Analyte and Environmental Sensors

Abstract

Apparatus, systems and methods are disclosed for in vivo monitoring of local environmental conditions in a patient-user by measuring analytes including glucose, oxygen and / or other analytes. In some embodiments, the sensor device comprises a wafer-based substrate, comprising a working electrode and a reference electrode on the substrate, and at least one electrochemical sensor two-electrode temporary component configured to detect a target analyte in a bodily fluid when the sensor device is deployed in a subject's body, the working electrode being functionalized with a chemical layer configured to promote a reaction involving the target analyte that generates an electrical signal, and an electronic unit in communication with the electrochemical sensor electrodes, providing that the working electrode is functionalized with a chemical layer configured to promote a reaction involving the target analyte that generates an electrical signal, and transmitting the electrical signal to an external processor.

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS All applications filed with this application for which a claim of foreign or domestic priority is identified in the Application Data Sheet are hereby incorporated by reference.

[0002] The present disclosure relates to sensors for monitoring one or more biomarkers and environmental conditions in vitro, ex vivo, or in vivo. [Background technology]

[0003] There is a need for improved sensors, as well as systems and methods, for monitoring one or more biomarkers and environmental conditions in vitro, ex vivo, or in vivo. The present disclosure addresses those needs. Summary of the Invention

[0004] Briefly, devices, systems, and methods are disclosed for monitoring and / or characterizing one or more parameters of bodily fluids from a patient in vivo or ex vivo or in vitro. For example, bodily fluids present in the local environment of a patient user in which a device of the present disclosure is implanted and / or placed. As another example, the bodily fluids may be present in an analytical, e.g., laboratory, instrument, and thus the sensors, apparatus, and systems are used in an in vitro setting. Although the devices, systems, and methods may be described herein in the context of in vivo analysis, the devices and systems are also applicable to ex vivo and in vitro analysis.

[0005] In one embodiment, the device is intended to be at least partially implanted into a patient-user to measure one or more parameters associated with a substance and / or condition of the local environment in which the device is deployed, and may be referred to as an in vivo analytical and environmental sensor device, or more simply as an in vivo sensor device, including an in vivo monitoring device, an in vivo analyte sensor device, an environmental sensor device, an in vivo sensor, an analyte sensor, an environmental sensor, a sensor device, etc. In one embodiment, the device is intended to be implanted entirely within a patient-user to measure one or more parameters associated with a substance and / or condition of the local environment in which the device is deployed. In one embodiment, the device is intended to be positioned on a surface, such as, for example, the skin of a patient-user, to measure one or more parameters associated with a substance and / or condition of the local environment in which the device is deployed. For example, the sensor device may detect and / or measure the concentration of an analyte (i.e., the substance being identified and / or measured) in the local environment, such as, for example, glucose, oxygen, ketones, and / or other analytes. The description of the present technology primarily refers to in vivo sensor devices that measure parameters or characteristics of analytes to illustrate the environmental sensors of the present disclosure, which may also be deployed ex vivo. The technology disclosed herein is applicable to monitoring environmental parameters other than analyte identity and concentration. For example, the device may detect and / or measure the temperature of the local in vivo environment, which may indicate a biological condition such as infection. As another example, the device may measure the osmolality and / or osmolality of a fluid in contact with an implanted in vivo environmental sensor.

[0006] Disclosed are devices, systems, and methods for in vivo or ex vivo monitoring of local environmental conditions in or on a patient-user by measuring analytes, including, for example, glucose, oxygen, and / or other analytes. In some embodiments, the sensor device includes a wafer-based substrate and at least one electrochemical two-electrode sensor having a working electrode and a reference electrode on the substrate and configured to detect a target analyte in a bodily fluid. The sensor device may be placed in the subject's body. The sensor device may be deployed on the subject's body. The working electrode is functionalized with a chemical layer configured to promote a reaction involving the target analyte that generates an electrical signal. The sensor device may also have an electronic unit in communication with the electrochemical sensor electrode, providing for transmitting the electrical signal to an external processor.

[0007] Below are some exemplary embodiments of the present disclosure, numbered for convenience. 1) A sensor device for monitoring an analyte, comprising: a substrate comprising a non-conductive material; an electrochemical sensor electrode disposed on the substrate and configured to detect a target analyte in a bodily fluid when the electrochemical sensor electrode is fully deployed within a body of a subject; and a working electrode, which is a temporary part of the electrochemical sensor electrode, and optionally a reference electrode associated with the working electrode, wherein the working electrode is functionalized with a chemical layer configured to promote a reaction involving the target analyte that generates an electrical signal at the electrochemical sensor electrode, and optionally and an electronic unit in communication with the electrochemical sensor electrode temporary arrangement, the electronic unit comprising a wireless communication unit including a wireless transmitter or transceiver for transmitting data associated with the electrical signal to an external processor, e.g., the sensor device is for in vivo monitoring and includes the optional electronic unit, or the sensor device is for ex vivo monitoring and includes the optional electronic unit, or the sensor device is for in vivo monitoring and does not necessarily include the electronic unit, or the sensor device is for ex vivo monitoring and does not necessarily include the electronic unit.

[0008] 2) The sensor device of embodiment 1, wherein the processor is operable to determine a parameter associated with the target analyte based on the electrical signal measured at the time of the electrochemical sensor electrode, and the processor is configured to temporarily determine a change in environmental condition within a deployment zone from the same electrical signal generated at the electrochemical sensor electrode when the electrochemical sensor electrode is deployed within a subject's body.

[0009] 3) The sensor device of embodiment 2, wherein the change in environmental condition includes one or more of a change in temperature, a change in moisture, or a change in osmotic pressure.

[0010] 4) A sensor device as described in embodiment 2, wherein the change in environmental condition includes a change in temperature, and the determined change in temperature indicates temperature stability within the deployment zone and potential infection at least within or near the deployment zone. 5) The sensor device of embodiment 2, wherein the change in environmental condition includes a change in temperature, and the determined change in temperature is information about a change in magnitude of temperature within the deployment zone.

[0011] 6) A sensor device according to any one of embodiments 2 to 5, wherein the determined change in temperature is compared to a threshold and an alarm is generated when the determined change exceeds the threshold.

[0012] 7) The sensor device of embodiment 2, wherein the change in environmental condition comprises a change in osmotic pressure, and the determined change in osmotic pressure indicates the stability of the salt concentration in the placement zone and potential dehydration at least in or near the placement zone.

[0013] 8) The sensor device of embodiment 7, wherein the determined change in osmotic pressure is compared to a threshold value and an alarm is generated when the determined change exceeds the threshold value.

[0014] 9) A sensor device according to embodiment 1, a plurality of electrodes disposed on the substrate and configured to detect a parameter associated with the electrical conductivity of the bodily fluid across at least two of the plurality of electrodes when the sensor device is deployed within the subject's body.

[0015] 10) A sensor device as described in embodiment 9, wherein at least two electrodes are configured to operate as an AND gate, such that when bodily fluid is in contact with both of the two electrodes, a short circuit occurs across the two electrodes corresponding to one of the AND gates and one signal detectable by the sensor device.

[0016] 11) A sensor device according to any of embodiments 9 or 10, wherein at least some of the electrodes are at least partially covered by a permeable membrane.

[0017] 12) The sensor device of embodiment 1, wherein the substrate comprises a top surface having a plurality of ridges to provide the sensor device with a three-dimensional profile.

[0018] 13) The sensor device of embodiment 12, wherein the substrate is a wafer-based substrate comprising at least one of silicon oxide, germanium, or gallium arsenide.

[0019] 14) A sensor device according to any of embodiments 12 or 13, wherein the electrochemical sensor electrodes have a shape corresponding to a three-dimensional profile.

[0020] 15) The sensor device of embodiment 14, wherein the working electrode and the reference electrode are disposed on at least a portion of one or more of the plurality of ridges of the substrate.

[0021] 16) A sensor device described in any of embodiments 12 or 13, wherein the chemical layer has a morphology corresponding to a three-dimensional profile.

[0022] 17) The sensor device of embodiment 1, wherein the reference electrode comprises iridium.

[0023] 18) The sensor device of embodiment 17, wherein the reference electrode comprises iridium oxide.

[0024] 19) A sensor device described in any of embodiments 17 or 18, wherein the sensor device is capable of maintaining a constant and stable reference signal for the detected electrical signal for at least 12 months.

[0025] 20) A sensor device according to any of embodiments 17 or 18, wherein the sensor device is operable to detect a target analyte with low power consumption based on an applied voltage at the reference electrode of less than 300mV, or less than 285mV, or less than 175mV.

[0026] 21) A sensor device as described in any of embodiments 17 or 18, wherein the sensor device is configured to prevent detectable interference signals caused by secondary chemical elements including dopamine, aspirin, acetaminophen, numbing chemicals for pain treatment, or others.

[0027] 22) The sensor device of embodiment 1, wherein the working electrode comprises at least one of platinum, iridium, gold, silver, titanium, single-walled or multi-walled carbon nanotubes, or an alloy.

[0028] 23) The sensor device of embodiment 22, wherein the working electrode comprises platinum and iridium.

[0029] 24) The sensor device of embodiment 1, wherein the working electrode is functionalized with a chemical layer configured to promote a reaction that results in a change in charge potential or flow at or near the working electrode such that an electrical signal associated with the reaction is detectable at the working electrode relative to a reference electrode to measure a parameter associated with the target analyte.

[0030] 25) The sensor device of embodiment 24, comprising a membrane, wherein the chemical layer comprises: (i) an outer layer exposed to bodily fluids configured to regulate permeation of reactive species comprising a target analyte; and (ii) an inner layer coupled between the outer layer and a surface of the working electrode to immobilize a catalyst capable of promoting a reaction with the permeating reactive species for detection of the target analyte at the working electrode.

[0031] 26) A sensor device as described in embodiment 24, wherein the chemical layer comprises a membrane including (i) an outer layer exposed to the body fluid configured to regulate the permeation of reactive species including the target analyte, and (ii) an inner layer bonded between the outer layer and the surface of the working electrode to immobilize a catalyst capable of promoting the reaction by the permeating reactive species for detection of the target analyte at the working electrode, wherein the membrane comprises a plurality of corrugations on an upper surface of the outer layer.

[0032] 27) A sensor device according to embodiment 26, wherein the membrane has a thickness of less than 10 μm or between 5 μm and 10 μm.

[0033] 28) The sensor device of embodiment 26, wherein the plurality of corrugations on the top surface of the outer layer include a height in the range of 10 μm to 20 μm.

[0034] 29) The sensor device of embodiment 26, wherein the plurality of corrugations on the top surface of the outer layer are configured to promote the functional life of the electrochemical sensor electrode based on increasing the signal stability of the detected electrical signal and preventing fouling of the working electrode.

[0035] 30) A sensor device described in any of embodiments 26 to 29, wherein the multiple corrugations of the membrane are at least partially formed by the membrane conformed onto the three-dimensional surface of the substrate.

[0036] 31) The sensor device of embodiment 1, wherein the electronic unit further comprises a signal conditioning unit in communication with the electrochemical sensor electrodes via one or more electrical interface components, the signal conditioning unit comprising electrical circuitry configured to process the detected electrical signal by one or more of amplifying the electrical signal, filtering the electrical signal, or converting the electrical signal from analog to digital.

[0037] 32) The sensor device of embodiment 31, wherein the electronic unit further comprises a data processing unit in communication with the signal conditioning unit, the data processing unit comprising a processor and a memory and configured to process the electrical signal as analyte data representative of one or more parameters of the target analyte.

[0038] 33) A sensor device as described in embodiment 1, comprising electrical interconnection wires and electrical interface contact sites disposed on the substrate, the electrical interconnection wires being coupled between the electrochemical sensor electrodes and the electrical interface contact sites.

[0039] 34) The sensor apparatus of embodiment 33, wherein the electrical interconnect wires disposed on the substrate are sealed by a non-permeable material that covers the electrical interconnect wires and provides an electrical shield from the body fluid.

[0040] 35) The sensor device of embodiment 34, wherein the non-permeable material comprises at least one of a parylene, a urethane, or a Teflon material.

[0041] 36) A sensor device as described in embodiment 1, comprising a casing that encases the electronic unit and protects it from exposure to bodily fluids and at least partially encases the electrochemical sensor electrodes such that the working electrode and reference electrode are exposed to bodily fluids when the sensor device is deployed in a subject's body.

[0042] 37) A sensor device as described in embodiment 36, wherein the casing includes one or both of flat or curved sides to provide a form factor for the sensor device.

[0043] 38) The sensor device of embodiment 36, wherein the sensor device factors include at least one of a rectangular, cylindrical, conical, elliptical, pyramidal, trapezoidal, or non-uniform shape.

[0044] 39) A sensor device according to embodiment 1, a second electrochemical sensor electrode disposed on the substrate and configured to detect a second target analyte in the bodily fluid when the second electrochemical sensor electrode is fully deployed within the subject's body; the second electrochemical sensor electrode part and optionally a second working electrode and a second reference electrode associated with the second working electrode, the second working electrode being functionalized with a second chemical layer configured to promote a reaction involving the second target analyte that generates a second electrical signal at the second electrochemical sensor electrode part.

[0045] 40) A sensor device according to embodiment 1, and one or more conductive pads disposed on the substrate configured to be electrically stimulated to detect a parameter associated with the bodily fluid temporarily exposed to the electrochemical sensor electrodes.

[0046] 41) A sensor device as described in embodiment 40, wherein the one or more conductive pads have the ability to ensure that the detected electrical signal is detected in a fluid-rich environment.

[0047] 42) A sensor device as described in embodiment 40, wherein the one or more conductive pads can reduce noise associated with the detected signal to a negligible level.

[0048] 43) The sensor device of any of embodiments 1-42, wherein the target analytes include one or more of glucose, oxygen, ketones, water, amino acids, nucleic acids, lipids, proteins, carbohydrates, liposomes, nanoparticles, or pharmacological drugs.

[0049] 44) A sensor device according to any one of embodiments 1 to 43, wherein the sensor device is configured to detect the target analyte as a primary biomarker indicative of a health state of the subject and to detect a secondary biomarker simultaneously with the primary biomarker, the secondary biomarker comprising a physiological parameter comprising one or both of temperature and vibration, and the physiological parameter being detected based on a signal analysis of the detected electrical signal by the electrochemical sensor electrode.

[0050] 45) A sensor device described in any of embodiments 1 to 44, wherein the sensor device is operable to be inserted beneath the subcutaneous layer of a subject and within an interstitial pocket of the subject, such that the sensor can detect and determine whether there is a sufficient pool of interstitial fluid within the interstitial pocket to obtain an electrical signal associated with a target analyte.

[0051] 46) A sensor device for in vivo monitoring of an analyte, comprising: a substrate comprising a non-conductive material, said substrate being a wafer-based substrate comprising silicon oxide, said substrate comprising a top surface having a plurality of ridges for providing a three-dimensional profile for said sensor device; an electrochemical sensor electrode disposed on the substrate and configured to detect a target analyte in a bodily fluid when the electrochemical sensor electrode is fully deployed within a body of a subject; a temporary part of the electrochemical sensor electrode, and optionally a working electrode and a reference electrode associated with the working electrode, the electrochemical sensor electrode temporary part having a form corresponding to the three-dimensional profile provided by the substrate, the working electrode is functionalized with a chemical layer configured to promote a reaction involving the target analyte that generates an electrical signal at the electrochemical sensor electrode temporary part, the reference electrode comprises iridium oxide, and the working electrode comprises platinum and iridium, the sensor device is operable to detect the target analyte with low power consumption based on an applied voltage at the reference electrode of less than 300mV, or less than 285mV, or less than 175mV; the chemical layer comprises a membrane including: (i) an outer layer exposed to the bodily fluid configured to regulate permeation of reactive species including the target analyte; and (ii) an inner layer coupled between the outer layer and the surface of the working electrode to immobilize a catalyst capable of facilitating the reaction by the permeating reactive species for detection of the target analyte at the working electrode, the membrane including a plurality of corrugations on an upper surface of the outer layer; a plurality of electrodes disposed on the substrate and configured to detect a parameter associated with electrical conductivity of the bodily fluid across at least two of the plurality of electrodes when the sensor device is deployed within the subject's body, the at least two electrodes configured to operate as an AND gate, such that when the bodily fluid contacts both of the two electrodes, a short circuit occurs across the two electrodes corresponding to one of the AND gates and a signal detectable by the sensor device; and an electronic unit in communication with the electrochemical sensor electrode temporary device, the electronic unit comprising a wireless communication unit including a wireless transmitter or transceiver for transmitting data associated with the electrical signal to an external processor; wherein the processor is operable to determine a parameter associated with the target analyte based on the electrical signal measured at the electrochemical sensor electrode, and the processor is configured to determine from the same electrical signal generated at the electrochemical sensor electrode a change in environmental conditions, including temperature, within a deployment zone when the electrochemical sensor electrode is deployed within the subject's body.

