, the communication interface can comprise a radio with an antenna. In some embodiments, the antenna can be a flex antenna. In some embodiments, the antenna can comprise a triple-band antenna. In some embodiments, the triple-band antenna can comprise a split-ring resonator, a half-ring resonator, or both. In some embodiments, the antenna can be fabricated from polymer material. In some embodiments, the antenna can comprise an ultra-wideband antenna. In some embodiments, the antenna can comprise a spiral-shaped antenna. In some embodiments, the spiral-shaped antenna can comprise a circularly polarized loop antenna. In some embodiments, the spiral-shaped antenna can comprise a flexible magnetic-based spiral antenna. In some embodiments, the antenna can have a conformal structure. In some embodiments, the antenna can comprise a multiple input multiple output (MIMO) antenna. In some embodiments, the antenna can be a dielectric-based meandering line antenna. In someWSGR Attorney Docket No. 65297-702.601 embodiments, the antenna can have a planar structure. In some embodiments, the antenna can be an ultra-thin antenna. In some embodiments, the antenna can be an ultra-miniaturized antenna. In some embodiments, the antenna can be a flexible loop antenna. In some embodiments, the antenna can be connected by wire to the processor, the sensors, or both. In some embodiments, the antenna can be wirelessly communicatively coupled to the processor, the sensors, or both.

[0372] In some embodiments, the transdermal drug delivery smart patch can further comprise one or more sensors. In some embodiments, the one or more sensors can comprise one or more of an ambient light sensor, a body temperature sensor, a capacitance sensor, a conductivity sensor, or any combination thereof. In some embodiments, the sensor can be configured to detect a status change of the smart patch. In some embodiments, the status change can comprise removing a packaging from the smart patch. In some embodiments, the packaging removed from the smart patch can be a backing material or liner. In some embodiments, the status change can further comprise removal of a liner from an adhesive layer of the smart patch. In some embodiments, the liner can comprise a single sided adhesive or a double sided adhesive. In some embodiments, the status change can further comprise applying the smart patch to the skin of the patient. In some embodiments, the status change can further comprise removing the smart patch from the skin of the patient. In some embodiments, the transdermal drug delivery patch can comprise a processor. In some embodiments, the processor can be communicatively coupled to the one or more sensors. In some embodiments, the processor can be communicatively coupled to the communication interface. In some embodiments, the processor can be communicatively coupled to the processor and the communication interface. In some embodiments, the processor can be configured to independently perform operations. In some embodiments, the processor does not receive any signals from an external source of signal. In some embodiments, the processor does not receive instructions from an external computing source, such as an external processor. In some embodiments, the processor is integrated into the chip only. In some embodiments, the processor is configured to automatically transit between a plurality of working conditions. In some embodiments, the processor is configured to automatically transit between a plurality of working conditions independently. In some embodiments, the processor is configured to automatically transit between a plurality of working conditions based on the status change of the smart patch. In some embodiments, the plurality of working conditions of the smart patch comprise a hibernation mode, a sleep mode, and a work mode. In some embodiments, the processor can be configured to detect one or more dosageWSGR Attorney Docket No. 65297-702.601 conditions. In some embodiments, dosage conditions can comprise information relating to an overdose of a drug, an underdose of a drug, a missed dosage of a drug, a delayed dosage of a drug, a missing dosage of a drug, a timing of a drug dosage, a change in drug dosage, or a combination thereof. In some embodiments, one or more dosage conditions can be detected based at least in part on the detected status change of the smart patch. In some embodiments, the one or more dosage conditions can be detected at least in part using a change in condition of the smart patch. In some embodiments, the processor can be configured to transmit smart patch status data. In some embodiments, the smart patch status data can comprise a change in status of the transdermal smart patch. In some embodiments, the smart patch status data can comprise a working condition of a smart patch. In some embodiments, the smart patch status data can comprise a hibernation mode, a work mode, and a sleep mode, or any combination thereof. In some embodiments, the processor can be configured to transmit one or more dosage conditions. In some embodiments, the processor can be configured to transmit one or more dosage conditions using the communication interface. In some embodiments, the one or more dosage conditions can comprise an overdose, an underdose, a missed dose, a

[0373] In some embodiments, the transdermal drug delivery smart patch further comprises a memory. In some embodiments, the memory is communicatively coupled to the processor. In some embodiments, the memory is configured to receive and store information from the processor relating to the patch status data of the transdermal drug delivery smart patch. In some embodiments, the one or more dosage conditions comprise an estimated dosage pattern relating to the patient. In some embodiments, the processor is further configured to generate the estimated dosage pattern based at least in part on a plurality of patch statuses stored in the memory. In some embodiments, the processor is further configured to generate an estimation of an overdose, an underdose, a missed dose, a mistimed dose, or any combination thereof relating to the patient based on the dosage pattern data. In some embodiments, the processor is further configured to output instructions to the communication interface to transmit a notification based at least in part on the estimation of the overdose, the underdose, the missed dose, the mistimed dose, or any combination thereof.

[0374] In some embodiments, the communication interface can be configured to transmit the notification over a network to an external processor or database. In some embodiments, the external process or database can comprise a remote server. In some embodiments, the remote server can be a cloud server. In some embodiments, the notification can comprise one or more of an alert notification relating to urgent care interventions, an alert notification relating to current drug dosage, a notification relating to drug dosage pattern data for the patient, aWSGR Attorney Docket No. 65297-702.601 notification relating to drug dosage pattern data for a plurality of patients, or any combination thereof. In some embodiments, the notification can be transmitted to an external processor or database. In some embodiments, the notification can be transmitted directly to a user. In some embodiments, the external processor or database can be configured to generate a dynamic notification message. In some embodiments, the notification can be an urgent notification. In some embodiments, the notification can be a non-urgent notification. In some embodiments, the notification can comprise one or more of a text message, an email, a push notification, a phone call, a page, or any combination thereof. In some embodiments, the dynamic notification message can be based at least in part on the notification transmitted by the drug delivery smart patch. In some embodiments, the external processor or database can comprise one or more artificial intelligence (Al) / machine learning (ML) models. In some embodiments, the AI / ML models can comprise Large Language Models (LLMs). In some embodiments, the LLMs can be configured to generate the dynamic notification message. In some embodiments, the dynamic notification message can comprise an LLM-generated personalized message. In some embodiments, the personalized message can comprise a personalized recipient. In some embodiments, the recipient of the personalized message can be modified based on one or more characteristics of the recipient. In some embodiments, the one or more characteristics of the recipient can comprise relationship with the patient, title of the recipient, user data of the recipient, or any combination thereof. In some embodiments, the notification can comprise a personalized generated message. In some embodiments, the personalized generated message can comprise one or more prompts. In some embodiments, the one or more prompts can be question prompts. In some embodiments, the one or more prompts can comprise query reminders relating to information about patient dosage. In some embodiments, the query reminders can be generated by LLMs in forms such as “Hi CareMinder, did mom take her medicine today? How is she doing this week?” In some embodiments, the processor can be further configured to receive signal connection data from the communication interface. In some embodiments, signal connection data comprises one or more of connection packets, connection robustness, minimal user requirements, minimal user burden, connection type, connection origin, connection security, connection protocols, or any combination thereof.

[0375] In some embodiments, the processor can be further configured to select a connection signal from the one or more signals. In some embodiments, the one or more signals can comprise short-range wireless signals near-field communication (NFC) signals, broadband, narrow band-internet of Things (NB-IoT), radio signals, WLAN, cellular signals, or anyWSGR Attorney Docket No. 65297-702.601 combination thereof. In some embodiments, the communication may take place in the signal range of about 2.4GHz to about 2.5GHz. In some embodiments, selecting the connection signal can be based at least in part on the signal connection data. In some embodiments, selecting the connection signal can be based at least in part on information relating to power level of the communication interface. In some embodiments, the information relating to the power level of the communication interface is based at least in part on the amount of energy remaining in the power source of the transdermal smart patch, amount of power consumed by the communication interface, or both, information relating to communication protocols, or any combination thereof. In some embodiments, the signal connection data can comprise one or more of signal strength, signal network type, signal host identity, security of signal connection, or any combination thereof. In some embodiments, the information relating to communication protocols comprises one or more of beacon protocols, advertising protocols, security protocols, authentication protocols, data privacy protocols, compliance protocols, or any combination thereof. In some embodiments, the processor can be further configured to output connection instructions to the communication interface. In some embodiments, the output connection instructions can comprise selecting a communication signal. In some embodiments, the output connection instructions can be based at least in part on the selected connection signal. In some embodiments, the communication interface can be further configured to connect to the selected connection signal of the one or more signals based on the instructions received from the processor. In some embodiments, the instructions can comprise an indication of which connection to select, a binary indication to select or not select the signal, or an instruction to leave a connection, or any combination thereof.

[0376] In another embodiment, disclosed herein is a transdermal drug delivery smart patch. In some embodiments, the transdermal drug delivery smart patch can comprise a drugcontaining layer. In some embodiments, the drug-containing layer can comprise a drug-inadhesive layer. In some embodiments, the adhesive can comprise a biologically compatible adhesive. In some embodiments, the transdermal drug delivery smart patch can comprise a backing layer. In some embodiments, the backing layer can comprise adhesive on a single side. In some embodiments, the transdermal drug delivery smart patch can comprise a liner. In some embodiments, the liner can be a release liner. In some embodiments, the transdermal drug delivery smart patch can comprise a power source. In some embodiments, the power source can comprise a battery. In some embodiments, the power source can be additively manufactured. In some embodiments, the power source can be printed. In some embodiments, the battery can comprise a printed battery. In some embodiments, the powerWSGR Attorney Docket No. 65297-702.601 source can be a lithium ion battery. In some embodiments, the power source can be a lithium / iodide battery. In some embodiments, the power source can comprise a lithium / iodine-polyvinylpyridine (PVP) system. In some embodiments, the power source can comprise a lithium / manganese dioxide battery. In some embodiments, the power source can comprise a lithium / carbon monofluoride battery. In some embodiments, the power source can comprise a lithium / carbon monofluoride and silver vanadium oxide battery. In some embodiments, the power source can comprise a lithium / silver vanadium oxide battery. In some embodiments, the power source can comprise a lithium / manganese dioxide battery. In some embodiments, the power source can comprise a hybrid cell battery. In some embodiments, the power source can comprise a rechargeable battery. In some embodiments, the power source can comprise a lithium polymer (LiPo) battery. In some embodiments, the power source can comprise multiple batteries. In some embodiments, the power source can comprise one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, twenty, or more than twenty batteries. In some embodiments, the power source can comprise stretchable batteries. In some embodiments, stretchable batteries can comprise magnesium and molybdenum bendable metal foils, polymers, or fibers, or any combination thereof. In some embodiments, the battery can be a printed battery. In some embodiments, the transdermal drug delivery smart patch can comprise an electronics layer. In some embodiments, the electronics layer can be configured to fit inside a window, notch, opening, drug layer cutout, or other hole in the drug layer. In some embodiments, the electronics layer can comprise an antenna. In some embodiments, the antenna can comprise a flex antenna. In some embodiments, the antenna can comprise a triple-band antenna. In some embodiments, the triple-band antenna can comprise a split-ring resonator, a half-ring resonator, or both. In some embodiments, the antenna can be fabricated from polymer material. In some embodiments, the antenna can comprise an ultra-wideband antenna. In some embodiments, the antenna can comprise a spiral-shaped antenna. In some embodiments, the spiral-shaped antenna can comprise a circularly polarized loop antenna. In some embodiments, the spiral-shaped antenna can comprise a flexible magnetic-based spiral antenna. In some embodiments, the antenna can have a conformal structure. In some embodiments, the antenna can comprise a multiple input multiple output (MEMO) antenna. In some embodiments, the antenna can be a dielectricbased meandering line antenna. In some embodiments, the antenna can have a planar structure. In some embodiments, the antenna can be an ultra-thin antenna. In some embodiments, the antenna can be an ultra-miniaturized antenna. In some embodiments, theWSGR Attorney Docket No. 65297-702.601 antenna can be a flexible loop antenna. In some embodiments, the antenna can be connected by wire to the processor, the sensors, or both. In some embodiments, the antenna can be wirelessly communicatively coupled to the processor, the sensors, or both.

[0377] In some embodiments, the electronics layer can comprise the power source. In some embodiments, the electronics layer can comprise a battery. In some embodiments, the electronics layer can comprise a printed battery. In some embodiments, the power source can be a lithium ion battery. In some embodiments, the power source can be a lithium / iodide battery. In some embodiments, the power source can comprise a lithium / iodine- polyvinylpyridine (PVP) system. In some embodiments, the power source can comprise a lithium / manganese dioxide battery. In some embodiments, the power source can comprise a lithium / carbon monofluoride battery. In some embodiments, the power source can comprise a lithium / carbon monofluoride and silver vanadium oxide battery. In some embodiments, the power source can comprise a lithium / silver vanadium oxide battery. In some embodiments, the power source can comprise a lithium / manganese dioxide battery. In some embodiments, the power source can comprise a hybrid cell battery. In some embodiments, the power source can comprise a rechargeable battery. In some embodiments, the power source can comprise a lithium polymer (LiPo) battery. In some embodiments, the power source can comprise multiple batteries. In some embodiments, the power source can comprise one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, twenty, or more than twenty batteries. In some embodiments, the power source can comprise stretchable batteries. In some embodiments, stretchable batteries can comprise magnesium and molybdenum bendable metal foils, polymers, or fibers, or any combination thereof. In some embodiments, the electronics layer can comprise a system on a chip.

[0378] In some embodiments, the electronics layer can comprise a flex circuit. In some embodiments, the flex circuit is a flexible circuit. In some embodiments, the flex circuit can comprise one or more sensors. In some embodiments, the flex circuit can comprise one or more flexible components. In some embodiments, the one or more flexible components can comprise a flexible antenna. The flexible antenna can comprise a printed antenna. In some embodiments, the one or more flexible components can comprise a flexible printed battery. In some embodiments, one or more sensors can be attached to the flex layer. In some embodiments, the system on a chip (SoC) can be attached to the flex layer. In some embodiments, the one or more sensors can be configured to detect environmental conditions around the transdermal drug delivery smart patch. In some embodiments, the environmentalWSGR Attorney Docket No. 65297-702.601 conditions can comprise environmental light, environmental temperature, environmental conductivity, or any combination thereof.