[0052] 47) The sensor device of embodiment 46, wherein the sensor device includes one or more features recited in any of embodiments 2 to 45.

[0053] 48) A sensor device for in vivo monitoring of an analyte, comprising: a substrate comprising a non-conductive material; an electrochemical sensor electrode disposed on the substrate and configured to detect a target analyte in a bodily fluid when the electrochemical sensor electrode is fully deployed within a subject's body; and optionally a working electrode and a reference electrode that are part of the electrochemical sensor electrode, the working electrode being functionalized with a chemical layer configured to promote a reaction involving the target analyte that generates an electrical signal at the electrochemical sensor electrode.

[0054] 49) The sensor device of embodiment 48, wherein the sensor device includes one or more features recited in any of embodiments 2 to 45.

[0055] 50) A sensor device for in vivo monitoring of an analyte, comprising: a substrate comprising a non-conductive material; an electrochemical sensor electrode disposed on the substrate and configured to detect a target analyte in a bodily fluid when the electrochemical sensor electrode is fully deployed within a subject's body, the electrochemical sensor electrode including a working electrode and a reference electrode associated with the working electrode, the working electrode functionalized with a chemical layer configured to promote a reaction involving the target analyte that generates an electrical signal at the electrochemical sensor electrode, and optionally, the reference electrode comprises iridium.

[0056] 51) A sensor device as described in embodiment 50, wherein the sensor device includes one or more features recited in any of embodiments 2 to 45.

[0057] 52) A system for analyte and environmental sensing, comprising: a sensor device operable to be deployed at least partially within a patient-user's body; The sensor device comprises: a substrate comprising a non-conductive material; an electrochemical sensor electrode disposed on the substrate and configured to detect a target analyte in a bodily fluid when the electrochemical sensor electrode is fully deployed within a patient-user's body; a working electrode that is a temporary part of the electrochemical sensor electrode, and optionally a reference electrode associated with the working electrode; the working electrode is functionalized with a chemical layer configured to promote a reaction involving the target analyte that generates an electrical signal at the electrochemical sensor electrode; and an electronic unit in communication with the electrochemical sensor electrodes, the electronic unit comprising a wireless communication unit including a wireless transmitter or transceiver for transmitting data associated with the electrical signal to an external processor; and a data processing system including a processor and memory configured to be in data communication with the sensor device, receive the data from the sensor unit, and process the received data to indicate parameters associated with the target analyte and / or environmental conditions in an area in which the electrochemical sensor electrode temporary apparatus is deployed.

[0058] 53) The system described in embodiment 52, wherein the sensor device includes one or more features associated with the sensor device listed in any of embodiments 1 to 45, any of embodiments 46 to 47, any of embodiments 48 to 49, and / or any of embodiments 50 to 51.

[0059] 54) The system described in embodiment 52, wherein the data processing system includes a server computer having a processor and memory, and one or more databases in data communication with the server computer, and the data processing system is configured to remotely monitor data associated with a patient-user acquired by the sensor device.

[0060] 55) The system according to embodiment 52, A system comprising: a receiver apparatus, including a processor and a memory, operable to: (i) receive a wireless transmission carrying data indicative of the electrical signal obtained from the sensor device; and (ii) transmit the data to the data processing system.

[0061] 56) The system of embodiment 55, wherein the receiver device is configured to store data in a memory of the receiver device.

[0062] 57) The system of embodiment 55, wherein the receiver devices communicate with each other and with the data processing system via a network of computers accessible via the Internet.

[0063] 58) The system according to embodiment 52, a remote client computing device having a processor and memory, in data communication with the data processing system, and configured to receive processed data that has been selected, filtered, and / or formatted by the data processing system.

[0064] 59) A device, system, or method for in vivo monitoring of at least one analyte and at least one analyte in conjunction with the at least one analyte and a secondary phenomenon, including temperature, according to the disclosure of this patent document.

[0065] 60) A sensor device for monitoring an analyte, the sensor device comprising: a substrate comprising a non-conductive material; an electrochemical sensor electrode disposed on said substrate and configured to detect a target analyte, said electrochemical sensor electrode comprising, and optionally consisting of exactly two electrodes, said two electrodes being a working electrode and a reference electrode; the working electrode is functionalized with a chemical layer configured to promote a reaction involving the target analyte that generates an electrical signal at the electrochemical sensor electrode; The method of claim 1, wherein the reference electrode comprises a layer of iridium metal and a layer of iridium oxide.

[0066] 61) The sensor device of embodiment 60, wherein the substrate is a planar wafer comprising silicon dioxide.

[0067] 62) The sensor device of embodiment 60, wherein the target analyte is glucose and the working electrode comprises glucose oxidase.

[0068] 63) The sensor device of embodiment 60, wherein the working electrode comprises a layer of platinum metal and a layer of titanium metal, the layer of titanium metal being located between the substrate and the layer of platinum metal.

[0069] 64) The sensor device of embodiment 60, wherein the working electrode comprises a layer of platinum metal and a layer of titanium metal, the layer of titanium metal being located between the substrate and the layer of platinum metal, the layer of titanium metal containing at least 95% by weight titanium metal based on the weight of the titanium layer, and the layer of platinum metal containing at least 95% by weight platinum based on the weight of the platinum layer.

[0070] 65) The sensor device of embodiment 60, wherein the working electrode contains 5% by weight or less of a metal other than platinum and titanium.

[0071] 66) The sensor device of embodiment 60, wherein the reference electrode comprises a layer of platinum metal and a layer of titanium metal, the layer of titanium metal being located between the substrate and the layer of platinum metal.

[0072] 67) The sensor device of embodiment 60, wherein the reference electrode comprises a layer of platinum metal and a layer of iridium metal, the layer of platinum metal being located between the substrate and the layer of iridium metal.

[0073] 68) The sensor device of embodiment 60, wherein the reference electrode comprises a layer of iridium metal and a layer of iridium oxide, the layer of iridium metal being located between the substrate and the layer of iridium oxide.

[0074] 69) The sensor device of embodiment 60, wherein the reference electrode comprises a layer of titanium metal in direct contact with the substrate, a layer of platinum metal in direct contact with the layer of titanium metal, a layer of iridium metal in direct contact with the layer of platinum metal, and a layer of iridium oxide in direct contact with the layer of iridium metal.

[0075] 70) A sensor device according to embodiment 60, a. the substrate is a wafer comprising silicon dioxide; b. the working electrode comprises a layer of titanium metal in direct contact with the substrate, a layer of platinum metal in direct contact with the layer of titanium metal, and a chemistry layer including glucose oxidase configured to promote a reaction with glucose that generates an electrical signal at the electrochemical sensor electrode; c. The method of treating a substrate as described in claim 1, wherein the reference electrode comprises: a layer of titanium metal in direct contact with the substrate; a layer of platinum in direct contact with the layer of titanium metal; a layer of iridium metal in direct contact with the layer of titanium metal; and a layer of iridium oxide in direct contact with the layer of iridium metal.

[0076] 71) A sensor device as described in embodiment 60, further comprising one or more features as described in any of embodiments 2 to 45.

[0077] 72) A sensor device described in any of embodiments 61 to 69, further including one or more features recited in any of embodiments 2 to 45.

[0078] 73) A sensor device as described in embodiment 70, further comprising one or more features as described in any one of embodiments 2 to 45.

[0079] 74) A sensor device as described in embodiment 60, wherein the processor is operable to determine a parameter associated with the target analyte based on the electrical signal measured at the time of the electrochemical sensor electrode, and the processor is configured to temporarily determine a change in environmental condition within the deployment zone from the same electrical signal generated at the electrochemical sensor electrode when the electrochemical sensor electrode is deployed within the subject's body.

[0080] 75) The sensor device of embodiment 60, wherein the change in environmental condition includes one or more of a change in temperature, a change in moisture, or a change in osmotic pressure.

[0081] 76) A sensor device as described in embodiment 60, wherein the change in environmental condition includes a change in temperature, and the determined change in temperature indicates temperature stability within the deployment zone and at least a potential infection within or near the deployment zone.

[0082] 77) A sensor device as described in embodiment 60, wherein the change in environmental condition includes a change in temperature, and the determined change in temperature is information about a change in magnitude of temperature within the deployment zone.

[0083] 78) A sensor device described in any of embodiments 74 to 77, wherein the determined change in temperature is compared to a threshold value and an alarm is generated when the determined change exceeds the threshold value.

[0084] 79) A sensor device described in any of embodiments 1 to 78, wherein the target analyte includes one or more of glucose, oxygen, ketones, water, amino acids, nucleic acids, lipids, proteins, carbohydrates, liposomes, nanoparticles, or pharmacological drugs.

[0085] 80) A sensor device as described in any of embodiments 1 to 78, wherein the sensor device is configured to detect the target analyte as a primary biomarker indicative of a health state of the subject and to detect a secondary biomarker simultaneously with the primary biomarker, the secondary biomarker comprising a physiological parameter including one or both of temperature and vibration, and the physiological parameter is detected based on a signal analysis of the detected electrical signal by the electrochemical sensor electrode. The electrochemical sensor electrode of claim 1.

[0086] 81) A sensor device described in any of embodiments 1 to 78, wherein the sensor device is operable to be inserted beneath the subcutaneous layer of a subject and within an interstitial pocket of the subject, and wherein the sensor is capable of detecting and determining whether there is a sufficient pool of interstitial fluid within the interstitial pocket to obtain an electrical signal associated with a target analyte.

[0087] 82) A sensor device according to embodiment 60, a substrate comprising a non-conductive material, said substrate being a wafer-based substrate comprising silicon oxide, said substrate comprising a top surface having a plurality of ridges for providing a three-dimensional profile for said sensor device; an electrochemical sensor electrode disposed on the substrate and configured to detect a target analyte in the bodily fluid when the electrochemical sensor electrode temporary part is in contact with the bodily fluid, the electrochemical sensor electrode temporary part having a form corresponding to the three-dimensional profile provided by the substrate, the working electrode is functionalized with a chemical layer configured to promote a reaction involving the target analyte that generates an electrical signal at the electrochemical sensor electrode temporary part, the reference electrode comprises iridium oxide, and the working electrode comprises platinum and iridium, the sensor device is operable to detect the target analyte with low power consumption based on an applied voltage at the reference electrode of less than 300mV, or less than 285mV, or less than 175mV, the chemical layer comprises a membrane including: (i) an outer layer exposed to the bodily fluid configured to regulate permeation of reactive species including the target analyte; and (ii) an inner layer coupled between the outer layer and the surface of the working electrode to immobilize a catalyst capable of facilitating the reaction by the permeating reactive species for detection of the target analyte at the working electrode, the membrane including a plurality of corrugations on an upper surface of the outer layer; a plurality of electrodes disposed on the substrate and configured to detect a parameter associated with electrical conductivity of the bodily fluid across at least two of the plurality of electrodes when the sensor device is deployed within the subject's body, the at least two electrodes configured to operate as an AND gate, such that when the bodily fluid contacts both of the two electrodes, a short circuit occurs across the two electrodes corresponding to one of the AND gates and a signal detectable by the sensor device; and an electronic unit in communication with the electrochemical sensor electrode temporary device, the electronic unit comprising a wireless communication unit including a wireless transmitter or transceiver for transmitting data associated with the electrical signal to an external processor; The apparatus, wherein the processor is operable to determine a parameter associated with the target analyte based on the electrical signals measured at the electrochemical sensor electrodes.

[0088] 83) The sensor device of embodiment 82, wherein the sensor device includes one or more features recited in any of embodiments 2 to 45.

[0089] 84) A sensor device for monitoring an analyte, comprising: a substrate comprising a non-conductive material; an electrochemical sensor electrode disposed on the substrate and configured to detect a target analyte in a bodily fluid when the electrochemical sensor electrode is in contact with the bodily fluid, the working electrode being a temporary part of the electrochemical sensor electrode, and optionally a working electrode and a reference electrode associated with the working electrode, wherein the working electrode is functionalized with a chemical layer configured to promote a reaction involving the target analyte that generates an electrical signal at the electrochemical sensor electrode.

[0090] 85) A sensor device as described in embodiment 84, wherein the sensor device includes one or more features recited in any of embodiments 2 to 45.

[0091] 86) A sensor device for monitoring an analyte, comprising: a substrate comprising a non-conductive material; an electrochemical sensor electrode disposed on the substrate and configured to detect a target analyte in the bodily fluid when the electrochemical sensor electrode contacts the bodily fluid, the electrochemical sensor electrode including a working electrode and a reference electrode associated with the working electrode, the working electrode functionalized with a chemical layer configured to promote a reaction involving the target analyte that generates an electrical signal at the electrochemical sensor electrode, and optionally the reference electrode comprises iridium.

[0092] 87) A sensor device as described in embodiment 86, wherein the sensor device includes one or more features recited in any of embodiments 2 to 45.

[0093] 88) A sensor device described in any one of embodiments 1 to 87, which is sterilized.

[0094] 89) A system for analyte and environmental sensing, comprising: A sensor device as described herein, for example, a sensor device as described in any one of embodiments 1 to 88; The sensor device comprises: a substrate comprising a non-conductive material; an electrochemical sensor electrode disposed on the substrate; a temporary part of the electrochemical sensor electrode configured to detect a target analyte in the bodily fluid when in contact with the bodily fluid, e.g., when the sensor is fully deployed within the patient's body, the temporary part of the electrochemical sensor electrode, and optionally a working electrode and a reference electrode associated with the working electrode, the working electrode being functionalized with a chemical layer configured to promote a reaction with the target analyte that generates an electrical signal at the temporary part of the electrochemical sensor electrode, and an electronic unit in communication with the electrochemical sensor electrodes, the electronic unit comprising a wireless communication unit including a wireless transmitter or transceiver for transmitting data associated with the electrical signal to an external processor; and a data processing system including a processor and memory configured to be in data communication with the sensor device, receive the data from the sensor unit, and process the received data to indicate parameters associated with the target analyte and / or environmental conditions in an area in which the electrochemical sensor electrode temporary apparatus is deployed.

[0095] 90) The system described in embodiment 89, wherein the sensor device includes one or more features associated with the sensor device listed in any of embodiments 1 to 88.

[0096] 91) The system described in embodiment 89, wherein the data processing system includes a server computer having a processor and memory, and one or more databases in data communication with the server computer, and the data processing system is configured to remotely monitor data associated with a patient-user acquired by the sensor device.

[0097] 92) The system according to embodiment 89, A system comprising: a receiver apparatus, including a processor and a memory, operable to: (i) receive a wireless transmission carrying data indicative of the electrical signal obtained from the sensor device; and (ii) transmit the data to the data processing system.

[0098] 93) The system of embodiment 92, wherein the receiver device is configured to store data in a memory of the receiver device.

[0099] 94) The system of embodiment 92, wherein the receiver devices communicate with each other and with the data processing system via a network of computers accessible via the Internet.

[0100] 95) The system according to embodiment 89, a remote client computing device having a processor and memory, in data communication with the data processing system, and configured to receive processed data that has been selected, filtered, and / or formatted by the data processing system.

[0101] 96) A device, system, or method for in vivo monitoring of at least one analyte and at least one analyte in conjunction with the at least one analyte and a secondary phenomenon, including temperature, according to the disclosure of this patent document.