[0379] In some embodiments, the flex circuit is configured to support an external power supply. In some embodiments, the flex circuit comprises an internal battery. The flex circuit can comprise power switching circuitry to support an external power supply and an internal battery. The external power supply can facilitate testing. The internal battery can support standard operation. The flex circuit can comprise a biocompatible layer. The biocompatible layer can comprise a chemically inert material. The chemically inert material can comprise silicone, a fluoropolymer (e.g., polytetrafluoroethylene, fluorinated ethylene propylene, perfluoroalkoxy alkane), stainless steel, titanium, polyethylene, or any combination thereof. The chemically inert material can comprise Parylene and / or ceramic. Parylene (e.g., poly- para-xylylene) can be a polymer conformal coating. Parylene can provide a protective, uniform, and / or pinhole-free barrier. The Parylene can comprise Parylene C, Parylene N, or Parylene HT®. Parylene C can comprise a polymer of poly(monochloro-p-xylylene). Parylene N can comprise a polymer of poly(p-xylylene). Parylene HT® can comprise a polymer of poly(a,a,a',a'-tetrafluoro-p-xylylene). The ceramic can comprise aluminum oxide, silicon dioxide, titanium dioxide, or zirconium dioxide. The chemically inert material can comprise polydimethylsiloxane (PDMS), a silicone elastomer; chemically resistant fluorinated plastics; polyurethane (e.g., medical-grade thermoplastic polyurethane or polyurethane), a thermoplastic elastomer; a polyimide (e.g., DuPont Kapton®, medical-grade variants), a high- performance thermoset polymer; a silicone-urethane copolymer (e.g., PurSil™, CarboSil®), a hybrid medical polymer; a PEG-based hydrogel (Crosslinked PEGDA (e.g., Polyethylene glycol diacrylate), PEGMA (e.g., polyethylene glycol) monomethacrylate)); and / or a hydrophilic polymer network. The biocompatible layer can have a thickness of about 0.01- 100 pm. The thickness can be about 0.01 pm, 0.02 pm, 0.03 pm, 0.04 pm, 0.05 pm, 0.06 pm, 0.07 pm, 0.08 pm, 0.09 pm, 0.1 pm, 0.2 pm, 0.3 pm, 0.4 pm, 0.5 pm, 0.6 pm, 0.7 pm, 0.8 pm, 0.9 pm, 1 pm, 2, pm, 3 pm, 4 pm, 5 pm, 6 pm, 7 pm, 8 pm, 9 pm, 10 pm, 11 pm, 12 pm, 13 pm, 14 pm 15 pm, 16 pm, 17 pm, 18 pm, 19 pm, 20 pm, 21 pm, 22 pm, 23 pm, 24 pm, 25 pm, 26 pm, 27 pm, 28 pm, 29 pm, 30 pm, 31 pm, 32 pm, 33 pm, 34 pm, 35 pm, 36 pm, 37 pm, 38 pm, 39 pm, 40 pm, 41 pm, 42 pm, 43 pm, 44 pm, 45 pm, 46 pm, 47 pm, 48 pm, 49 pm, 50 pm, 51 pm, 52 pm, 53 pm, 54 pm, 55 pm, 56 pm, 57 pm, 58 pm, 59 pm,60 pm, 61 pm, 62 pm, 63 pm, 64 pm, 65 pm, 66 pm, 67 pm, 68 pm, 69 pm, 70 pm, 71 pm,72 pm, 73 pm, 74 pm, 75 pm, 76 pm, 77 pm, 78 pm, 79 pm, 80 pm, 81 pm, 82 pm, 83 pm,84 pm, 85 pm, 86 pm, 87 pm, 88 pm, 89 pm, 90 pm, 91 pm, 92 pm, 93 pm, 94 pm, 95 pm,WSGR Attorney Docket No. 65297-702.60196 pm, 97 pm, 98 pm, 99 pm, or 100 pm. The thickness can be 0.01-0.1 pm, 0.01-1 pm, 0.01-10 pm, 0.01-20 pm, 0.01-30 pm, 0.01-40 pm, 0.01-50 pm^.01-60 pm, 0.01-70 pm, 0.01-80 pm, 0.01-90 pm, 0.01-100 pm, 0.1-1 pm, 0.1-10 pm, 0.1-20 pm, 0.1-30 pm, 0.1-40 pm, 0.1-50 pm, 0.1-60 pm, 0.1-70 pm, 0.1-80 pm, 0.1-90 pm, 1-10 pm, 1-20 pm, 1-30 pm, 1-40 pm, 1-50 pm, 1-60 pm, 1-70 pm, 1-80 pm, 1-90 pm, 1-100 pm, 10-20 pm, 10-30 pm, 10-40 pm, 10-50 pm, 10-60 pm, 10-70 pm, 10-80 pm, 10-90 pm, 10-100 pm, 20-30 pm, 20- 40 pm, 20-50 pm, 20-60 pm, 20-70 pm, 20-80 pm, 20-90 pm, 20-100 pm, 30-40 pm, 30-50 pm, 30-60 pm, 30-70 pm, 30-80 pm, 30-90 pm, 30-100 pm, 40-50 pm, 40-60 pm, 40-70 pm, 40-80 pm, 40-90 pm, 40-100 pm, 50-60 pm, 50-70 pm, 50-80 pm, 50-90 pm, 50-100 pm, 60-70 pm, 60-80 pm, 60-90 pm, 60-100 pm, 70-80 pm, 70-90 pm, 70-100 pm, 80-90 pm, 80-100 pm, or 90-100 pm. The biocompatible layer can be configured to increase the shelf-life of the smart patch. The shelf-life can be extended by at least about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%,37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%,53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%,69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%,85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 100%,150%, 200%, 250%, 300%, 350%, 400%, 450%, 500%, or more relative to an equivalent smart patch not comprising the biocompatible layer. The shelf-life can be extended by at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or more months relative to an equivalent smart patch not comprising the biocompatible layer. The shelf-life can be extended by at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or more years relative to an equivalent smart patch not comprising the biocompatible layer. The shelf-life can be extended by at least about 1-12 months or 1-10 years relative to an equivalent smart patch not comprising the biocompatible layer. The biocompatible can be configured to shield the smart patch from Active Pharmaceutical Ingredient (API) vapors. The flex circuit can comprise one or more sectioned electronics. The sectioned electronics can facilitate a clear view of the internal structures of components of the flex circuit (e.g., printed circuit boards (PCBs), integrated circuits (ICs), and / or solder joints). The flex circuit can comprise one or more ground planes. A ground plane can be a large, conductive surface, e.g., a copper layer. The ground plane can provide a common reference point for electrical signals and a return path for current. The flex circuit can comprise a material which can be disposed of as nonhazardous waste. The flex circuit can be made of material with restricted / hazardousWSGR Attorney Docket No. 65297-702.601 substances at sufficiently low levels to be compliant with the EU’s Restriction of Hazardous Substances Directive (RoHS). The RoHS can be a directive which restricts (with exceptions) the use of ten hazardous substances in the manufacture of various types of electronic and electrical equipment. The RoHS-compliant material can comprise Lead (Pb), Mercury (Hg), Cadmium (Cd), Hexavalent Chromium (Cr VI), Polybrominated Biphenyls (PBB), P...

Claims

WSGR Attorney Docket No. 65297-702.601CLAIMSWHAT IS CLAIMED IS:

1. A transdermal drug delivery smart patch, comprising: a drug-containing layer; a communication interface; one or more sensors configured to detect a status change of the smart patch, the status change comprising one or more of (i) removing a packaging from the smart patch, (ii) removing a liner from an adhesive layer of the smart patch, (iii) applying the smart patch to the skin of the patient, and (iv) removing the smart patch from the skin of the patient; and a processor communicatively coupled to the one or more sensors and the communication interface, wherein the processor is configured to independently perform operations comprising:(a) automatically transiting between a plurality of working conditions based on the status change of the smart patch, wherein the plurality of working conditions of the smart patch comprises a hibernation mode, a sleep mode, and a work mode,(b) detecting one or more dosage conditions based at least in part on the detected status change of the smart patch; and(c) transmitting smart patch status data, or the one or more dosage conditions, or both, using the communication interface.

2. The transdermal drug delivery smart patch of claim 1, further comprising a memory.

3. The transdermal drug delivery smart patch of claim 2, wherein the memory is communicatively coupled to the processor.

4. The transdermal drug delivery smart patch of claim 2 or claim 3, wherein the memory is configured to receive and store information from the processor relating to the detected status change of the transdermal drug delivery smart patch.

5. The transdermal drug delivery smart patch of any one of claims 1-4, wherein the one or more dosage conditions comprise an estimated dosage pattern relating to the patient.WSGR Attorney Docket No. 65297-702.6016. The transdermal drug delivery smart patch of claim 5, wherein the processor is further configured to generate the estimated dosage pattern based at least in part on a plurality of detected status changes of the transdermal drug delivery smart patch stored in the memory.

7. The transdermal drug delivery smart patch of claim 5 or claim 6, wherein the processor is further configured to generate an estimation of an overdose, an underdose, a missed dose, a mistimed dose, or any combination thereof relating to the patient based on the dosage pattern data.

8. The transdermal drug delivery smart patch of claim 7, wherein the processor is further configured to output instructions to the communication interface to transmit a notification based at least in part on the estimation of the overdose, the underdose, the missed dose, the mistimed dose, or any combination thereof.

9. The transdermal drug delivery smart patch of claim 8, wherein the communication interface is configured to transmit the notification over a network to an external processor or database.

10. The transdermal drug delivery smart patch of claim 8 or claim 9, wherein the notification comprises one or more of an alert notification relating to urgent care interventions, an alert notification relating to current drug dosage, a notification relating to drug dosage pattern data for the patient, a notification relating to drug dosage pattern data for a plurality of patients, or any combination thereof.

11. The transdermal drug delivery smart patch of claim 9 or claim 10, wherein the external processor or database generates a dynamic notification message based at least in part on the notification transmitted by the drug delivery smart patch.

12. The transdermal drug delivery smart patch of any one of claims 9-11, wherein the external processor or database comprises one or more artificial intelligence (Al) / machine learning (ML) models, for example Large Language Models (LLMs) configured to generate the dynamic notification message.

13. The transdermal drug delivery smart patch of any one of claims 1-12, wherein the processor is further configured to receive signal connection data from the communication interface.WSGR Attorney Docket No. 65297-702.60114. The transdermal drug delivery smart patch of claim 13, wherein the processor is further configured to select a connection signal from the one or more signals based at least in part on the signal connection data, information relating to power level of the communication interface, information relating to communication protocols, or any combination thereof.

15. The transdermal drug delivery smart patch of claim 13 or claim 14, wherein the signal connection data comprises one or more of signal strength, signal network type, signal host identity, security of signal connection, or any combination thereof.

16. The transdermal drug delivery smart patch of claim 14 or claim 15, wherein the information relating to communication protocols comprises one or more of beacon protocols, advertising protocols, security protocols, authentication protocols, data privacy protocols, compliance protocols, or any combination thereof.

17. The transdermal drug delivery smart patch of any one of claims 14-16, wherein the processor is further configured to output connection instructions to the communication interface based at least in part on the selected connection signal.

18. The transdermal drug delivery smart patch of claim 17, wherein the communication interface is further configured to connect to the selected connection signal of the one or more signals based on the instructions received from the processor.

19. A transdermal drug delivery smart patch, comprising: a drug-containing layer, wherein the drug-containing layer comprises a drug-inadhesive layer; a backing layer; a liner; a power source; an electronics layer, wherein the electronics layer comprises a flex circuit, wherein the flex circuit comprises:WSGR Attorney Docket No. 65297-702.601(a) one or more sensors configured to detect environmental conditions around the transdermal drug delivery smart patch,(b) a communication interface,(c) a processor communicatively coupled to the one or more sensors and the communication interface, wherein the processor is configured to independently perform operations comprising:(i) detecting a status change of the patch based at least in part on the detected environmental conditions;(ii) generating predictions relating to dosing information based at least in part on the detected status change of the patch; and(iii) transmitting smart patch status data using the communication interface.

20. The transdermal drug delivery smart patch of claim 19, wherein the flex layer is sealed from the environment.

21. The transdermal drug delivery smart patch of claim 19 or claim 20, wherein the flex layer is sealed using a non-permeable coating.

22. The transdermal drug delivery smart patch of any one of claims 19-21, wherein one or more of the power source, the one or more sensors, the communication interface, or the processor, or any combination thereof, are additively manufactured.

23. The transdermal drug delivery smart patch of any one of claims 19-22, wherein the one or more sensors comprise one or more of light sensors, body temperature sensors, capacitance sensors, resistance sensors, or any combination thereof.

24. The transdermal drug delivery smart patch of any one of claims 19-23, wherein the processor is configured to receive data from the one or more sensors simultaneously.WSGR Attorney Docket No. 65297-702.60125. The transdermal drug delivery smart patch of any one of claims 19-24, wherein the drug-in-adhesive layer comprises an opening configured to receive at least a portion of the electronics layer.

26. The transdermal drug delivery smart patch of claim 25, wherein the drug-in adhesive layer opening is further configured to receive the flex circuit, the one or more sensors, or both.

27. A transdermal drug delivery smart patch, comprising: one or more layers, the one or more layers comprising a drug and an adhesive; a communication interface; one or more sensors configured to detect a status change of the smart patch, the status change comprising one or more of (i) removing a packaging from the smart patch, (ii) removing a liner from the smart patch, (iii) applying the smart patch to the skin of a patient, and (iv) removing the smart patch from the skin of the patient; and a processor communicatively coupled to the one or more sensors and the communication interface, wherein the processor is configured to independently perform operations comprising:(a) transiting between a plurality of working conditions based on the status change of the smart patch, wherein the plurality of working conditions of the smart patch comprises a hibernation mode, a sleep mode, and a work mode,(b) automatically and periodically transiting between the sleep mode and the work mode, and(c) transmitting smart patch status data, using the communication interface.