[0102] 97) A method for in vivo detection of the presence of an analyte in a biological fluid, the method comprising implanting a sensor device described herein inside a patient, e.g., a sensor device described in any of embodiments 1-88, exposing the sensor device to the biological fluid inside the patient, generating an electrical signal by the sensor device responsive to the presence of the analyte in the biological fluid, converting the electrical signal into an observable indication of the presence of the analyte in the biological fluid, and optionally the sensor device displaying and / or transmitting data associated with the electrical signal.

[0103] 98) A method for detecting the presence of an analyte in a biological fluid ex vivo, the method comprising positioning a sensor apparatus as described herein on a surface of a patient, e.g., a sensor device as described in any of embodiments 1-88, exposing the sensor device to the biological fluid on the surface of the patient, generating an electrical signal by the sensor device responsive to the presence of the analyte in the biological fluid, converting the electrical signal into an observable indication of the presence of the analyte in the biological fluid, and optionally the sensor device displaying and / or transmitting data associated with the electrical signal.

[0104] 99) A method for detecting the presence of an analyte in a biological fluid ex vivo, the method comprising positioning on a biological fluid conduit, e.g., a catheter, a sensor device as described herein, e.g., a sensor device as described in any of embodiments 1-88, exposing the sensor device to the biological fluid contained within the biological fluid conduit, generating an electrical signal by the sensor device responsive to the presence of the analyte in the biological fluid, converting the electrical signal into an observable indication of the presence of the analyte in the biological fluid, and optionally the sensor device displaying and / or transmitting data associated with the electrical signal.

[0105] 100) A method for detecting the presence of an analyte in a biological fluid in vitro, the method comprising placing a sensor apparatus as described herein, e.g., a sensor device as described in any of embodiments 1-88, in an in vitro location, exposing the sensor device to the biological fluid at the in vitro location, generating an electrical signal by the sensor device responsive to the presence of the analyte in the biological fluid, converting the electrical signal into an observable indication of the presence of the analyte in the biological fluid, and optionally, the sensor device displaying and / or transmitting data associated with the electrical signal.

[0106] The above-mentioned and additional features of the invention, and the manner of obtaining them, will become apparent and the invention will be best understood by reference to the following more detailed description, in which: All references disclosed herein are incorporated by reference in their entirety as if each were individually incorporated.

[0107] This Summary is provided to introduce certain concepts in a simplified form that are described in more detail below in the Detailed Description. Unless expressly stated otherwise, this Summary is not intended to identify key or essential features of the claimed subject matter, nor is it intended to limit the scope of the claimed subject matter.

[0108] Details of one or more embodiments are set forth in the following description. Features illustrated or described in connection with one exemplary embodiment may be combined with features of other embodiments. Thus, any of the various embodiments described herein can be combined to provide further embodiments. Aspects of the embodiments can be modified, as necessary, to employ concepts of the various patents, applications, and publications identified herein to provide further embodiments. Other features, objects, and advantages will be apparent from the description, drawings, and claims.

[0109] Many aspects of the present disclosure can be better understood with reference to the following drawings. Features in the drawings are not necessarily shown to scale or in the same manner as they are physically constructed. Emphasis instead is placed on clearly illustrating the principles of the present disclosure. The drawings should not be taken to limit the disclosure to the specific embodiments illustrated, but are for purposes of explanation and understanding only. [Brief description of the drawings]

[0110] [Figure 1A] FIG. 1 shows a diagram illustrating an exemplary embodiment of a system for monitoring one or more analytes of a user in accordance with the present technology. [Figure 1B] FIG. 1B is a block diagram illustrating an exemplary embodiment of the analyte sensor of FIG. 1A in accordance with the present technology. [Figure 1C] FIG. 1 shows a block diagram illustrating an exemplary embodiment of a sensor unit for an analyte sensor in accordance with the present technology. [Figure 2A] FIG. 1 shows a diagram illustrating an exemplary embodiment of a sensor unit for an analyte sensor device including a two-electrode sensor according to the present technology. [Figure 2B] FIG. 1 shows a diagram illustrating an exemplary embodiment of a sensor unit for an analyte sensor device including a three-electrode sensor according to the present technology. [Figure 2C] FIG. 1 shows an exemplary embodiment of a sensor unit for an analyte sensor device including a plurality of two-electrode sensors in accordance with the present technology. [Diagram 3] 1 shows a diagram of another exemplary embodiment of a sensor unit for an analyte sensor device in accordance with the present technology. [Figure 4] 1 shows a diagram of another exemplary embodiment of a sensor unit for an analyte sensor device in accordance with the present technology. [Diagram 5] FIG. 1 shows a diagram illustrating a method 500 for deploying and activating an independent analyte sensor device 100 in a subject in accordance with the present technology. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0111] Disclosed are devices, systems, and methods for ex vivo and in vivo and in vitro monitoring of one or more parameters of a patient's bodily fluids, such as the local environment of a patient in which a device of the present disclosure is implanted or on which it is implanted. In one embodiment, the device is intended to be at least partially implanted in a patient user to measure one or more parameters related to substances and / or conditions of the local environment in which the device is deployed, and may be referred to as an in vivo analyte and environmental sensor device, or more simply as an in vivo sensor device, including an in vivo monitoring device, including an in vivo analyte sensor device, including an environmental sensor device, including an in vivo sensor, including an analyte sensor, including an environmental sensor, including a sensor device, etc. For example, a sensor device may detect and / or measure the concentration of an analyte (i.e., a substance to be identified and / or measured) in the local environment, such as, for example, glucose, oxygen, ketones, and / or other analytes. Although the description of the present technology primarily describes the environmental sensors of the present disclosure utilizing in vivo sensor devices that measure analyte parameters or characteristics, the technology disclosed herein is applicable to monitoring environmental parameters in ex vivo or in vitro formats. For example, the device may detect and / or measure the temperature of the local in vivo or ex vivo environment, which may indicate a biological condition such as infection. As another example, the device may measure the osmolality and / or osmolality of a fluid in contact with an implanted in vivo environmental sensor.

[0112] In vivo monitoring devices according to the present technology may include fully implantable or partially implantable devices in which at least the electrodes of the in vivo monitoring device are inserted into the body of a human or non-human subject to measure one or more target analytes, i.e., substances having characteristics that can be identified and / or measured. Ex vivo monitoring devices according to the present technology may include devices in which at least the electrodes of the monitoring device are located on the surface of the body of a human or non-human subject to measure one or more target analytes, i.e., substances having characteristics that can be identified and / or measured. As mentioned above, the sensor device may be referred to herein as suitable for in vivo monitoring, but the sensor device may also be suitable for ex vivo or in vitro monitoring. Terms such as subject, patient, user, patient-user, etc. are used interchangeably herein.

[0113] In some aspects, the disclosed devices, systems, and methods include a sensor unit, e.g., an in vivo sensor unit or an ex vivo sensor unit, that includes a substrate having a pattern of electrodes. For example, the substrate may include an electrically insulating (non-conductive) material, and in some embodiments, may be a wafer-based substrate, i.e., a rigid substrate that includes a semiconductor material, such as a crystalline silicon material or an amorphous (non-crystalline) silicon material. The pattern of electrodes includes at least one electrochemical sensor electrode assembly (also referred to herein as an electrochemical sensor electrode adjunct) that includes at least one working electrode and at least one reference electrode. The electrochemical sensor electrode adjunct may optionally include one or more additional electrodes, e.g., additionally include a counter electrode or other electrode for electrochemical sensing. In some embodiments, the pattern of electrodes associated with the substrate may include one, two, three, etc., electrochemical sensor electrodes adjuncts, each having at least one working electrode and at least one reference electrode, and optionally additional electrode(s). The electrochemical sensor electrode adjuncts are components of the sensor units described herein. If the pattern of the electrochemical sensor electrodes is a single two-electrode temporary electrode having a working electrode and a reference electrode, the electrochemical sensor electrodes may be referred to as two-electrode electrochemical sensor temporary electrodes, or more simply as two-electrode sensor temporary electrodes. If the pattern of the electrochemical sensor electrodes is a single three-electrode temporary electrode having a working electrode, a reference electrode, and a counter electrode, the electrochemical sensor electrodes may be referred to as three-electrode electrochemical sensor temporary electrodes, or more simply as three-electrode sensor temporary electrodes.

[0114] In some embodiments, the electrochemical sensor electrodes include a membrane coupled to at least one working electrode to provide a sensing area for facilitating a chemical reaction with one or more target analytes in an in vivo fluid exposed to the pattern of electrodes, and the at least one working electrode on the wafer-based substrate is operable to electrochemically detect a product species of the reaction indicative of an analyte parameter. In some embodiments, the at least one reference electrode comprises iridium (e.g., iridium oxide) and the at least one working electrode comprises iridium and / or platinum (e.g., 90 / 10 platinum / iridium). In some embodiments, the pattern of electrodes provides one or more two-electrode sensor occasion(s) (i.e., the two-electrode sensor occasion does not include a third electrode, e.g., does not include a counter electrode). For example, in some implementations of iridium-based two-electrode sensors, electrodes (e.g., an iridium-containing working electrode and an iridium-containing reference electrode) can be used for long-term analyte monitoring in a subject's body, including for 90 days or more, using low-voltage electrochemical sensing techniques in the range of 110 mV to 175 mV, and the target analyte(s) can be detected at approximately a 150 mV threshold.

[0115] In some embodiments, for example, the sensor unit includes a multiple two-electrode sensor pattern, and the sensor unit is operable to monitor multiple analytes simultaneously, which can be used to determine a physiological factor or condition related to a patient-user, such as, for example, the degree of infection by a foreign body, such as a bacterial infection.

[0116] In some embodiments, the sensor unit includes one or more electrical conductivity sensors including two or more electrodes that can be used to determine the presence of a fluid and / or a fluid property, such as osmolality and / or osmolality. In some embodiments, the electrical conductivity sensor can operate as a switch that generates a distinguishing signal when the presence of a fluid is detected (and / or when coupled with the presence of electrochemical sensor electrodes, a detectable fluid property meets a predetermined threshold), which in some implementations can be used as a control signal for a particular function of the sensor unit.

[0117] In some implementations of the monitoring device of the present disclosure, an exemplary embodiment of the sensor device including a two-electrode sensor unit is operable to detect a parameter of a target analyte (e.g., concentration of the analyte in a fluid) while detecting a change in an environmental condition (e.g., temperature) in a zone or area where the sensor device is located in vivo. As an illustrative example, the disclosed monitoring apparatus can detect the occurrence of a localized infection at an incision site (e.g., a surgical site) from a medical procedure. In an implementation where the medical procedure includes inserting an exemplary embodiment of a two-electrode sensor unit, the in vivo sensor unit can continuously monitor a target analyte (e.g., glucose) in a subject and continuously monitor for changes in temperature (and / or other environmental conditions) indicative of a surgical site infection (SSI) from the same measured signal associated with the monitored target analyte.

[0118] As an example, in some implementations, an analyte sensor device according to the disclosed technology can be configured for in vivo or ex vivo multi-analyte monitoring of glucose and a second analyte, e.g., in a mammal, where the sensed glucose data is processed to generate information regarding the subject's health or disease parameters or conditions, including, but not limited to, diabetes and obesity, as primary outcomes of the information. The sensed glucose with the sensed second analyte data is processed to determine information regarding the subject's nutrient balance, cholesterol, and other factors as secondary outcomes. For example, an exemplary multi-analyte glucose sensor device can be configured to sense oxygen or ketone analytes, and thereby used to monitor the operation of a co-implanted medical device, such as an embolic device (i.e., a device that obstructs fluid flow), to determine whether the embolic device is effectively achieving embolic / clotting body formation and performance in a blood vessel in the body.

[0119] Although the disclosed embodiments of the in vivo analyte sensor are described herein primarily in terms of monitoring the analyte glucose within a patient's body to facilitate understanding of the concepts underlying the present technology, it is understood that the disclosed embodiments according to the present technology may also include monitoring of other analytes, including but not limited to oxygen, ketones, alcohol, water, salts, or other analytes. It is also understood that the in vivo analyte sensor may alternatively be an ex vivo analyte sensor in which a sensor device is disposed on the surface of a subject.

[0120] In some embodiments, a sensor device, for example for monitoring an analyte, comprises a sensor device comprising a substrate comprising a non-conductive material, and an electrochemical sensor electrode disposed on the substrate and configured to detect a target analyte in a bodily fluid upon temporary deployment of the electrochemical sensor electrode (e.g. fully deployed). The temporary part of the electrochemical sensor electrode comprises two electrodes, namely a working electrode and a reference electrode associated with the working electrode, and the working electrode is functionalized with a chemical layer configured to promote a reaction involving the target analyte that generates an electrical signal at the temporary part of the electrochemical sensor electrode. The sensor device may also include an electronic unit in communication with the electrochemical sensor electrode temporary arrangement, the electronic unit comprising a wireless communication unit including a wireless transmitter or a wireless transceiver for at least transmitting an electrical signal to an external processor.

[0121] These and other embodiments are discussed in more detail in the examples that follow.

[0122] Exemplary embodiments 1A illustrates an exemplary embodiment of a system 10 for in vivo or ex vivo monitoring of one or more analytes in a patient-user in accordance with the present technology. The system 10 includes one or more analyte sensor devices 100, which may be implanted within a patient-user, and a data processing system 150 in communication with the one or more analyte sensor devices 100. In some embodiments, the system 10 includes a receiver device 130 operable to receive wireless transmissions carrying data indicative of detected signals obtained from the one or more analyte sensor devices 100 and transmit and / or store the data in the data processing system 150. In some embodiments, the one or more analyte sensor devices 100 and / or receiver device 130 communicate with each other and with the data processing system 150 via a network of computers 140 accessible via the Internet (e.g., referred to as the cloud), and data from the one or more in vivo analyte sensor devices 100 and / or receiver device 130 may be transferred to the data processing system 150. Similarly, information from the data processing system 150 may be transferred to the receiver device 130 and / or one or more analyte sensor devices 100 .

[0123] The analyte sensor device 100 includes a sensor unit 110 and an electronic unit 120 secured within a housing or casing 101. The casing 101 is configured to protect the components of the sensor unit 110 and / or the electronic unit 120 from body fluids or substances when the in vivo analyte sensor device 100 is deployed inside a patient-user.

[0124] As shown in FIG. 1A , the one or more analyte sensor devices 100 include a first analyte sensor device 100Y deployed in a first portion of a patient-user's body, e.g., the head, torso, appendages, and other areas, which may or may not be coupled to an implant device deployed in the patient's body, e.g., an implant in the lungs, skull, neck, intestines, digestive track, etc., and the one or more analyte sensor devices 100 include a second analyte sensor device 100X deployed in a second portion of the patient-user's body, e.g., the tip, and may or may not be coupled to a second implant device, e.g., a knee implant device, etc.

[0125] In some example implementations, one or more analyte sensor devices 100 may be placed in direct communication with a fluid carrier, such as a blood vessel, and in some implementations, one or more analyte sensor devices 100 may be placed in the subcutaneous layer of the skin, for example, in the subcutaneous tissue above the muscle tissue and below the hair follicles.

[0126] In some embodiments, for example, one or more analyte sensors 100 are configured to detect both (i) a target analyte as a primary biomarker indicative of a health condition of the subject, and (ii) a secondary biomarker that is also indicative of a broader health condition of the subject and / or a specific health condition, such as an infection, that is detected simultaneously with the primary biomarker. Examples of secondary biomarkers include physiological parameters, such as temperature and / or vibration, in a body region in which the in vivo analyte sensor 100 is deployed within a patient-user. In such implementations, the physiological parameters may be detected based on signal analysis of the detected electrical signal by the electrochemical sensor electrodes.