28. The transdermal drug delivery smart patch of claim 27, further comprising a memory.

29. The transdermal drug delivery smart patch of claim 28, wherein the memory is communicatively coupled to the processor.WSGR Attorney Docket No. 65297-702.60130. The transdermal drug delivery smart patch of any one of claims 27-29, wherein the memory is configured to receive and store information from the processor relating to the patch status data of the transdermal drug delivery smart patch.

31. The transdermal drug delivery smart patch of any one of the preceding claims, further comprising a flex circuit, wherein the flex circuit comprises the processor.

32. The transdermal drug delivery smart patch of claim 31, wherein the flex circuit further comprises the memory.

33. The transdermal drug delivery smart patch of claim 31 or claim 32, wherein the flex circuit further comprises the communication interface.

34. The transdermal drug delivery smart patch of any one of the preceding claims, wherein the communication interface is a flex antenna.

35. The transdermal drug delivery smart patch of claim 34, wherein the flex antenna is communicatively coupled to the flex circuit.

36. The transdermal drug delivery smart patch of any one of claims 27-34, wherein the communication interface is configured to transmit status information over a network to an external processor or database, wherein the status information comprises a current status of the smart patch, a prior status of the smart patch, or a combination thereof.

37. The transdermal drug delivery smart patch of any one of the preceding claims, further comprising a power source (e.g., printed battery).

38. The transdermal drug delivery smart patch of claim 37, wherein the power source (e.g., printed battery) is coupled to the flex circuit.

39. The transdermal drug delivery smart patch of any one of the preceding claims, further comprising a flex circuit, wherein the flex circuit comprises a system-on-a-chip and a flex layer.

40. The transdermal drug delivery smart patch of any one of the preceding claims, further comprising a flex circuit, wherein the flex circuit is coated with a non-permeable coating (e.g., epoxy).WSGR Attorney Docket No. 65297-702.60141. The transdermal drug delivery smart patch of any one of the preceding claims, further comprising a flex antenna, wherein the flex antenna is coated with a non-permeable coating (e.g., epoxy).

42. The transdermal drug delivery smart patch of any one of the preceding claims, wherein the power source is coated with a non-permeable coating (e.g., epoxy).

43. The transdermal drug delivery smart patch of any one of claims 27-42, wherein the one or more layers comprises a first layer comprising the drug.

44. The transdermal drug delivery smart patch of claim 43, wherein the first layer comprises the adhesive.

45. The transdermal drug delivery smart patch of claim 43 or claim 44, wherein removing the liner from the smart patch comprises removing the liner from the first layer.

46. The transdermal drug delivery smart patch of any one of claims 43-45, further comprising a release liner, wherein the release liner is configured adjacent to the first layer.

47. The transdermal drug delivery smart patch of any one of claims 27-46, wherein the one or more layers further comprises a second layer, wherein the second layer comprises the adhesive.

48. The transdermal drug delivery smart patch of claim 47, wherein removing the liner from the smart patch comprises removing the liner from the second layer.

49. The transdermal drug delivery smart patch of either of claims 47 or 48, further comprising a release liner, wherein the release liner is configured adjacent to the second layer.

50. The transdermal drug delivery smart patch of any one of claims 27-49, wherein the one or more layers comprise an electronic layer, the electronic layer comprising the flex antenna, the flex circuit, the power source (e.g., printed battery), or a combination thereof.

51. The transdermal drug delivery smart patch of any one of claims 27-50, wherein the one or more layers comprise an electronic layer, the electronic layer comprising the flex antenna, the flex circuit, and the power source (e.g., printed battery).WSGR Attorney Docket No. 65297-702.60152. The transdermal drug delivery smart patch of any one of claims 27-51, wherein the first layer is affixed to the electronic layer, or the coating thereof.

53. The transdermal drug delivery smart patch of claim 52, wherein the first layer is affixed to the electronic layer, or the coating thereof, with a double sided adhesive.

54. The transdermal drug delivery smart patch of any one of claims 27-53, wherein the one or more layers comprises a backing layer, wherein the backing layer comprises an adhesive side and a non-adhesive side, and the adhesive side of the backing layer is affixed to the electronic layer, or the coating thereof.

55. The transdermal drug delivery smart patch of any one of claims 27-54, wherein the first layer comprises a cutout, and wherein at least a portion of the electronic layer is configured within the cutout of the first layer.

56. The transdermal drug delivery smart patch of any one of claims 27-55, wherein the second layer comprises a cut out, and wherein at least a portion of the electronic layer is configured within the cut out of the second layer.

57. The transdermal drug delivery smart patch of any one of the preceding claims, wherein the one or more sensors comprise a light sensor, a temperature sensor, a capacitance sensor, or a combination thereof.

58. The transdermal drug delivery smart patch of any one of the preceding claims, wherein the one or more sensors comprise a light sensor, a temperature sensor, and a capacitance sensor.

59. The transdermal drug delivery smart patch of any one of claims 19-58, wherein the electronic layer comprises a non-permeable coating (e.g., epoxy).

60. The transdermal drug delivery smart patch of any one of the preceding claims, wherein the processor is configured to independently perform operations comprising adjusting antenna transmission power levels (e.g., automatically and / or periodically).WSGR Attorney Docket No. 65297-702.60161. The transdermal drug delivery smart patch of any one of the preceding claims, wherein the processor is configured to independently perform operations comprising automatically determining a preferred cloud connection.

62. The transdermal drug delivery smart patch of any one of the preceding claims, wherein the processor is configured to independently perform operations comprising automatically determining antenna transmission power level and communication protocol based on a prioritized list of options.

63. The transdermal drug delivery smart patch of any one of the preceding claims, wherein the processor is configured to independently perform operations comprising authenticating cloud based connections.

64. The transdermal drug delivery smart patch of any one of the preceding claims, wherein the processor is configured to independently perform operations comprising encrypting data.

65. The transdermal drug delivery smart patch of any one of the preceding claims, wherein the processor is configured to independently perform operations comprising storing only anonymous (no patient identifiable) data.

66. The transdermal drug delivery smart patch of any one of the preceding claims, wherein the processor is configured to independently perform operations comprising determining patient adherence to dosing protocols.

67. The transdermal drug delivery smart patch of any one of the preceding claims, wherein the drug is a GLP-1 agonist.

68. The transdermal drug delivery smart patch of any one of claims 19-26 or 31-67, wherein the flex circuit is configured to support an external power supply.

69. The transdermal drug delivery smart patch of any one of claims 19-26 or 31-68, wherein the flex circuit comprises an internal battery.

70. The transdermal drug delivery smart patch of any one of claims 19-26 or 31-69, wherein the flex circuit comprises a biocompatible layer.WSGR Attorney Docket No. 65297-702.60171. The transdermal drug delivery smart patch of claim 70, wherein the biocompatible layer comprises a chemically inert material.

72. The transdermal drug delivery smart patch of any one of claim 71, wherein the chemically inert material comprises a parylene, ceramic, aluminum oxide, silicon dioxide, titanium dioxide, zirconium dioxide, or any combination thereof.

73. The transdermal drug delivery smart patch of any one of claims 19-26 or 31-72, wherein the flex circuit comprises one or more sectioned electronics.

74. The transdermal drug delivery smart patch of any one of claims 19-26 or 31-73, wherein the flex circuit comprises one or more ground planes.

75. The transdermal drug delivery smart patch of any one of claims 71-74, wherein the biocompatible layer has a thickness of about 0.01-100 pm.

76. The transdermal drug delivery patch of claim 75, wherein the biocompatible layer has a thickness of about 0.01-80 pm.

77. The transdermal drug delivery patch of claim 75 or claim 76, wherein the biocompatible layer has a thickness of about 0.01-60 pm.

78. The transdermal drug delivery patch of any one of claims 75-77, wherein the biocompatible layer has a thickness of about 0.01-40 pm.

79. The transdermal drug delivery patch of any one of claims 75-78, wherein the biocompatible layer has a thickness of about 0.01-20 pm.

80. The transdermal drug delivery patch of any one of claims 75-79, wherein the biocompatible layer has a thickness of about 0.01-10 pm.

81. The transdermal drug delivery patch of any one of claims 75-80, wherein the biocompatible layer has a thickness of about 0.01-1 pm.

82. The transdermal drug delivery smart patch of any one of claims 71-81, wherein the biocompatible layer is configured to increase the shelf-life of the smart patch.WSGR Attorney Docket No. 65297-702.60183. The transdermal drug delivery smart patch of claim 82, wherein the biocompatible layer is configured to increase the shelf-life of the smart patch by 1-12 months.

84. The transdermal drug delivery smart patch of claim 82 or claim 83, wherein the biocompatible layer is configured to increase the shelf-life of the smart patch by 1-10 years.

85. The transdermal drug delivery smart patch of any one of claims 71-84, wherein the biocompatible layer is configured to shield the smart patch from active pharmaceutical ingredient (API) vapors.

86. The transdermal drug delivery smart patch of any one of claims 19-26 or 31-85, wherein the flex circuit is made of a material comprising one or more substances present at sufficiently low levels to be compliant with the Restriction of Hazardous Substances Directive (RoHS).

87. The transdermal drug delivery patch of claim 86, wherein the one or more substances comprises Lead (Pb), Mercury (Hg), Cadmium (Cd), Hexavalent Chromium (Cr VI), Polybrominated Biphenyls (PBB), Polybrominated Diphenyl Ethers (PBDE), Bis(2- ethylhexyl) phthalate (DEHP), Benzyl butyl phthalate (BBP), Dibutyl phthalate (DBP), Diisobutyl phthalate (DIBP) or any combination thereof.

88. A system comprising:(a) the transdermal drug delivery smart patch of any one of the preceding claims; and(b) an electronic display comprising a user interface.

89. The system of claim 88, wherein the processor is configured to run a command-based engine.

90. The system of claim 89, wherein the command-based engine is configured to control the one or more sensors.

91. The system of claim 89 or claim 90, wherein the command-based engine is configured to manage connectivity with the Internet of Things or a local server.WSGR Attorney Docket No. 65297-702.60192. The system of any one of claims 88-91, wherein the processor is configured to run a rule engine.

93. The system of claim 92, wherein the rule engine is configured to monitor a multistage data ingestion pipeline.

94. The system of any one of claims 88-93, wherein the processor is configured to run a layered script engine.

95. The system of claim 94, wherein the layered script engine is configured to dynamically select protocol sequences based on a source of information comprising a gateway status or a power state.

96. The system of any one of claims 88-95, wherein the processor is configured to run an adaptive sensor fusion engine.

97. The system of claim 96, wherein the adaptive sensor fusion engine is configured to use time-aware, context-based logic to integrate sensor evaluation.

98. The system of any one of claims 88-97, wherein the user interface is configured to output the smart patch status data.

99. The system of claim 98, wherein the user interface is configured to output the smart patch status data in a format comprising a medication regimen.

100. The system of claim 98 or claim 99, wherein the user interface is configured to output the smart patch status data in a format comprising a smart patch replacement schedule.

101. The system of any one of claims 98-100, wherein the user interface is configured to output the smart patch status data in a format comprising an adherence record.

102. The system of any one of claims 98-101, wherein the user interface is configured to output the smart patch status data in a format comprising a visual or auditory alert of an upcoming dose, an overdose, an underdose, a missed dose, a mistimed dose, or any combination thereof.WSGR Attorney Docket No. 65297-702.601103. The system of any one of claims 88-102, wherein the user interface is configured to display three to seven temporal phases of drug dosing.

104. The system of claim 103, wherein the user interface is configured to display three temporal phases of drug dosing.

105. The system of claim 103, wherein the user interface is configured to display four temporal phases of drug dosing.

106. The system of claim 103, wherein the user interface is configured to display five temporal phases of drug dosing.

107. The system of claim 103, wherein the user interface is configured to display six temporal phases of drug dosing.

108. The system of claim 103, wherein the user interface is configured to display seven temporal phases of drug dosing.

109. The system of claim 103, wherein the three to seven temporal phases are categorized by color.

110. The system of any one of claims 88-109, wherein the user interface is configured to display a list of one or more medicines to be taken during a specific time window.

111. The system of claim 110, wherein the user interface is configured to display a brand name or a generic name of the one or more medicines.

112. The system of claim 110 or claim 111, wherein the list of one or more medicines is categorized by medical condition.

113. A method for transdermal drug delivery and monitoring in a patient in need thereof comprising:(a) providing a transdermal drug delivery smart patch, comprising:(i) a drug-containing layer, wherein the drug-containing layer comprises a drug-in-adhesive layer;WSGR Attorney Docket No. 65297-702.601(ii) a backing layer;(iii) a liner;(iv) a power source; and(v) an electronics layer, wherein the electronics layer comprises a flex circuit, wherein the flex circuit comprises: a. one or more sensors configured to detect environmental conditions around the transdermal drug delivery smart patch; and b. a communication interface; and(b) detecting a status change of the smart patch based at least in part on the detected environmental conditions;(c) detecting one or more dosage conditions based at least in part on the detected status change of the smart patch;(d) transmitting the smart patch status data from the one or more sensors to a processor communicatively coupled to the one or more sensors using the communication interface; and(e) outputting the smart patch status data using an electronic display comprising a user interface, wherein the user interface is configured to display a medication regimen, a smart patch replacement schedule, or an adherence record.

114. The method of claim 113, wherein the flex layer is sealed from the environment.

115. The method of claim 113 or claim 114, wherein the flex layer is sealed using a non- permeable coating.

116. The method of any one of claims 113-115, wherein one or more of the power source, the one or more sensors, the communication interface, or the processor, or any combination thereof, are additively manufactured.WSGR Attorney Docket No. 65297-702.601117. The method of any one of claims 113-116, wherein the one or more sensors comprise one or more of light sensors, body temperature sensors, capacitance sensors, resistance sensors, or any combination thereof.

118. The method of any one of claims 113-117, wherein the processor is configured to receive data from the one or more sensors simultaneously.

119. The method of any one of claims 113-118, wherein the drug-in-adhesive layer comprises an opening configured to receive at least a portion of the electronics layer.

120. The method of claim 119, wherein the drug-in adhesive layer opening is further configured to receive the flex circuit, the one or more sensors, or both.