[0127] In some exemplary embodiments, such as those discussed below in connection with FIG. 1B, the sensor unit 110 includes one or more electrochemical sensor electrodes, including at least two electrodes, i.e., a working electrode and a reference electrode, configured relative to the casing 101 such that a bodily fluid containing a target analyte can be exposed to the at least two electrodes of the sensor unit 110. For example, in some embodiments, the at least two electrodes of the sensor unit 110 are positioned on an outer surface of the casing 101, and other components of the sensing unit (e.g., electrically connected contacts, etc.) are disposed within the casing 101. The sensor unit 110 is electrically coupled to the electronic unit 120, e.g., via electrical interface contacts, to provide acquired electrical signals associated with the continuous monitoring of the target analyte by the electrochemical sensor electrode(s) to a signal conditioning unit and / or a wireless communication unit of the electronic unit 120, e.g., for subsequent data processing. Further details of the sensor unit 110 and electronic unit 120 for some embodiments of the in vivo analyte sensor device 100 are shown in FIG. 1B and other figures.

[0128] As shown in FIG. 1A, in some implementations, one or more in-vivo analyte sensor devices 100 wirelessly communicate acquired data directly to a receiver device 130. For example, one or more analyte sensor devices 100 may transfer data to the receiver device 130 using a low-power wireless communication protocol, such as Bluetooth Low Energy (BLE), Near Field Communication (NFC), low-frequency radio frequency (RF) signals in the range of 3 kHz to 1.3 MHz, or others. An exemplary embodiment of the receiver apparatus 130 includes a computing device 130A or a dedicated base station 130B. For example, the computing device 130A may include, but is not limited to, a smartphone, a tablet, a wearable computing device (e.g., a smart watch, smart glasses, or headgear, etc.), a laptop or desktop computer, or others. The dedicated base station 130B may include a data storage and / or data communication unit that facilitates communication of data from the one or more analyte sensor devices 100 to a data processing system 150 via Wi-Fi access or a cellular link to the network 140. In some implementations, for example, receiver device 130 may be embodied on multiple receiver devices, such as both computing device 130A (e.g., smartphone, tablet, etc.) and dedicated base station 130B, as shown in the example of Figure 1. In some implementations, for example, receiver device 130 may at least partially process received data for display on a display screen of receiver device 130 and / or for forwarding the received data to an external computer or computing system, such as data processing system 150. In some embodiments, for example, system 10 optionally includes software applications (apps) resident on receiver device 130 to control various data processing, storage, and communication functions for management of received data.

[0129] 1A may include one or more server computing devices 152, one or more client computing devices 154, and / or one or more databases 156 in data communication with each other. In an implementation, for example, computing device(s) 152, 154 and database(s) 156 communicate with each other and / or with other devices of system 10 via network 140. In some implementations, for example, data processing system 150 can remotely monitor data related to a patient-user acquired by one or more analyte sensor devices 100 and / or remotely operate aspects of system 10, such as, for example, modifying sensing parameters or protocols of one or more in vivo analyte sensor devices 100, data display or processing features of an app on receiver device 130, or others.

[0130] In some embodiments, for example, system 10 optionally includes a remote computing device 160 operated by a remote user to remotely monitor data associated with the patient-user acquired by one or more analyte sensor devices 100 that is forwarded to data processing system 150. For example, remote computer 160 may include a personal computer, such as a desktop or laptop computer, a mobile computing device, such as a smartphone, tablet, smartwatch, or other computing device. In some implementations, for example, remote computing device 160 is configured to receive only data that has been curated (e.g., selected, pre-processed, and / or formatted) by data processing system 150. In some implementations, for example, remote computing device 160 is configured to operate one or more aspects (e.g., functions) of system 10 remotely. For example, remote computing device 160 may implement a remote user software application (remote user app) configured to provide such display, storage, and / or management capabilities to the remote user. Remote users may include, for example, healthcare providers (HCPs), such as doctors, nurses, family members or other caregivers of the patient user, or health insurance payers or other types of stakeholder entities or individuals with respect to the patient user's health.

[0131] FIG. 1B is a block diagram illustrating an exemplary embodiment of the analyte sensor 100 shown in FIG. 1A, which is shown in FIG. 1B as analyte sensor 100B. In FIG. 1B, analyte sensor 1B 100B includes an exemplary embodiment of a sensor unit 110 (shown as sensor unit 110B) and an exemplary embodiment of an electronic unit 120 (shown as electronic unit 120B). Sensor unit 100B of analyte sensor 110B includes a substrate 111, a plurality of electrodes 113 disposed on substrate 111, an electrical interface 115 including a plurality of electrical contact sites (e.g., pads, pins, etc.), and a plurality of interconnects 117 disposed on substrate 111 and configured to couple electrodes 113 to respective contact sites of electrical interface 115. In some embodiments, for example, at least a portion of the plurality of electrodes 113 are configured as electrochemical sensor electrodes for detecting an electrical signal corresponding to a reaction involving a target analyte in a fluid exposed to electrodes 113. In some embodiments, for example, the plurality of electrodes 113 includes a pattern of electrodes including at least one working electrode 113W and at least one reference electrode 113R, eg, without a counter electrode associated with the sensor.

[0132] In various embodiments, for example, the substrate 111 can be configured as a wafer-based substrate that is rigid, electrically insulating, and includes a semiconductor material, such as a crystalline silicon material or an amorphous (non-crystalline) silicon material. The wafer-based substrate can be configured with a particular size and / or geometric shape such that one or more electrode patterns can be fabricated on a single wafer. In some embodiments of the substrate 111, for example, the wafer-based substrate includes silicon oxide (e.g., silica, glass, or others), germanium (e.g., undoped or doped), gallium arsenide, or others.

[0133] In various embodiments, for example, at least one reference electrode 113R includes iridium (e.g., iridium oxide) and at least one working electrode 113W includes iridium and / or platinum (e.g., 90 / 10 platinum / iridium). For example, in an embodiment of the sensor unit 110 where at least one reference electrode 113R includes iridium (e.g., an iridium oxide surface of the reference electrode), the iridium-based reference electrode can provide longevity, stability, and protection to the analyte sensor device 100 for detecting target analytes. In implementations, for example, the iridium-based reference electrode is resistant to electrode damage from reactive species in the fluid (e.g., hydrogen peroxide), which derails and eventually destroys conventional Ag / AgCl reference electrodes. This resistance to breakdown provides the sensor unit 110 with several advantages over conventional electrochemical sensors, including, for example, prevention of substantial sensor drift, thus mitigating the need for recalibration of the sensor unit 110 and increasing the use (lifespan) of the sensor unit 110 in a single in vivo deployment, for up to one year or more. Additionally, implementation of the sensor unit 110 with an iridium-based reference electrode allows for a lower operating voltage potential across the working reference electrode, for example, in the range of 100 mV to 200 mV, thereby allowing for reduced power consumption of the overall sensor device (e.g., further mitigating battery replacement or charging concerns) and allowing embodiments of the in vivo analyte sensor 100 to be smaller in size or optimally shaped (e.g., because smaller batteries may be used). Additionally, the lower operating voltage potential across the electrodes prevents the sensor unit 110 from suffering from signal interference from other components in the fluid, for example, caused by secondary chemical effects on analyte sensing. Examples of such interfering components include, but are not limited to, dopamine, aspirin, acetaminophen, or others.

[0134] In some embodiments, for example, the at least one working electrode 113W can be functionalized with a chemical layer 119 to interact with a target analyte to promote a reaction resulting in a change in charge potential and / or flow at or near the at least one working electrode 113W, such that an electrical signal associated with the reaction is detectable at the at least one working electrode 113W relative to the at least one reference electrode 113R for measuring a parameter associated with the target analyte. In some embodiments, the chemical layer 119 can include a membrane configured to provide a restricted area to control the flux of the target analyte and / or other analytes or reactive species in a bodily fluid exposed to the membrane-coated at least one working electrode 113W.

[0135] An example of a membrane as the chemical layer 119 includes a multi-layer membrane including an outer layer exposed to bodily fluids that regulates permeation of reactive species, and an inner layer bonded between the outer layer and the surface of at least one working electrode 113W to immobilize a catalyst (e.g., an enzyme, a mediator, etc.) to promote a reaction with the permeating reactive species for detection of a target analyte. For example, to implement in vivo glucose monitoring using a peroxide-based glucose sensor, the chemical layer 119 can include glucose oxidase (GOx) entrapped in the inner layer of the exemplary membrane, which reacts with glucose (CH 12 The glucose and oxygen react in the presence of the catalyst GOx to produce gluconic acid (CH), such that gluconic acid (CH) and oxygen (O) permeate through the outer layer of the membrane. 12 O7) and hydrogen peroxide (H2O2) (and / or gluconolactone (C6H 10 and forming hydrogen peroxide (H2O6) and H2O2 in a reaction that also includes water (H2O), where the hydrogen peroxide product dissociates into oxygen and charge carriers (hydrogen cations and electrons) to generate a signal current that is measured proportional to the glucose in the reaction. Examples of multilayer membranes include those described in U.S. Patent Publication No. 2021 / 096157A1, entitled "Chemically Fused Membrane for Analyte Sensing," which is incorporated herein by reference.

[0136] 1B, the electronic unit 100B of the analyte sensor device 120B includes a signal conditioning unit 123, a power source 129, a wireless communication unit 127, and an electrical interface 125, which may include conductive contact sites (e.g., pads, pins, or other contact configurations) that electrically couple with the electrical interface 115 of the sensor unit 110B. The electronic unit 120B is configured to receive and at least partially process electrical signals acquired from one or more electrochemical sensor electrodes of the sensor unit 110B. For example, the electrical signals are received at corresponding contact sites of the electrical interface 125 (via the electrical interface 115) and provided to the signal conditioning unit 123 to improve the quality of the electrical signals acquired from the sensor unit 110B. In such an implementation, the output of the signal conditioning unit 123 may include data associated with the signal-processed electrical signals that are wirelessly transmitted by the wireless communication unit 127 to an external device. In an exemplary embodiment of the electronic unit 120B, the power source 129 may include a battery, a fuel cell, or other power source for powering components of the electronic unit 120B and / or the sensor unit 110B.

[0137] In some embodiments, for example, the signal conditioning unit 123 may include circuitry including one or more filters and / or one or more amplifiers to enhance the raw electrical signals detected by the at least two electrodes of the sensor unit 110B to increase the signal-to-noise ratio (SNR) of the electrical signals, thereby generating data including signal-processed electrical signals. In some embodiments, the signal conditioning unit 123 may include drive circuitry for generating operating electrical signals that generate potentials and / or currents at the electrochemical sensor electrode content(s) of the sensor unit 110B to operate electrochemical detection techniques implemented at the electrode(s) in an embodiment of the analyte sensor 100B to detect a target analyte.

[0138] In some embodiments, the wireless communication unit 127 includes a wireless transmitter, receiver, and / or transceiver device including an antenna that can communicate with an external device to communicate raw, partially processed, or fully processed data from the signal conditioning unit 123 (and / or the data processing unit 121 discussed below). For example, the wireless communication unit 127 can be configured to manage a communication protocol for transmission or reception via the antenna. An exemplary transceiver unit can include a BLE chipset for communicating with BLE-enabled devices, e.g., smartphones, tablets, or other external computing devices, such as the receiver device 130.

[0139] In some embodiments, the electronic unit 120B optionally includes a data processing unit 12110B that at least partially processes the conditioned electrical signal to (i) generate data, e.g., in analog or digital form, and / or (ii) control the functionality of the electronic unit 120B and / or the sensor unit 110B. For example, the data processing unit 121 may be configured to manage data acquisition on data channels associated with electrodes of the sensor unit 110B. In some embodiments of the data processing unit 121, for example, the data processing unit 121 may include a processor 121A for processing data and a memory 121B in communication with the processor 121A for storing and / or buffering data. In various embodiments, for example, the processor 121A may include one or more processors and the memory 121B may include one or more memory units. For example, the processor 121A may include a central processing unit (CPU), a microcontroller unit (MCU), a graphics processing unit (GPU), or other type of processor. For example, memory 121B may include and store processor-executable code that, when executed by the processor, configures data-processing unit 121 to perform various operations, such as receiving information, commands, and / or data, processing information and data, and transmitting or providing information / data to another device. To support various functions of data-processing unit 121, memory 121B may store information and data, such as instructions, software, values, images, and other data that is processed or referenced by processor 121A. For example, various types of random access memory (RAM) devices, read-only memory (ROM) devices, flash memory devices, and other suitable storage media may be used to implement the storage functionality of memory 121B.In some embodiments, the data processing unit 121 includes an input / output (I / O) unit 121C for interfacing the processor 121A and / or the memory 121B to other modules, units, or devices associated with external devices, such as, for example, the receiver device 130, the data processing system 150, the remote computing device 160, and / or other external devices. In some embodiments, the processor 121A, the memory 121B, and / or the I / O unit 121C communicate with a wireless communication unit 127, such as, for example, a transmitter (Tx) or a transmitter / receiver (Tx / Rx) unit. For example, in such an embodiment, the I / O unit 121C can interface the processor 121A and the memory 121B with the wireless communication unit 127 to utilize various types of wireless interfaces, for example, compatible with typical data communication standards, that may be used for communication between the data processing unit 121 and other devices. Data communication standards include, but are not limited to, Bluetooth, Bluetooth Low Energy (BLE), Zigbee, IEEE 802.11, Wireless Local Area Network (WLAN), Wireless Personal Area Network (WPAN), Wireless Wide Area Network (WWAN), WiMAX, IEEE 802.16 (Worldwide Microwave Access Interoperability (WiMAX)), 3G / 4G / LTE / 5G / 6G cellular communication methods, and parallel interfaces. In some implementations, the data processing unit 121 can interface with other devices using a wired connection via the I / O unit 121C. The data processing unit 120B can also interface with other external interfaces, data storage sources, and / or visual or audio display devices, etc. to obtain and transfer data and information that can be processed by the processor 121A, stored in the memory 121B, or presented on an output unit of the receiver device 130 (e.g., smartphone, tablet, etc.) or other external device to the analyte sensor device 100.

[0140] In some exemplary embodiments of the analyte sensor device 100B, the analyte sensor device 100B includes two electrochemical sensor electrodes, with at least two electrodes (i.e., a working electrode and a reference electrode) of each respective electrochemical sensor electrode disposed on an exterior surface of the casing 101, e.g., a top wall, a bottom wall, or a side wall. In some embodiments, for example, the exterior surface of the casing 101 that positions the at least two electrodes of each respective electrochemical sensor electrode may include a wall within a hollow region of the casing 101. In various embodiments, for example, the body or form of the example analyte sensor device 100B may have a rectangular shape, however, in other examples, the example analyte sensor device 100B may be configured to have a variety of other shapes, including a curved exterior wall of the casing 101, and / or a cylindrical, conical, elliptical, pyramidal, trapezoidal, or non-uniform shape. In some embodiments, the casing 101 may include a non-permeable material that is rigid or flexible.

[0141] In some embodiments, for example, the casing 101 may include one or more coatings. For example, the coating may include a non-permeable material, a material to hermetically seal the electrical interconnection components (e.g., electrical interface 115 and interconnect 117) disposed on the substrate 111 to cover the electrical interconnection components and provide an electrical shield from bodily fluids, or other material. Examples of coatings of non-permeable material(s) include, but are not limited to, parylene, urethane, silicone, or polytetrafluoroethylene (e.g., Teflon) materials. These coatings may extend the life of the sensor by mitigating (i.e., reducing) biodegradation, and in some cases provide a carrier for a biodegradation inhibitor to extend function over time and / or provide electroelasticity. Examples of biodegradation inhibitors provided by the coating may include rapamycin, everolimus, or others. Biodegradation can cause functional changes in the performance of the sensor, an example being sensor drift.

[0142] Sensor drift, also simply called drift, occurs when the signal output of an electrochemical sensor loses sensitivity in detecting a target analyte, usually due to the destruction of materials at the working and reference electrodes of the sensor. Drift is the amount of change that the signal output undergoes over time. Typically, conventional sensors can mitigate sensor drift by calibration, for example, by first calibrating and recalibrating the electrochemical sensor over a limited lifespan. Sensor drift can be due to small and non-deterministic temporal variations of the sensor, which can plague the sensor's ability to accurately measure non-significant events, such as gradual changes in temperature.

[0143] Biodegradation of the sensor leading to sensor drift can be observed as a change in current or voltage output signal, for example, due to an actual change in resistance at the sensor electrode. Biodegradation can also affect the membrane to facilitate the electrochemical reaction(s) for analyte detection by increasing the impedance to the permeability of the analyte to reach the chemical reaction zone to the consistency of electrode signal generation, and / or by increasing impurity bioproducts that can penetrate the permeable membrane and result in base electrode degradation. Exemplary coating materials can enhance the stability and support the lifetime of the sensor's performance duration. For example, biodegradation inhibitors present in the coating allow the membrane to be free of biofouling and ensure that the permeability of the membrane's matrix does not clog.

[0144] FIG. 1C is a block diagram illustrating an exemplary embodiment of a sensor unit 110 for an analyte sensor, shown in FIG. 1C as sensor unit 11C. Similar to the example of sensor unit 11B shown in FIG. 1B, sensor unit 110C includes a wafer-based substrate 111C, a plurality of electrodes disposed on substrate 111C, an electrical interface 115c consisting of a plurality of electrical contact sites (e.g., pads, pins, etc.), and a plurality of interconnects 117C disposed on substrate 111C and configured to couple the electrodes to respective contact sites of electrical interface 115C. In some embodiments, substrate 111C includes a wafer-based substrate, and in some embodiments, for example, at least a portion of the plurality of electrodes is configured as an electrochemical sensor electrode for detecting an electrical signal corresponding to a reaction involving a target analyte in a fluid exposed to the electrodes. In some embodiments, for example, the plurality of electrodes is configured as a two-electrode sensor electrode, including at least one working electrode 113W and at least one reference electrode 113R, for example, without a counter electrode associated with the sensor electrode. In other embodiments (FIG. 1C), for example, the plurality of electrodes are configured as a three-electrode sensor including at least one working electrode 113W, at least one reference electrode 113R, and at least one counter electrode (not shown). In various embodiments, for example, at least one reference electrode 113R optionally includes iridium (e.g., iridium oxide). In various embodiments, for example, at least one working electrode 113W optionally includes iridium and / or platinum (e.g., 90 / 10 platinum / iridium). In some embodiments, for example, the at least one working electrode 113W is functionalized with the chemical layer 119 to facilitate a reaction that interacts with the target analyte to result in a change in charge potential and / or flow at or proximate to the surface of the at least one working electrode 113W, and an electrical signal related to the reaction is detectable at the at least one working electrode 113W relative to the at least one reference electrode 113R, and an electrical signal related to the reaction is detectable relative to the at least one reference electrode 113R to measure a parameter related to the target analyte.In some embodiments, the chemical layer 119 of the sensor unit 110C may include a membrane such as the multilayer membrane described in U.S. Patent Publication No. 2021 / 096157A1, entitled "Chemically Fused Membrane for Analyte Sensing," which is incorporated herein by reference. Thus, in one embodiment, the present disclosure provides a sensor device having an iridium electrode and a multilayer membrane, optionally having other features described herein. Exemplary implementations of the sensor unit 110C may include any of the features and attributes of the sensor unit 110B described above.

[0145] In one embodiment, the sensor device has a two-electrode temporary consisting of a working electrode and a reference electrode, optionally in sterile form. For clarity, a two-electrode dielectric, or a two-electrode dielectric, has not one electrode, not three electrodes, but three or fewer electrodes. In one embodiment, the working electrode includes a surface layer containing glucose oxidase, which is reactive with glucose present in the body fluid to which the two-electrode temporary is exposed. Underlying the layer of glucose oxidase is a layer of platinum, in one embodiment pure platinum, i.e. platinum consisting of at least 95% by weight (wt%) platinum, or at least 96% by weight, or at least 97% by weight, or at least 98% by weight, or at least 99% by weight platinum, based on the weight of the metal present in the layer. Underlying the platinum layer is a layer of titanium, in one embodiment formed of pure titanium, i.e. titanium consisting of at least 95% by weight (wt%) titanium, or at least 96% by weight, or at least 97% by weight, or at least 98% by weight, or at least 99% by weight titanium metal, based on the total metal present in the layer. Thus, in one embodiment, the working electrode is located on top of the silicon oxide substrate in a sandwich format, where the titanium layer is on top of and directly adjacent to the silicon oxide substrate, the platinum layer is on top of and directly adjacent to the titanium layer, and the oxidized glucose-containing layer is on top of and directly adjacent to the platinum layer. In one embodiment, the reference electrode includes a surface layer including iridium oxide that is exposed to a glucose-containing fluid detected by the working electrode. Underlying the iridium oxide is a layer of iridium metal, operatively pure iridium metal, i.e., iridium consisting of at least 95% by weight (wt%) iridium metal, or at least 96% by weight, or at least 97% by weight, or at least 98% by weight, or at least 99% by weight iridium metal, based on the weight of the metal present in the layer. Underlying the layer of iridium metal is a layer of platinum metal, optionally pure platinum metal, i.e., platinum consisting of at least 95% by weight (wt%) platinum, or at least 96% by weight, or at least 97% by weight, or at least 98% by weight, or at least 99% by weight platinum, based on the weight of the metal present in the layer.Optionally, the platinum layer is, for example, equivalent to the same composition as the platinum layer of the working electrode. Underlying the platinum layer in the reference electrode is a layer of titanium, optionally consisting of pure titanium, i.e., at least 95% by weight (wt%) titanium, or at least 96% by weight, or at least 97% by weight, or at least 98% by weight, or at least 99% by weight titanium metal, based on the total metals present in the layer. Optionally, the platinum layer in the reference electrode is, for example, equivalent to the same composition as the titanium layer present in the working electrode. Thus, in one embodiment, the reference electrode is located on top of a silicon oxide substrate in a sandwich format, where the titanium layer is directly adjacent to the silicon oxide substrate, the platinum layer is directly adjacent to the titanium layer, the iridium metal layer is on top of and directly adjacent to the platinum metal layer, and the iridium oxide layer is on top of and directly adjacent to the iridium metal layer. The working electrode may be described as including or consisting of three layers: a titanium metal layer, a platinum metal layer, and a layer containing glucose oxidase. The reference electrode may be described as including or consisting of four layers: a titanium metal layer, a platinum metal layer, an iridium metal layer, and an iridium oxide layer. Optionally, the titanium metal layer of the working electrode is of the same composition as the titanium metal layer of the reference electrode, and optionally, the titanium metal layer of the working electrode is of the same thickness as the titanium metal layer of the reference electrode. Optionally, the platinum metal layer of the working electrode is of the same composition as the platinum metal layer of the reference electrode, and optionally, the platinum metal layer of the working electrode is of the same thickness as the platinum metal layer of the reference electrode.

[0146] Optionally, the surface area of ​​the top surface of the reference electrode is greater than the surface area of ​​the top surface of the working electrode. In one embodiment, the top surface of the working electrode has a shape selected from a circle and a square, where the top surface has a diameter (for a circle) or a width (for a square, the width may also be referred to as the length) in addition to a center point. In one embodiment, the top surface of the reference electrode has a shape selected from a circle and a square, where the top surface has a diameter (for a circle) or a width (for a square, the width may also be referred to as the length) in addition to a center point. For convenience, the diameter or width of the electrode will be referred to simply as the width, even though the electrode may have a circular shape.

[0147] The two electrodes may be located on a non-conductive substrate, such as silicon dioxide (SiO2), and the non-conductive substrate may be in a wafer (planar) form, as opposed to a tubular form, for example. In one embodiment, the non-conductive substrate is present in a non-planar form.

[0148] In one embodiment, the working electrode and the reference electrode are located on a surface of the substrate and are separated from each other by a distance, the distance being the separation between the center point of the reference electrode and the center point of the working electrode. In one embodiment, the distance between these two points is less than four times the width of the larger of the working and reference electrodes, and in one embodiment, the reference electrode has a larger width than the working electrode.

[0149] In one embodiment, the present disclosure provides a sensor device wherein a substrate is a wafer comprising silicon dioxide, the working electrode comprises a layer of titanium metal in direct contact with the substrate, a layer of platinum metal in direct contact with the layer of titanium metal, and a chemical layer in direct contact with the layer of platinum metal, the chemical layer comprising glucose oxidase configured to promote a reaction involving glucose that generates an electrical signal at the electrochemical sensor electrode, and a reference electrode comprises a layer of titanium metal in direct contact with the substrate, a layer of platinum metal in direct contact with the layer of titanium metal, a layer of iridium metal in direct contact with the layer of titanium metal, and a layer of iridium oxide in direct contact with the layer of iridium metal oxide. In embodiments, each of the mentioned titanium metal, platinum metal, and iridium metal layers contains at least 95% by weight of the mentioned metal, or at least 96% by weight of the mentioned metal, or at least 97% by weight of the mentioned metal, or at least 98% by weight of the mentioned metal, or at least 99% by weight of the mentioned metal, each weight percent value being based on the total weight of the metal in the mentioned layer. For example, in one embodiment, the titanium metal layer contains at least 99% by weight of titanium metal, the platinum metal layer contains at least 99% by weight of platinum metal, and the iridium metal layer contains at least 99% by weight of iridium, based on the weight of the metal in each named layer.

[0150] In some implementations of the sensor unit 110C, for example, the sensor unit 110C may be integrated or incorporated into a wearable sensor device used in a sensor system, where the sensor electrodes of the wearable sensor device are inserted into the patient's body. One example of a sensor system in which the sensor unit 110C may be integrated or incorporated includes an embodiment of a transdermal analyte sensor system described in U.S. Patent No. 8,615,282 B2, entitled "Analyte Sensor," which is incorporated herein. Another example of a sensor system in which the sensor unit 110C may be integrated or incorporated includes an embodiment of a telemetered characteristic monitor system, including a transdermal sensor set, in U.S. Patent No. 6,809,653 B1, entitled "Telemetered Characteristic Monitor System and Method of Use," which is incorporated herein by reference. Another example of a sensor system in which the sensor unit 110C may be integrated or incorporated includes an embodiment of an analyte monitoring system described in U.S. Patent No. 7,920,907 B2, entitled "Analyte Monitoring System and Method," which is incorporated herein by reference.

[0151] In one embodiment, the sensor device of the present disclosure is sterilized. In particular, if the sensor device is intended for in vivo placement, in one embodiment, the sensor device is sterilized. In one embodiment, at least the temporary material of the electrode is sterilized. If the electrode temporary includes a functional enzyme, for example, an enzyme that should be glucose oxidase if the electrode assists in the detection and measurement of the presence and / or concentration of glucose in a bodily fluid, the electrode temporary, and optionally components associated with the electrode temporary, may also be sterilized. In one embodiment, sterilization is achieved by e-beam sterilization. Optionally, sterilization is achieved using low-temperature e-beam sterilization, i.e., e-beam sterilization performed on the temporary electrode at a low temperature, such as below room temperature, e.g., below 25°C, to maintain the activity of the immobilized enzyme.

[0152] FIG. 2A illustrates a top view of an exemplary embodiment of a sensor unit 110 of an analyte sensor device 100 having a two-electrode content, shown as a sensor unit 210. The sensor unit 210 includes a sensor carrier system 201 and a temporary set of electrochemical sensor electrodes 212 that can be reversibly coupled to and electrically interfaced with the sensor carrier system 201. The sensor carrier system 201 is operable to electrically connect to the electronic unit 120 of the analyte sensor device 100 via an electrical interface component 225 (e.g., a wire, pin, or other conductive structure). In some embodiments, for example, the electrical interface component 225 can extend from the sensor unit 210 to contact a conductive contact site of the electronic unit 120. Also, in some embodiments (not shown), the electrical interface component of the electronic unit 120 can extend from the electronic unit 120 to contact, for example, a conductive contact site of the sensor unit 210 in the sensor carrier system 201.

[0153] The electrochemical sensor electrode content 212 of the exemplary sensor unit 210 shown in FIG. 2A includes a two-electrode temporary material consisting of a working electrode 213W and a reference electrode 213R, which are disposed on an electrically insulating wafer-based substrate 211 of the electrochemical sensor electrode content 212. In some embodiments of the sensor unit 210, for example, the working electrode 213W may include platinum, iridium, gold, silver, titanium, single-walled or multi-walled carbon nanotubes, and / or another conductive material or combinations thereof. In some embodiments of the sensor unit 210, for example, the reference electrode 213R may include iridium (e.g., iridium oxide, or iridium oxide / iridium oxide).

[0154] In an exemplary embodiment of the reference electrode 213R of the sensor unit 210 including iridium, the iridium oxide maintains a constant reference to balance the detectable signal, so the iridium-based reference electrode can provide a longevity to the analyte sensor device 100, whereas silver oxide electrodes are typically damaged over time by the potential applied to the reference electrode (e.g., typically 300-350 mV), limiting their practical use to less than 30 days. In contrast, the exemplary iridium oxide reference electrode allows the analyte sensor device 100 to operate at lower power (e.g., a potential of about 150 mV applied to the iridium-based reference electrode, with an output current in the range of about 10 nA-25 nA, compared to measurements of 600 mV or more for conventional platinum electrodes), thereby allowing the sensor to be used for a year or more. Additionally, the iridium-based reference electrode may also enable the sensor system to function at lower voltage potentials, i.e., substantially less than 500 mV, e.g., in the range of 100 mV to 200 mV, thereby preventing interference from secondary chemicals, such as dopamine, sweat acetaminophen, a numbing chemical used in the medical treatment of pain, and others, that may also be present in the body environment monitored by the in vivo or ex vivo sensor device of the present disclosure, due to operating at a lower potential difference across the working electrode and the (iridium-based) reference electrode.

[0155] In an implementation, the two electrodes of the bipolar sensor cooperate with each other to balance the measurable signal from noise of the biological system being detected by the sensor unit 210, such as intrinsic biological noise caused by cellular or biomolecular interactions and processes, or extrinsic noise caused by electronic systems inside or outside the patient's body, such as peripheral electronic devices (cell phones, etc.) or other medical equipment. In various exemplary embodiments of the sensor unit 210, the extra 212 electrochemical sensor electrodes advantageously allow the sensor device 100 to have a substantially smaller footprint and be more reliable for signal processing, as compared to, for example, some conventional electrochemical sensors having three or more electrodes.

[0156] The two-electrode sensor interim can also provide enhanced gating / response detection for stable or unstable environmental aspects for signal processing. Additionally, area / relationship factors can be important to the operability of a two-electrode electrochemical sensor. For example, the ratio of working electrode area and reference electrode area is such that the working electrode has a smaller area and the reference electrode has a larger area. The potential difference (e.g., potential voltage between two similar or different electrode material surfaces) also factors into the electrode area and affects the functional life to the overall signal performance. The present design of the exemplary two-electrode interim for various embodiments of the electrochemical sensor electrode interim 212 allows for two-electrode designs with exemplary ratios of minimum area (working electrode) to maximum area (reference electrode), including ratios of 1:15, or 1:10, or 1:5, or 1:4, or even smaller, based on the sensor life for functional detection intended by the design. An exemplary distance separating the working electrode 213W and the reference electrode 213R can be 1 μm (1 micron) or more. For the exemplary electrodes of the sensor unit 210, or other exemplary embodiments of a sensor unit according to the disclosed technology, the working electrode(s) and reference electrode(s) may be configured to have the areas shown in Table 1. Note that the size, shape, and surface area configuration of the electrodes are not limited to those shown in Table 1.

[0157] [Table 1]

[0158] For example, an electrochemical sensor electrode temporary 212 having two electrodes is operable to detect changes in environmental conditions (e.g., temperature) of a body region (zone) in which the sensor unit 210 is deployed, while a reference electrode 213R comprising iridium oxide and a working electrode 213W (e.g., comprising iridium) detect a parameter (e.g., concentration) of a target analyte (e.g., glucose, oxygen, etc.). The platinum working and iridium based reference two electrodes of the electrochemical sensor electrode temporary 212 detect the analyte parameter (e.g., glucose concentration) and the environmental condition (e.g., temperature in the local environment of the sensor unit 210) in part due to electrode signal drift (i.e., signal bias of a stable iridium reference or counter electrode), while a significant signal change detected across the working electrode 213W and reference electrode 213R is due to a parameter change related to the target analyte, while a subtle signal change detected across the two electrodes is due to a change in an environmental factor affecting the electrodes, e.g., temperature increase, etc. For example, a two-electrode electrochemical sensor electrode's temporary 212 without a counter electrode is configured to be sensitive to such changes in the environment, such as temperature, that would cause a swing in the (otherwise stable) bias measurement for the analyte (e.g., glucose measurement). On the other hand, for a different configuration of electrochemical sensor electrode's temporary 212 having a three-electrode temporary, for example, the counter electrode may impede the ability to measure changes in the bias of the measured electrical signal between the working and reference electrodes that may be associated with such environmental changes, because the change in the bias signal is immediately accommodated at the working electrode by the counter electrode.