121. A method for transdermal drug delivery and monitoring in a patient in need thereof comprising:(a) providing a transdermal drug delivery smart patch, comprising:(i) a drug-containing layer;(ii) a communication interface; and(iii) one or more sensors configured to detect a status change of the smart patch, the status change comprising one or more of: a. removing a packaging from the smart patch; b. removing a liner from an adhesive layer of the smart patch; c. applying the smart patch to the skin of the patient; and d. removing the smart patch from the skin of the patient; and(iv) a processor communicatively coupled to the one or more sensors and the communication interface;(b) detecting the status change of the smart patch;(c) detecting one or more dosage conditions based at least in part on the detected status change of the smart patch;WSGR Attorney Docket No. 65297-702.601(d) transmitting smart patch status data, or the one or more dosage conditions, or both, to the processor using the communication interface; and(e) outputting the information using an electronic display comprising a user interface, wherein the user interface is configured to display a medication regimen, a smart patch replacement schedule, or an adherence record.

122. The method of any one of claims 113-121, wherein the smart patch further comprises a memory.

123. The method of claim 122, wherein the memory is communicatively coupled to the processor.

124. The method of claim 122 or claim 123, wherein the memory is configured to receive and store information from the processor relating to the detected status change of the smart patch.

125. The method of any one of claims 113-124, wherein the one or more dosage conditions comprise an estimated dosage pattern relating to the patient.

126. The method of claim 125, wherein the processor is further configured to generate the estimated dosage pattern based at least in part on a plurality of detected status changes of the transdermal drug delivery smart patch stored in the memory.

127. The method of claim 125 or claim 126, wherein the processor is further configured to generate an estimation of an overdose, an underdose, a missed dose, a mistimed dose, or any combination thereof relating to the patient based on the dosage pattern data.

128. The method of claim 127, wherein the processor is further configured to output instructions to the communication interface to transmit a notification based at least in part on the estimation of the overdose, the underdose, the missed dose, the mistimed dose, or any combination thereof.

129. The method of claim 128, wherein the communication interface is configured to transmit the notification over a network to an external processor or database.

130. The method of claim 128 or claim 129, wherein the notification comprises one or more of an alert notification relating to urgent care interventions, an alert notification relating to current drug dosage, a notification relating to drug dosage pattern data for the patient, aWSGR Attorney Docket No. 65297-702.601 notification relating to drug dosage pattern data for a plurality of patients, or any combination thereof.

131. The method of claim 129 or claim 130, wherein the external processor or database generates a dynamic notification message based at least in part on the notification transmitted by the drug delivery smart patch.

132. The method of any one of claims 129-131, wherein the external processor or database comprises one or more artificial intelligence (Al) / machine learning (ML) models, for example Large Language Models (LLMs) configured to generate the dynamic notification message.

133. The method of any one of claims 113-132, wherein the processor is further configured to receive signal connection data from the communication interface.

134. The method of claim 133, wherein the processor is further configured to select a connection signal from the one or more signals based at least in part on the signal connection data, information relating to power level of the communication interface, information relating to communication protocols, or any combination thereof.

135. The method of claim 133 or claim 134, wherein the signal connection data comprises one or more of signal strength, signal network type, signal host identity, security of signal connection, or any combination thereof.

136. The method of claim 134 or claim 135, wherein the information relating to communication protocols comprises one or more of beacon protocols, advertising protocols, security protocols, authentication protocols, data privacy protocols, compliance protocols, or any combination thereof.

137. The method of any one of claims 134-136, wherein the processor is further configured to output connection instructions to the communication interface based at least in part on the selected connection signal.

138. The method of claim 137, wherein the communication interface is further configured to connect to the selected connection signal of the one or more signals based on the instructions received from the processor.

139. The method of any one of claims 121-138, wherein the smart patch further comprises a flex circuit, and wherein the flex circuit comprises the processor.WSGR Attorney Docket No. 65297-702.601140. The method of claim 139, wherein the flex circuit further comprises the memory.

141. The method of claim 139 or claim 140, wherein the flex circuit further comprises the communication interface.

142. The method of any one of claims 139-141, wherein the communication interface is a flex antenna.

143. The method of claim 142, wherein the flex antenna is communicatively coupled to the flex circuit.

144. The method of any one of claims 113-143, wherein the communication interface is configured to transmit status information over a network to an external processor or database, wherein the status information comprises a current status of the smart patch, a prior status of the smart patch, or a combination thereof.

145. The method of any one of claims 121-144, wherein the smart patch further comprises a power source (e.g., printed battery).

146. The method of any one of claims 113-120 or 145, wherein the power source (e.g., printed battery) is coupled to the flex circuit.

147. The method of any one of claims 113-120 or 139-146, wherein the flex circuit comprises a system-on-a-chip and a flex layer.

148. The method of any one of claims 113-120 or 139-147, wherein the flex circuit is coated with a non-permeable coating (e.g., epoxy).

149. The method of any one of claims 142-148, wherein the flex antenna is coated with a non-permeable coating (e.g., epoxy).

150. The method of any one of claims 113-120 or 145-149, wherein the power source is coated with a non-permeable coating (e.g., epoxy).

151. The method of any one of claims 113-150, wherein the smart patch comprises one or more layers, wherein the one or more layers comprise a first layer comprising the drug.WSGR Attorney Docket No. 65297-702.601152. The method of claim 151, wherein the first layer comprises an adhesive.

153. The method of claim 151 or claim 152, wherein removing the liner from the smart patch comprises removing the liner from the first layer.

154. The method of any one of claims 113-153, wherein the smart patch further comprises a release liner.

155. The method of claim 154, wherein the release liner is configured adjacent to the first layer.

156. The method of any one of claims 151-155, wherein the one or more layers further comprises a second layer.

157. The method of claim 156, wherein the second layer comprises the adhesive.

158. The method of claim 156 or claim 157, wherein removing the liner from the smart patch comprises removing the liner from the second layer.

159. The method of any one of claims 156-158, wherein the release liner is configured adjacent to the second layer.

160. The method of any one of claims 151-159, wherein the one or more layers comprise an electronic layer, the electronic layer comprising the flex antenna, the flex circuit, the power source (e.g., printed battery), or a combination thereof.

161. The method of any one of claims 151-160, wherein the one or more layers comprise an electronic layer, the electronic layer comprising the flex antenna, the flex circuit, and the power source (e.g., printed battery).

162. The method of claim 160 or claim 161, wherein the first layer is affixed to the electronic layer, or the coating thereof.

163. The method of any one of claims 160-162, wherein the first layer is affixed to the electronic layer, or the coating thereof, with a double sided adhesive.WSGR Attorney Docket No. 65297-702.601164. The method of any one of claims 151-163, wherein the one or more layers comprises a backing layer, wherein the backing layer comprises an adhesive side and a non-adhesive side, and the adhesive side of the backing layer is affixed to the electronic layer, or the coating thereof.

165. The method of any one of claims 160-164, wherein the first layer comprises a cutout, and wherein at least a portion of the electronic layer is configured within the cutout of the first layer.

166. The method of any one of claims 160-165, wherein the second layer comprises a cut out, and wherein at least a portion of the electronic layer is configured within the cut out of the second layer.

167. The method of any one of claims 113-166, wherein the one or more sensors comprise a light sensor, a temperature sensor, a capacitance sensor, or a combination thereof.

168. The method of any one of claims 113-167, wherein the one or more sensors comprise a light sensor, a temperature sensor, and a capacitance sensor.

169. The method of any one of claims 160-168, wherein the electronic layer comprises a non-permeable coating (e.g., epoxy).

170. The method of any one of claims 113-169, wherein the processor is configured to independently perform operations comprising adjusting antenna transmission power levels (e.g., automatically and / or periodically).

171. The method of any one of claims 113-170, wherein the processor is configured to independently perform operations comprising automatically determining a preferred cloud connection.

172. The method of any one of claims 113-171, wherein the processor is configured to independently perform operations comprising automatically determining antenna transmission power level and communication protocol based on a prioritized list of options.

173. The method of any one of claims 113-172, wherein the processor is configured to independently perform operations comprising authenticating cloud based connections.WSGR Attorney Docket No. 65297-702.601174. The method of any one of claims 133-173, wherein the processor is configured to independently perform operations comprising encrypting data.

175. The method of any one of claims 113-174, wherein the processor is configured to independently perform operations comprising storing only anonymous (no patient identifiable) data.

176. The method of any one of claims 113-175, wherein the processor is configured to independently perform operations comprising determining patient adherence to dosing protocols.

177. The method of any one of claims 113-176, wherein the drug is a GLP-1 agonist.

178. The method of any one of claims 113-120 or 139-177, wherein the flex circuit is configured to support an external power supply.

179. The method of any one of claims 113-120 or 139-178, wherein the flex circuit comprises an internal battery.

180. The method of any one of claims 113-120 or 139-179, wherein the flex circuit comprises a biocompatible layer.

181. The method of claim 180, wherein the biocompatible layer comprises a chemically inert material.

182. The method of claim 181, wherein the material comprises a parylene, ceramic, aluminum oxide, silicon dioxide, titanium dioxide, zirconium dioxide, or any combination thereof.

183. The method of any one of claims 113-120 or 139-182, wherein the flex circuit comprises one or more sectioned electronics.

184. The method of any one of claims 113-120 or 139-183, wherein the flex circuit comprises one or more ground planes.

185. The method of any one of claims 180-184, wherein the biocompatible layer has a thickness of about 0.01-100 pm.WSGR Attorney Docket No. 65297-702.601186. The method of any one of claims 180-185, wherein the biocompatible layer has a thickness of about 0.01-80 pm.

187. The method of any one of claims 180-186, wherein the biocompatible layer has a thickness of about 0.01-60 pm.

188. The method of any one of claims 180-187, wherein the biocompatible layer has a thickness of about 0.01-40 pm.

189. The method of any one of claims 180-188, wherein the biocompatible layer has a thickness of about 0.01-20 pm.

190. The method of any one of claims 180-189, wherein the biocompatible layer has a thickness of about 0.01-10 pm.

191. The method of any one of claims 180-190, wherein the biocompatible layer has a thickness of about 0.01-1 pm.

192. The method of any one of claims 180-191, wherein the biocompatible layer is configured to increase the shelf-life of the smart patch.

193. The method of claim 192, wherein the biocompatible layer is configured to increase the shelf-life of the smart patch by 1-12 months.

194. The method of claim 192, wherein the biocompatible layer is configured to increase the shelf-life of the smart patch by 1-10 years.

195. The method of any one of claims 180-194, wherein the biocompatible layer is configured to shield the smart patch from active pharmaceutical ingredient (API) vapors.

196. The method of any one of claims 113-120 or 139-195, wherein the flex circuit is made of a material comprising one or more substances present at sufficiently low levels to be compliant with the Restriction of Hazardous Substances Directive (RoHS).

197. The method of claim 196, wherein the one or more substances comprises Lead (Pb), Mercury (Hg), Cadmium (Cd), Hexavalent Chromium (Cr VI), Polybrominated Biphenyls (PBB), Polybrominated Diphenyl Ethers (PBDE), Bis(2-ethylhexyl) phthalate (DEHP),WSGR Attorney Docket No. 65297-702.601Benzyl butyl phthalate (BBP), Dibutyl phthalate (DBP), Diisobutyl phthalate (DIBP) or any combination thereof.

198. The method of any one of claims 113-197, further comprising alerting the patient and / or one or more caregivers of an upcoming dose, an overdose, an underdose, a missed dose, a mistimed dose, or any combination thereof.

199. The method of any one of claims 113-198, wherein the processor is configured to run a command-based engine.

200. The method of claim 199, wherein the command-based engine is configured to control the one or more sensors.

201. The method of claim 199 or claim 200, wherein the command-based engine is configured to manage connectivity with the Internet of Things or a local server.

202. The method of any one of claims 133-201, wherein the processor is configured to run a rule engine.

203. The method of claim 202, wherein the rule engine is configured to monitor a multistage data ingestion pipeline.

204. The method of any one of claims 113-203, wherein the processor is configured to run a layered script engine.

205. The method of claim 204, wherein the layered script engine is configured to dynamically select protocol sequences based on a source of information comprising a gateway status or a power state.

206. The method of any one of claims 113-205, wherein the processor is configured to run an adaptive sensor fusion engine.

207. The method of claim 113-206, wherein the adaptive sensor fusion engine is configured to use time-aware, context-based logic to integrate sensor evaluation.

208. The method of any one of claims 113-207, wherein the user interface is configured to output the smart patch status data.WSGR Attorney Docket No. 65297-702.601209. The method of claim 208, wherein the user interface is configured to output the smart patch status data in a format comprising a medication regimen.

210. The method of claim 208 or claim 209, wherein the user interface is configured to output the smart patch status data in a format comprising a smart patch replacement schedule.

211. The method of any one of claims 208-210, wherein the user interface is configured to output the smart patch status data in a format comprising an adherence record.

212. The method of any one of claims 208-211, wherein the user interface is configured to output the smart patch status data in a format comprising a visual or auditory alert of an upcoming dose, an overdose, an underdose, a missed dose, a mistimed dose, or any combination thereof.

213. The method of any one of claims 133-212, wherein the user interface is configured to display three to seven temporal phases of drug dosing.

214. The method of claim 213, wherein the user interface is configured to display three temporal phases of drug dosing.

215. The method of claim 213, wherein the user interface is configured to display four temporal phases of drug dosing.

216. The method of claim 213, wherein the user interface is configured to display five temporal phases of drug dosing.

217. The method of claim 213, wherein the user interface is configured to display six temporal phases of drug dosing.

218. The method of claim 213, wherein the user interface is configured to display seven temporal phases of drug dosing.

219. The method of claim 213, wherein the three to seven temporal phases are categorized by color.

220. The method of any one of claims 113-219, wherein the user interface is configured to display a list of one or more medicines to be taken during a specific time window.WSGR Attorney Docket No. 65297-702.601221. The method of claim 220, wherein the user interface is configured to display a brand name or a generic name of the one or more medicines.

222. The method of claim 220 or claim 221, wherein the list of one or more medicines is categorized by medical condition.

223. The method of any one of claims 113-222, wherein the transmitting or the outputting occurs through a wireless communication mechanism.

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