[0159] In some embodiments of the sensor unit 210, for example, the wafer-based substrate 211 comprises silicon oxide (e.g., silica, glass, or other), germanium (e.g., undoped or doped), gallium arsenide, or other. The wafer-based substrate 211 can provide several advantages to the in vivo or ex vivo sensor device 100 in terms of operation, preparation, and / or manufacturing. For example, the wafer-based substrate 211 can allow the end user to modify the three-dimensional shape of the electrodes and / or chemically modify (e.g., passivate) the substrate to facilitate, for example, the adaptation of membranes used for electrochemical sensing from a top-to-bottom approach. This allows for structural uniqueness of the sensor device from the surface construction point as it relates to top-to-bottom material layering on the substrate and electronics / communications integration. This also allows for the fabrication of connections to processing components for specific mechanical and configurational structures, allowing for, for example, size and / or morphology changes. Importantly, for example, the wafer-based substrate 211 allows the ability to create surface roughness on the sensor device to promote extended analyte sensing lifespan, e.g., the surface roughness (1) allows for an RMS (root mean square) configuration that can be measured in a peak-peak or peak-valley manner and increases the surface area in a 3D cross-sectional aspect, e.g., allows for an enlarged signal generating surface while maintaining the same perimeter for the chemical oxidase reaction, as compared to a 2D cross-sectional aspect. In some implementations of the analyte sensor of the present disclosure, the wafer-based substrate may or may not maintain, e.g., silica, germanium, or other initial base substrate material, such that the base substrate layer can act as a scaffold for surface support as other material layers are compiled onto the base substrate layer. In some examples, a polymer layer may be applied as the first layer on the base substrate, but the polymer layer (first layer) may be lifted from the initial base layer, even silica or other material layer(s), which may result in the production of an electrode sensor with minimal stiffness compared to the initial layer properties.For example, this aspect of the wafer-based substrate can provide a more connected and flexible layer based on the first polymer layer properties, allowing for more optimal handling and mechanical properties when delivered and implanted at the selected host location.

[0160] The electrochemical sensor electrodes 212 include conductive contact sites 215 and interconnect wires 217 disposed on or in the wafer-based substrate 211 and configured to couple to the electrodes 213W, 213R. In some embodiments of the sensor unit 210, for example, the conductive contact sites 215 and / or interconnect wires 217 may include platinum, gold, iridium, etc. In an exemplary implementation of the electrochemical sensor electrodes, the substrate 211 may be fabricated layer-by-layer and mask-by-mask, as described above, which allows the entire sensor substrate to be built up (i) interconnected layer-by-layer, or (ii) in a disconnected manner (selected by design), with only certain locations being connected from the electrodes to the electronics unit (e.g., control unit, signal processing circuitry, and / or power supply). This may allow for more compact sizing and overall faster processing for signal transfer.

[0161] In the embodiment shown in Figure 2A, the sensor carrier system 201 of the sensor unit 210 includes contact site 205A connected to contact site 205B via respective interconnects 207 disposed on or in an electrically insulating substrate 202. Contact site 205A is disposed on the substrate 202 to electrically interface with contact site 215 of the electrochemical sensor electrode attachment 212, and contact site 205B is disposed on the substrate 202 to electrically interface with electrical interface component 225, thereby electrically connecting the electrochemical sensor electrode attachment 212 with the electronics unit 120. It should be noted that the top view illustrates contact site 215 (of the electrochemical sensor electrode attachment 212) and contact site 205A (of the sensor carrier system 201) as spatially separated, and this is done for illustrative purposes. It should be appreciated that the contact sites 215 are located on the attachment side of the temporary 212 electrochemical sensor electrodes, and the contact sites 205A are positioned on the substrate 202 such that they are aligned with the corresponding contact sites 215 when the temporary 212 electrochemical sensor electrodes are coupled to the sensor carrier system 201 of the sensor unit 210. In various implementations, for example, certain components of the sensor unit 210 (e.g., the contact sites 205, the interconnects 207, the substrate 202, etc.) are contained within the sensor carrier system 201 and are protected from exposure to external agents when the analyte sensor device 100 is deployed in vivo.

[0162] In some embodiments of the sensor unit 210, the working electrode 213W may include an embodiment of the chemical layer 119 for monitoring the target analyte by the sensor unit 210. In some implementations, for example, the analyte sensor device 100 may be configured to detect glucose, oxygen, ketones, and / or other analytes that may be measured by the sensor unit 210, and the electronic unit 120 transmits data representative of the detected electrical signals, which are then linked to the data processing system 150 (including, for example, uploading to the database 156) for analysis and continuous functional monitoring for evaluation of the subject's health status. For example, the data processing system 150 may apply analysis and control methods related to the user's health status and behavior related to foods, vitamins, fluids, or prescribed medications, or other, to baseline models, such as Clarke Error grids or equivalent models. In some embodiments, for example, the analyte sensor device 100 is configured to detect electrical signals from working and reference electrodes based on an engineered membrane (such as, for example, membrane 419 discussed later in FIG. 4) designed for analyte specificity directed to glucose, oxygen, and ketones.

[0163] In some embodiments of the sensor unit 210, for example, the sensor unit 210 includes additional interconnecting electronic components that can facilitate interconnectivity of multiple electrochemical sensor electrodes and coupling to the sensor carrier system 201. An example embodiment of a multi-electrochemical sensor assembly for the sensor unit 210 is described below in FIG. 2C.

[0164] FIG. 2B is a diagram showing a top view of an exemplary embodiment of a sensor unit 110 of an analyte sensor device 100 having a three-electrode content disposed on an electrochemical sensor electrode content 212B, the exemplary embodiment of the sensor unit 110 shown in FIG. 2B is illustrated as sensor unit 210B. The electrochemical sensor electrode content 212B of the exemplary sensor unit 210B shown in FIG. 2B includes a three-electrode content consisting of an embodiment of a working electrode 213W, an embodiment of a reference electrode 213R, and a counter electrode 213C, which are disposed on an embodiment of an electrically insulating, wafer-based substrate 211. In some implementations, for example, the counter electrode 213C may be used as a development tool and / or to condense a reference signal balance to the working electrode, such as a test mode for a particular application of the sensor unit 210B. There may be other instances involving detection development where a counter electrode is preferred as an ad-hoc component of the electrochemical sensor electrode. Also, with regard to the exemplary illustration of FIG. 2B, it will be understood that, similar to FIG. 2A, the contact site 215 is disposed on the mounting side of the electrochemical sensor electrode content 212, and the contact site 205A is disposed on the substrate 202 so as to align with the corresponding contact site 215 when the electrochemical sensor electrode content 212B is coupled to the sensor carrier system 201B of the sensor unit 210B.

[0165] 2C is a top view of an exemplary embodiment of a sensor unit 110 of an analyte sensor device 100 having a plurality of two-electrode contents, shown as sensor unit 210C in FIG. 2C. In such an embodiment, for example, the sensor unit 210CC includes a plurality of sets of contact sites 205A, contact sites 205B, and interconnects 207 to electrically interface with a plurality of electrochemical sensor electrode contents, such as the electrochemical sensor electrode content 212 and the second electrochemical sensor electrode content 214 shown in the example of FIG. 2C. In this example, the second electrochemical sensor electrode continuum 214 is configured to have the same or similar structure as the electrochemical sensor electrode continuum 212; however, in some embodiments, the working electrode 213W of the second electrochemical sensor electrode continuum 214 may be modified with a different chemical layer 119 than the chemical layer 119 on the working electrode 213W of the electrochemical sensor electrode continuum 212 to sense a different target analyte when the sensor 210C is deployed and operated in vivo. In some embodiments, for example, multiple electrochemical sensor electrode contents can share the same substrate, while in some exemplary embodiments, such as shown in Fig. 2C, multiple electrochemical sensor electrode contents can be configured on separate substrates. Also, for the exemplary view of Fig. 2C, similar to Fig. 2A, it is understood that the contact site 215 is disposed on the attachment side of the electrochemical sensor electrode string 212 and the second electrochemical sensor electrode string 214, and the contact site 205A is disposed on the substrate 202 so as to be aligned with the corresponding contact site 215 when the electrochemical sensor electrode string 212 and the second electrochemical sensor electrode string 214 are coupled to the sensor carrier system 201C of the sensor unit 210C.

[0166] 3 shows a diagram of another exemplary embodiment of the sensor unit 110 of the analyte sensor device 100 having a two-electrode electrochemical sensor electrode temporary and an electrical conductivity sensor, shown in FIG. 3 as sensor unit 310. The sensor unit 310 includes at least one two-electrode temporary disposed on an electrically insulating wafer-based substrate 311. In the example shown in FIG. 3, the sensor unit 310 includes a first electrode temporary including a first working electrode 313W-1 and a first reference electrode 313R-1, and a second electrode temporary including a second working electrode 313W-2 and a second reference electrode 313R-2. The wafer-based substrate 311 can be configured to a particular size such that multiple sensor units 310 can be fabricated on a single wafer. In some embodiments of the sensor unit 310, for example, the working electrode 313W and the reference electrode 313R can include materials described for electrodes 113W and 113R, electrodes 213W and 213R, or other embodiments of the working and reference electrodes, as discussed herein. For example, the working electrode 313W can include platinum, iridium, and / or combinations thereof (e.g., a 90% platinum / 10% iridium working electrode, etc.), and the reference electrode 313R can include iridium (e.g., iridium oxide).

[0167] In some embodiments of the sensor unit 310, the wafer-based substrate 311 includes an area of ​​1 mm by 1.5 mm for side W and side L, respectively. In this and other exemplary embodiments of the sensor unit 310, the first working electrode 313W-1 and the second working electrode 313W-2 are spaced apart by a distance D from the first reference electrode 313R-1 and the second reference electrode 313R-2, respectively. An exemplary distance separating the working electrode(s) 313W and the reference electrode(s) 313R may be as small as 1 μm (1 micron) or greater than 1 micron. Similarly, for example, the first working electrode 313W-1 and the second working electrode 313W-2 may be spaced apart by a particular distance to ensure, for example, that no cross-communication occurs, i.e., no interference of signals from another electrode. Additionally or alternatively, the first working electrode 313W-1 and the second working electrode 313W-2 may be constructed around an insulator structure such that the two electrodes do not act as one electrode. The distance or gap between the working electrodes 313W-1 and 313W-2 may be as small as a micron or larger than a micron, for example, depending on the desired form and mating configuration for the intended use of the sensor unit 310 when delivered and placed in a host. Similarly, the distance or gap between the reference electrodes 313R-1 and 313R-2 may be as small as a micron or larger than a micron, for example. In this and other exemplary embodiments of the sensor unit 310, the working electrode 313W and the reference electrode 313R may be configured to have an area as previously described in Table 1.

[0168] For electrode temporariness, the reference electrode 313R can provide a complement balancer for the signal, which can allow for reduction or elimination of signal noise in signal processing (e.g., signal to noise analysis) by the signal conditioning unit 123 and / or data processing unit 121 of the electronic unit 120. In some embodiments of the sensor unit 310, for example, the working electrode 313W includes a membrane (such as, for example, membrane 419 discussed later in FIG. 4) designed for analyte specificity directed to a target analyte, e.g., glucose, oxygen, ketones, or other analytes. The working electrode 313W serves as a primary reaction site for electrochemical reaction-generated signals that can confirm that the sensor is detecting a fluid containing oxygen and / or glucose or ketones based on, among other things, the configuration of the working electrode with its chemical layer 119, e.g., the membrane permeability of the layer and the catalytic or reactive material. In an exemplary implementation using an IrO2 electrode, iridium oxide provides longevity for the sensor unit 310 as the electrode does not degrade or cease to function during electrochemical sensing operations, and iridium oxide effectively enables a self-perforating (but not endless) electrochemical reaction, which allows the reference electrode to remain functional in conjunction with the working electrode.

[0169] Based on the special design, materials, and spacing of the two electrodes, the working electrode 313W and the reference electrode 313R, the sensor unit 310 can be reduced in size and allow for a lower potential voltage to detect the target analyte(s) at the electrodes, thereby providing the sensor unit 310 with the ability to function for a longer period of time and with greater stability.

[0170] The sensor unit 310 includes an electrical conductivity sensor 316 that includes one or more electrodes (e.g., electrodes 316A, 316B, and 316C in the example shown in FIG. 3 ) that the sensor unit 310 can use to determine the presence of fluid and / or fluid properties, such as fluid permeability or conductivity properties (e.g., fluid flow rate, pressure, and / or viscosity), osmotic pressure, and / or osmotic pressure. In some embodiments, for example, the electrical conductivity sensor 316 can determine the presence of fluid on the sensor unit 310 by determining a change in an electrical signal (e.g., voltage or current) across at least any two of the electrodes of the electrical conductivity sensor 316, such as at least two of the electrodes 316A, 316B, 316C in the example shown in FIG. 3 . In this manner, for example, the electrical conductivity sensor 316 can provide a gate switch for the sensor unit 310 by monitoring at least two electrodes of the electrical conductivity sensor 316, and the output signal can be used as an indication of a fluid property (e.g., sufficient moisture above the sensor) and / or as a control signal for operating other components of the sensor unit 310 (e.g., an ON / OFF switch that applies a voltage for operation of the two-electrode electrochemical sensor electrode content 313).

[0171] For example, such implementations of the sensor unit 310 may excite (electrically stimulate) one or more of the electrodes 316A, 316B, and / or 316C to detect a parameter associated with bodily fluid exposed to the sensor unit 310, ensuring that the detected signal is detected in a fluid-rich environment. For example, as bodily fluid decreases, the signal detected via one or more of the electrodes 316A, 316B, and / or 316C may decrease to negligible levels, and such implementations may provide a second identifier for fluid permeation in parallel with analyte measurements detectable by the electrochemical sensor electrodes.

[0172] As an illustrative example, in certain implementations where the analyte sensor device 100 including the sensor unit 310 is deployed within the body, the in vivo analyte sensor device 100 may reside within a portion of the body that forms an interstitial cavity (or pocket). In such a situation, the electrical conductivity sensor 316 of the sensor unit 310 may detect a signal related to fluid permeation that may provide an indication of separation of the sensor from bodily fluids (sometimes referred to as pocket healing), which may be due to scar tissue formation or other reasons that the deployment site is potentially inadequate for sensing the desired analytes and environmental conditions. In some implementations, characterizing "pocket healing" at the sensor deployment site may indicate the need for replacement or new site selection. This may be important for certain types of implantable devices (to which the in vivo analyte sensor device 100 may be attached), where an indication of "pocket healing" may indicate a desired or undesirable outcome associated with the implantable device.

[0173] As an example of "pocket healing" detection, if the sensor unit 310 is in a moist environment and proper lubricity is present, the electrical conductivity sensor 316 (which can operate as a switch sensor) should connect; if the sensor unit 310 is not in a moist environment with proper lubricity, the electrical conductivity sensor 316 will not connect, such non-connection being an indicator of a "dry" interstitial pocket, etc. In another example, when an in vivo analyte sensor device 100 including the sensor unit 310 is deployed in neurology, the electrical conductivity sensor 316 of the sensor unit 310 can be implemented to provide a second identifier for fluid transmission from the artery, through the sheath neck, and into the sheath body or sac.

[0174] In some embodiments of the sensor unit 310, for example, electrodes of the electrical conductivity sensor 316 may be used as a conductive switch system. For example, as in the examples above, in some embodiments, for example, electrodes of the electrical conductivity sensor 316 may additionally or alternatively be used as additional electrochemical sensor electrodes for the electrochemical sensor electrode temporary 313, such as counter electrodes, or additional working or reference electrodes. For example, the use of electrodes from the electrical conductivity sensor 316 as additional working and / or reference electrodes may be used to modify (e.g., optimize) the performance of the electrochemical sensor electrode temporary 313 based on the modification of the desired ratio of functional working reference electrodes.

[0175] In some implementations, for example, the sensor unit 310 can detect the degree of hydration of the biological fluid on the sensor unit 310, e.g., the hydration of the membrane on the electrode(s), based on the potential charge on the conductivity sensor 316. For such implementations, for example, the sensor unit 310 can be operable to provide a rapid equilibration / calibration protocol, e.g., 30 minutes or less, for the exemplary analyte sensor device 100, where the electrodes 316A, 316B, etc. are pre-exposed through cascaded voltage cycles prior to sensor implementation. The exemplary equilibration / calibration protocol can improve the stability of a particular hydration level in the cover membrane, which can enable the membrane to react quickly with the biological fluid when the analyte sensor device 100 is inserted into a patient-user sensing location. A potential static charge can be applied to electrode(s) 316A, 316B, 316C (or a second parallel electrode array 318) such that when moisture is present around the sensor membrane, the charge is released, causing the membrane to swell and allowing a chemical reaction to occur, e.g., enhancing the hydration mechanism and shortening the onset period of sensor function.

[0176] 4 illustrates an exploded view of another exemplary embodiment of the sensor unit 110 of the analyte sensor device 100 having a plurality of two-electrode electrochemical sensor electrode temporary and a multi-electrode conductivity sensor assembly, shown in FIG. 4 as sensor unit 410. The sensor unit 410 includes a first two-electrode electrochemical sensor electrode temporary 412 and a second two-electrode electrochemical sensor electrode temporary 414, each disposed on an electrically insulating wafer-based substrate 411. In this example, the first electrochemical sensor electrode temporary 412 includes a first working electrode 413W-1 and a first reference electrode 413R-1, and the second electrochemical sensor electrode temporary 414 includes a second working electrode 413W-2 and a second reference electrode 413R-2. The sensor unit 410 may include an electrode pad area 416, for example, to provide an electrical conductivity sensor switch for the sensor unit 410. Additionally or alternatively, for example, the electrode pad area 416 can be configured to provide a second set of sensor electrode(s) for a two-electrode electrochemical sensor electrode content. In some embodiments, at least two electrodes of the electrode pad area 416 can function as switches to enable signal transmission to a processing unit of the electronics unit 120 in communication with the sensor unit 410, which can, for example, confirm that the electrodes are "on" for electrochemical sensing applications.

[0177] The sensor unit 410 includes a multi-layer membrane 419 coupled to at least the working electrodes 413W-1 and 413W-2 of the electrochemical sensor electrodes 412 and 414, respectively. The membrane 419 is structured to include an outer layer 419A that regulates the permeation of reactive species, and an inner layer 419B that is coupled to the outer layer and attachable to the electrochemical sensor electrodes 412 and 414, immobilizing a catalyst (e.g., GOx for the specific application of glucose sensing) to facilitate a reaction with the permeating reactive species for detection of a target analyte in a biological fluid exposed to the sensor unit 410 when deployed in vivo. The membrane 419 can be configured to have a variety of size thicknesses that can be tailored to the desired application of the sensor unit 410. For example, in some embodiments, the membrane 419 can have a thickness of 10 μm or less, or between 5 μm and 10 μm.

[0178] In some embodiments, for example, the membrane 419 may include a plurality of ripples 418 in the outer layer 419A presenting a three-dimensional profile of the membrane 419. For example, the plurality of corrugations 418 are configured to promote increased signal stability of the detected electrical signal and promote functional life of the electrochemical sensor electrode temporary(s), e.g., the first bielectrode electrochemical sensor electrode temporary 412 and the second bielectrode electrochemical sensor electrode temporary 414, by preventing fouling of the electrode, e.g., the working electrode. In some embodiments of the membrane 419 having the plurality of corrugations 418, the plurality of corrugations 418 may be configured to have a height (h1) in the range of 10 μm to 20 μm. In some embodiments, for example, the spacing between ripples (peak to peak) of the plurality of ripples of the membrane 419 may include 500 nm or more, e.g., 500 nm to 5 μm, etc.

[0179] In some embodiments, similar to the example shown in FIG. 4, the electrically insulating wafer-based substrate 411 of the sensor unit 410 includes a raised surface 421 structured to include a plurality of peaks and valleys on the upper surface of the substrate 411. The peaks and valleys of the raised surface 421 can be uniformly (e.g., periodically) or non-uniformly (e.g., periodically) configured. The electrochemical sensor electrode temporary(s) and multi-electrode conductivity sensor assembly(s) are bonded to the wafer-based substrate 411 to take the shape of the raised surface 421. In some optional embodiments, for example, the sensor unit 410 includes a flexible material layer 422 (e.g., polyimide) bonded between the sensor temporary and / or assembly and the raised surface 421 of the wafer-based substrate 411.

[0180] In FIG. 4, cut-out insert 442 is shown illustrating ripples 418 on the top surface of an exemplary membrane 419. In this example, the ripples 418 of membrane 419 include an exemplary peak-to-valley height (h1) in the range of about 10 μm to 20 μm. In an exemplary embodiment of membrane 419, the ride height from peak to valley may include a range of about 5 μm to 50 μm. FIG. 4 also shows cut-out insert 444 showing a close-up of the peaks and valleys of the raised surface 421 of substrate 411, showing an exemplary peak-to-valley height (h2) of the raised surface 421 in the range of about 20 μm to about 200 μm, for example. In some embodiments, for example, the spacing between the ridges (peak to peak) of the raised surface 421 of substrate 411 includes 1 μm or more, such as 1 μm to 5 μm.

[0181] The sensor unit 410 is designed to provide a surface profile, including, for example, in some embodiments, ripples 418 from the top surface of the membrane 419 and / or the ridges 421 of the substrate 411, that promotes the functional longevity of the sensor unit 410 in the analyte sensor device 100 when deployed in the subject's body. This three-dimensional surface profile can increase the surface area of ​​the membrane 419 while remaining in the same minimum size footprint of the sensor conditions 412, 414 on the wafer-based substrate 411, and therefore, for example, enable signal consistency and longevity of the reaction without fouling the surface during use to generate a detectable signal associated with the target analyte. For example, the peak-to-valley surface profile of the membrane 419, which may be fabricated based on, for example, the initial profile of the ridged surface 421 of the substrate 411, can inhibit cell endothelialization on the sensor and act as a coating on the membrane that would otherwise inhibit or block the interaction of the membrane 419 with biological fluids in contact with the sensor, thus preventing analyte sensing. Additionally, the three-dimensional (e.g., corrugated and ridged) surface profile of the sensor unit 410 can act as a "used layer" or oxide coating while allowing additional reaction and surface exposure to chemicals. For example, the three-dimensional profile of the sensor unit 410 can provide the sensor unit 410 with a permeability function that allows transport of desired reactive species that support electrochemical sensing of target analytes while degrading over time to a level that does not affect the permeability or functionality of the membrane. The composition and structure of the membrane 419 can be configured for management of signal detection based, for example, on membrane stoichiometry and viscosity, which can vary for a particular sensing application in a particular region of a patient's body in which the analyte sensor device 100 is deployed. In some implementations, the particular regions of the sensor unit 410 for coating with the membrane 419 can be controlled by a material application process, including a micro / angstrom liter drop process or a drop spin coat process.

[0182] 4, the height (h1) of the ripples 418 of the membrane 419 can be about 20 μm from peak to valley. This height of the ripples 418 of the membrane 419 can enable the sensor unit 410 to maintain a measurement point (peak to valley) from the contact surface on the working electrode 413 to the top of the membrane 419 above that surface. In some embodiments, the height of the ripples 418 of the membrane 419 is 10 μm or less from peak to valley, enhancing membrane permeability and functionality, for example, for detection of glucose, oxygen, and other analytes.

[0183] In some embodiments of the sensor unit 410, for example, the ripples 418 of the membrane 419 are created based on a coating fabrication on the raised surface 421 of the wafer-based substrate 411, i.e., the rippled surface of the membrane 419 can take on the raised profile of the sensor unit 410 (e.g., sensor regions 412, 414, electrode pad area 416, substrate 411) based on the fabricated raised surface 421 of the substrate 411. Additionally or alternatively, in some embodiments of the sensor unit 410, for example, the ripples 418 of the membrane 419 are generated on the outer surface 418 of the membrane 419.

[0184] In some exemplary implementations, one or more analyte sensor devices 100 may be coupled to an implant device, such as a total knee replacement (TKR) device, a stent, a shirt, or other implantable device. In some implementations where the implant device includes a power source, for example, the analyte sensor device 100 may be integrated with the implant device to utilize power provided by the implant device. In some exemplary embodiments, one or more analyte sensor devices 100 may be independently positioned within a patient user's body (e.g., not attached to another implant device or structure), configured such that when the entire in vivo analyte sensor device 100 is fully inserted under the user's skin (e.g., below the hair follicle for exposure to interstitial fluid or blood that allows hydration of a functionalized layer to facilitate reaction of the target analyte and the sensor electrodes), the in vivo analyte sensor device 100 may be operational within two hours of insertion.

[0185] FIG. 5 shows a diagram illustrating a method 500 for deploying and activating a stand-alone in-vivo analyte sensor device 100 in a subject according to the present technology. Method 500 includes a process 505 for preparing a location on the subject's body where the in-vivo analyte sensor device 100 is inserted, which may include, for example, shaving the skin and wiping the skin with an antiseptic solution such as alcohol, iodine, etc. Method 500 includes a process 510 for inserting the in-vivo analyte sensor device 100 under the skin. In an implementation of process 510, a sensor placement is selected to protect against unwanted or external fluid and / or temperature interference. Method 500 includes a process 515 for wirelessly connecting the in-vivo analyte sensor device 100 to communicate with a receiver device 130. The method 500 includes a process 520 of communicating with the electronics unit 120 of the in vivo analyte sensor device 100 and a data processing unit (e.g., resident on the receiver device 130, the client computing device 154 of the data processing system 150, and / or the remote computing device 160) to monitor hydration of the electrodes of the sensor unit 110. The method 500 includes a process 525 for performing a self-calibration of the in vivo analyte sensor device 100, where an independent analyte test is performed by / for the subject and the results are submitted to the receiver device 130 and / or the data processing system 150 for analysis in comparison to initial data obtained from the sensor unit 110. In an exemplary implementation, the process 525 calibrates the in vivo analyte sensor device 100 to verify the sensor and monitoring functions of an app running on the receiver device 130 and / or the client computing device 154 of the data processing system 150. Upon performance of method 500, the in vivo analyte sensor device 100 can function for its intended use and duration in sensing primary analytes (e.g., glucose and / or oxygen and / or ketones) and secondary analytes or physiological factors, including, but not limited to, temperature, vibration, water, or others, at the deployment site of the in vivo analyte sensor device 100.In some implementations, the method 500 may be repeated for a new sensor after the in vivo analyte sensor device 100 expires, which may be 90 days or more, including 1 year or more, for certain exemplary embodiments of the in vivo analyte sensor device 100.

[0186] In additional embodiments, the present disclosure provides methods of detecting the presence of an analyte in a biological fluid and optionally measuring the amount of the analyte. For example, the present disclosure provides methods of detecting the presence of an analyte in a biological fluid in vivo, the method comprising implanting a sensor device as described herein inside a patient, e.g., a sensor device of any of the apparatus embodiments identified herein, exposing the sensor device to the biological fluid inside the patient, generating an electrical signal by the sensor device responsive to the presence of the analyte in the biological fluid, converting the electrical signal into an observable indication of the presence of the analyte in the biological fluid, and optionally the sensor device displaying and / or transmitting data associated with the electrical signal; and (2) a method of detecting the presence of an analyte in a biological fluid ex vivo, the method comprising placing a sensor device as described herein on a surface of a patient, e.g., a sensor device of any of the device embodiments identified herein, exposing the sensor device to the biological fluid on the surface of the patient, and generating an electrical signal by the sensor device responsive to the presence of the analyte in the biological fluid. (3) a method for detecting the presence of an analyte in a biological fluid ex vivo, the method comprising positioning a sensor device as described herein on a medical device including a biological fluid conduit, e.g., a catheter, a sensor device of any of the device embodiments identified herein, exposing the sensor device to the biological fluid contained within the biological fluid conduit, generating an electrical signal by the sensor device in response to the presence of the analyte in the biological fluid, converting the electrical signal to an observable indication of the presence of the analyte in the biological fluid, and optionally the sensor device displaying and / or transmitting data associated with the electrical signal; and (4) a method for detecting the presence of an analyte in a biological fluid in vitro, the method comprising positioning a sensor device as described herein on a medical device including a biological fluid conduit, e.g., a catheter, a sensor device of any of the device embodiments identified herein, exposing the sensor device to the biological fluid contained within the biological fluid conduit, generating an electrical signal by the sensor device in response to the presence of the analyte in the biological fluid, converting the electrical signal to an observable indication of the presence of the analyte in the biological fluid, and optionally the sensor device displaying and / or transmitting data associated with the electrical signal.For example, a method comprising a sensor device of any of the device embodiments identified herein and at an in vitro location, exposing the sensor device to the biological fluid at the in vitro location, generating an electrical signal by the sensor device responsive to the presence of the analyte in the biological fluid, converting the electrical signal into an observable indication of the presence of the analyte in the biological fluid, and optionally the sensor device displaying and / or transmitting data associated with the electrical signal.

[0187] The biological fluid may be a fluid present within the host, or the biological fluid may be a fluid that exits the host, for example blood that exits the host by blood sampling, or through a catheter or other biological fluid conduit connected to the host, or by bleeding due to trauma, for example a cut in the host. Thus, biological fluid may refer to fluid present in the host as well as fluid that exits the host, optionally in modified form, for example in concentrated form due to evaporation of water from the biological fluid. The sensor may be implanted within the host, in which case an in vivo biological fluid is monitored. The sensor may be located entirely on the surface of the host, or within a medical device, such as a catheter or other conduit connected to the host that can carry fluid from the host, in which case an ex vivo biological fluid is monitored. The sensor may be placed in an in vitro location, such as a laboratory device that is not physically connected to the host, in which case an in vitro biological fluid is monitored. In one embodiment, the analyte is glucose, and the sensor detects the presence of glucose in the biological fluid. In one embodiment, the analyte is glucose and the sensor detects and obtains data reflective of the amount of glucose in the biological fluid, hi one embodiment, the biological fluid is blood.

[0188] The sensor device is exposed to the biological fluid, or in other words, the biological fluid is in contact with the sensor device. Such exposure or contact includes situations where the sensor device is in continuous contact with the biological fluid and periodically monitors the presence of the analyte. Upon sensing the analyte, the sensor device responds by generating an electrical signal, the characteristics of which may also indicate the amount or concentration of the analyte in the biological fluid. The electrical signal may be converted into an observable indication of the presence and / or amount of the analyte in the biological fluid. For example, the observable indication may be a display that is a component of the sensor device, and the display may show a number that indicates the amount of the analyte detected by the sensor device. As another example, the electrical signal may be transmitted, either wirelessly or via a wired connection, to a separate device, e.g., a laptop or a smartphone, which generates an observable indication of the presence and / or amount of the analyte. Optionally, the electrical signal may cause data to be stored in a memory, e.g., a memory chip, of the sensor device, where the data reflects the presence and / or amount of the analyte in the sample fluid, and the data is stored until it is converted into an observable indication of the presence and / or amount of the analyte in the sample, i.e., detection of the analyte in the sample.

[0189] Working Example In some embodiments according to the present technology (Example A1), a sensor device for in vivo or ex vivo monitoring of an analyte comprises: a sensor device comprising a substrate comprising a non-conductive material; and an electrochemical sensor electrode disposed on the substrate and configured to detect a target analyte in a bodily fluid when the electrochemical sensor electrode is fully deployed within a subject's body; the sensor device comprises a temporary part of the electrochemical sensor electrode, or optionally a working electrode and a reference electrode associated with the working electrode; the working electrode is functionalized with a chemical layer configured to promote a reaction involving the target analyte that generates an electrical signal at the electrochemical sensor electrode; and an electronic unit in communication with the electrochemical sensor electrode temporary part; the electronic unit comprises a wireless communication unit comprising a wireless transmitter or wireless transceiver for transmitting data associated with the electrical signal to an external processor.

[0190] Example A2 includes a sensor device described in any of Examples A1-A45, wherein the processor is operable to determine a parameter associated with the target analyte based on the electrical signal measured at the time of the electrochemical sensor electrode, and the processor is configured to temporarily determine a change in environmental condition within a deployment zone from the same electrical signal generated at the electrochemical sensor electrode when the electrochemical sensor electrode is deployed within a subject's body.

[0191] Example A3 includes the sensor device of any of Example A2 or Examples A1-A45, where the change in environmental condition includes one or more of a change in temperature, a change in moisture, or a change in osmotic pressure.

[0192] Example A4 includes a sensor device described in any of Example A2 or Examples A1-A45, wherein the change in environmental condition includes a change in temperature, and the determined change in temperature indicates temperature stability within the deployment zone and at least a potential infection within or near the deployment zone.

[0193] Example A5 includes a sensor device described in any of Example A2 or Examples A1-A45, wherein the change in environmental condition includes a change in temperature and the determined change in temperature is information about a change in magnitude of temperature within the deployment zone.

[0194] Example A6 includes a sensor device as described in any of Examples A2-A5 to A5 or any of Examples A1-A45, wherein a determined change in temperature is compared to a threshold and an alarm is generated when the determined change exceeds the threshold.

[0195] Example A7 includes a sensor device described in any of Example A2 or Examples A1-A45, wherein the change in environmental condition includes a change in osmolality, and the determined change in osmolality indicates the stability of the salt concentration in the placement zone and potential dehydration at least in or near the placement zone.

[0196] Example A8 includes the sensor device of Example A7 or any of Examples A1-A45, wherein the determined change in osmolality is compared to a threshold value and an alarm is generated when the determined change exceeds the threshold value.

[0197] Example A9 includes a sensor device of any of Examples A1-A451, further comprising a plurality of electrodes disposed on a substrate and configured to detect a parameter associated with electrical conductivity of bodily fluid across at least two of the plurality of electrodes when the sensor device is deployed within a subject's body.

[0198] Example A10 includes a sensor device described in any of Example A9 or Examples A1-A45, wherein at least two electrodes are configured to operate as an AND gate, such that when bodily fluid contacts both of the two electrodes, a short circuit occurs across the two electrodes, corresponding to one of the AND gates and one signal detectable by the sensor device.

[0199] Example A11 includes the sensor device of example A9 or A10 or any of examples A1-A45, wherein at least some of the electrodes of the plurality of electrodes are at least partially covered by a permeable membrane.

[0200] Example A12 includes the sensor device of any of Examples A1-A45, where the substrate includes a top surface having a plurality of ridges to provide a three-dimensional profile to the sensor device.

[0201] Example A13 includes the sensor device of any of examples A12 or A1-A45, where the substrate is a wafer-based substrate including at least one of silicon oxide, germanium, or gallium arsenide.

[0202] Example A14 includes the sensor device of Example A12 or A13, or any of Examples A1-A45, where the electrochemical sensor electrode temporary material has a morphology corresponding to the three-dimensional profile.

[0203] Example A15 includes the sensor device of Example A14 or any of Examples A1-A45, wherein the working electrode and the reference electrode are disposed on at least a portion of one or more of the plurality of ridges of the substrate.

[0204] Example A16 includes a sensor device according to any of Examples A12 or A13, or Examples A1-A45, in which the chemical layer has a morphology corresponding to a three-dimensional profile.

[0205] Example A17 includes the sensor device of any of Examples A1-A45, wherein the reference electrode includes iridium.

[0206] Example A18 includes the sensor device of any of Example A17 or Examples A1-A45, wherein the reference electrode includes iridium oxide.

[0207] Example A19 includes the sensor device of example A17 or A18, or any of examples A1-A45, wherein the sensor device can maintain a constant and stable reference signal for the detected electrical signal for at least 12 months.

[0208] Example A20 includes the sensor device of Example A17 or A18, or any of Examples A1-A45, wherein the sensor device is operable to detect a target analyte with low power consumption based on an applied voltage of less than 300 mV, or less than 285 mV, or less than 175 mV at the reference electrode.

[0209] Example A21 includes the sensor device of example A17 or A18, or any of examples A1-A45, where the sensor device is configured to prevent detectable interference signals caused by dopamine, aspirin, acetaminophen, numbing chemicals for pain treatment, or other secondary chemical elements.

[0210] Example A22 includes the sensor device of any of Examples A1-A45, wherein the working electrode includes at least one of platinum, iridium, gold, silver, titanium, single-walled or multi-walled carbon nanotubes, or an alloy.

[0211] Example A23 includes the sensor device of Example A22 or any of Examples A1-A45, wherein the working electrode includes platinum and iridium.

[0212] Example A24 includes the sensor device of any of Examples A1-A45, wherein the working electrode is functionalized with the chemical layer configured to interact with the target analyte to promote a reaction resulting in a change in charge potential or flow at or near the surface of the working electrode, and an electrical signal associated with the reaction is detectable at the working electrode relative to the reference electrode, configured to measure a parameter associated with the target analyte.

[0213] Example A25 includes the sensor device of Example A24 or any of Examples A1-A45, wherein the chemical layer includes a membrane including: (i) an outer layer exposed to the bodily fluid configured to regulate permeation of a reactive species including the target analyte; and (ii) an inner layer coupled between the outer layer and the surface of the working electrode, immobilizing a catalyst capable of promoting the reaction by the permeating reactive species for detection of the target analyte at the working electrode.

[0214] Example A26 includes the sensor device of any of Example A24 or Examples A1-A45, wherein the chemical layer includes a membrane including: (i) an outer layer exposed to the body fluid configured to regulate permeation of a reactive species including the target analyte; and (ii) an inner layer bonded between the outer layer and the surface of the working electrode, immobilizing a catalyst capable of promoting the reaction by the permeating reactive species for detection of the target analyte at the working electrode; and an outer film including a plurality of corrugations on a top surface of the outer layer.

[0215] Example A27 includes the sensor device of example A26 or any of examples A1-A45, wherein the membrane comprises a thickness less than or equal to 10 μm, or between 5 μm and 10 μm.

[0216] Example A28 includes the sensor device of example A26 or any of examples A1-A45, wherein the plurality of corrugations on the top surface of the outer layer include a height in the range of 10 μm to 20 μm.

[0217] Example A29 includes the sensor device of Example A26 or any of Examples A1-A45, wherein the plurality of ripples on the upper surface of the outer layer are configured to promote the functional life of the electrochemical sensor electrode based on increasing the signal stability of the detected electrical signal and preventing fouling of the working electrode.

[0218] Example A30 includes a sensor device of any of Examples AA26-29 or any of Examples A1-A45, wherein the plurality of corrugations of the membrane are at least partially formed by the membrane conformed onto the three-dimensional surface of the substrate.

[0219] Example A31 includes a sensor device described in any of Examples A1-A45, wherein the electronic unit further includes a signal conditioning unit in communication with the electrochemical sensor electrodes via one or more electrical interface components, the signal conditioning unit including an electrical circuit configured to process the detected electrical signal by one or more of amplifying the electrical signal, filtering the electrical signal, or converting the electrical signal from analog to digital.

[0220] Example A32 includes a sensor device described in any of Example A31 or Examples A1-A45, wherein the electronic unit further comprises a data processing unit in communication with the signal conditioning unit, the data processing unit comprising a processor and a memory and configured to process the electrical signal as data representative of one or more parameters of the target analyte.

[0221] Example A33 includes a sensor device described in any of Examples A1-A45, comprising an electrical interconnect wire and an electrical interface contact site disposed on a substrate, the electrical interconnect wire being bonded between the temporary contact site of the electrochemical sensor electrode and the electrical interface contact site.

[0222] Example A34 includes the sensor device of Example A33 or any of Examples A1-A45, wherein the electrical interconnect wires disposed on the substrate are hermetically sealed with a non-permeable material covering the electrical interconnect wires to provide an electrical shield from the body fluid.

[0223] Example A35 includes the sensor device of example A34 or any of examples A1-A45, wherein the non-permeable material includes at least one of a parylene, a urethane, or a Teflon material.

[0224] Example A36 includes a sensor device of any of Examples A1-A45, comprising a casing that encases the electronic unit and protects the electronic unit from exposure to bodily fluids, and at least partially encases the electrochemical sensor electrodes such that the working electrode and reference electrode are exposed to bodily fluids when the sensor device is deployed within a subject's body.

[0225] Example A37 includes the sensor device of example A36 or any of examples A1-A45, wherein the casing includes one or both of a flat side or a curved side to provide a form factor for the sensor device.

[0226] Example A38 includes the sensor device of example A36 or any of examples A1-A45, wherein the shape of the sensor device includes at least one of a rectangular shape, a cylindrical shape, a conical shape, an elliptical shape, a pyramidal shape, a trapezoidal shape, or a non-uniform shape.

[0227] Example A39 includes the sensor device of any of Examples A1-A45, comprising a second electrochemical sensor electrode disposed on the substrate and configured to detect a second target analyte in the bodily fluid when the second electrochemical sensor electrode is fully deployed within the subject's body, the second electrochemical sensor electrode being a part of the device, and optionally comprising a second working electrode and a second reference electrode associated with the second working electrode, the second working electrode being functionalized with a second chemical layer configured to promote a reaction involving the second target analyte that generates a second electrical signal at the second electrochemical sensor electrode.

[0228] Example A40 includes a sensor device described in any of Examples A1-A45, comprising one or more conductive pads disposed on a substrate configured to be electrically stimulated to detect a parameter associated with a bodily fluid temporarily exposed to an electrochemical sensor electrode.

[0229] Example A41 includes the sensor device described in Example A40 or any of Examples A1-A45, and the one or more conductive pads can ensure that the detected electrical signal is detected in a fluid-rich environment.

[0230] Example A42 includes a sensor device of any of examples A40 or A1-A45, wherein one or more conductive pads can reduce noise associated with the detected signal to a negligible level.

[0231] Example A43 includes a sensor device of any of Examples A1-A45, wherein the target analyte includes one or more of glucose, oxygen, ketones, water, amino acids, nucleic acids, lipids, proteins, carbohydrates, liposomes, nanoparticles, or pharmacological drugs.

[0232] Example A44 includes a sensor device described in any of Examples A1-A45, wherein the sensor device is configured to detect the target analyte as a primary biomarker indicative of a health status of the subject and to detect a secondary biomarker simultaneously with the primary biomarker, the secondary biomarker including a physiological parameter including one or both of temperature and vibration, and the physiological parameter is detected based on a signal analysis of the detected electrical signal by the electrochemical sensor electrode.

[0233] Example A45 includes a sensor device of any of Examples A1-A44, wherein the sensor device is operable to be inserted beneath the subcutaneous layer of a subject and within an interstitial pocket of a subject such that the sensor can detect and determine whether there is a sufficient pool of interstitial fluid within the interstitial pocket to obtain an electrical signal associated with a target analyte.

[0234] In some embodiments according to the present technology (Example A46), a sensor device for in vivo or ex vivo monitoring of an analyte comprises a substrate comprising a non-conductive material, and an electrochemical sensor electrode disposed on the substrate, the substrate being a wafer-based substrate comprising silicon oxide and comprising a top surface having a plurality of ridges to provide a three-dimensional profile for the sensor device, the electrochemical sensor electrode being configured to detect a target analyte in a bodily fluid when the electrochemical sensor electrode is fully deployed within a body of a subject, the electrochemical sensor electrode comprising a temporary part of the electrochemical sensor electrode and optionally a working electrode and a reference electrode associated with the working electrode, the electrochemical sensor electrode temporary part having a form corresponding to the three-dimensional profile provided by the substrate, the working electrode functionalized with a chemical layer configured to promote a reaction involving the target analyte that generates an electrical signal at the electrochemical sensor electrode temporary part, the reference electrode comprising iridium oxide, the working electrode comprising platinum and iridium, and the sensor device detecting a voltage of less than 300 mV at the reference electrode based on an applied voltage of less than 300 mV at the reference electrode. , or is operable to detect the target analyte with low power consumption, or less than 285mV, or less than 175mV, the chemical layer comprising a membrane comprising: (i) an outer layer exposed to the bodily fluid configured to regulate permeation of reactive species including the target analyte; and (ii) an inner layer coupled between the outer layer and the surface of the working electrode to immobilize a catalyst capable of facilitating the reaction by the permeating reactive species for detection of the target analyte at the working electrode, the membrane comprising a plurality of corrugations on an upper surface of the outer layer; and a plurality of electrodes disposed on the substrate and configured to detect a parameter associated with electrical conductivity of the bodily fluid across at least two of the plurality of electrodes when the sensor device is deployed within the subject's body, the at least two electrodes configured to operate as an AND gate, such that when the bodily fluid contacts both of the two electrodes, a short circuit occurs across the two electrodes corresponding to one of the AND gates and a signal detectable by the sensor device; and an electronic unit in communication with the electrochemical sensor electrode temporary component, the electronic unit comprising:a wireless communication unit including a wireless transmitter or transceiver for transmitting data associated with the electrical signal to an external processor, wherein the processor is operable to determine a parameter associated with the target analyte based on the electrical signal measured at the electrochemical sensor electrode, and wherein the processor is configured to determine from the same electrical signal generated at the electrochemical sensor electrode a change in environmental conditions, including temperature, within a deployment zone when the electrochemical sensor electrode is deployed within the subject's body;

[0235] Example A47 includes the sensor device of example A46, where the sensor device includes at least one feature of any of examples A2-A45.

[0236] In some embodiments according to the present technology (Example A48), a sensor device for in vivo or ex vivo monitoring of an analyte comprises: a substrate comprising a non-conductive material; and an electrochemical sensor electrode disposed on the substrate and configured to detect a target analyte in a bodily fluid when the electrochemical sensor electrode is fully deployed in a subject's body; a temporary part of the electrochemical sensor electrode, and optionally a working electrode and a reference electrode associated with the working electrode, the working electrode being functionalized with a chemical layer configured to promote a reaction involving the target analyte that generates an electrical signal at the electrochemical sensor electrode; and an electronic unit in communication with the electrochemical sensor electrode temporary part, the electronic unit comprising a wireless communication unit including a wireless transmitter or wireless transceiver for transmitting data associated with the electrical signal to an external processor.

[0237] Example A49 includes the sensor device of example A46, where the sensor device includes at least one feature of any of examples A2-A45.

[0238] In some embodiments according to the present technology (Example A50), a system is provided comprising a sensor device for in vivo or ex vivo monitoring of an analyte, the system comprising: a substrate comprising a non-conductive material; and an electrochemical sensor electrode disposed on the substrate and configured to detect a target analyte in a bodily fluid when the electrochemical sensor electrode is fully deployed within a subject's body, the electrochemical sensor electrode comprising a working electrode and a reference electrode associated with the working electrode, the working electrode being functionalized with a chemical layer configured to promote a reaction involving the target analyte that generates an electrical signal at the electrochemical sensor electrode.

[0239] Example A51 includes the sensor device of example A50, where the sensor device includes at least one feature of any of examples A2-A45.

[0240] In some embodiments according to the present technology (Example A52), a system for analyte and environmental sensing includes a sensor device and a data processing system. The sensor device is operable to be placed at least partially in the body of a patient-user, the sensor device comprises a substrate comprising a non-conductive material, an electrochemical sensor electrode disposed on the substrate and configured to detect a target analyte in a bodily fluid when the electrochemical sensor electrode is fully deployed in the body of a patient-user, a temporary part of the electrochemical sensor electrode, and optionally a working electrode and a reference electrode associated with the working electrode, the working electrode is functionalized with a chemical layer configured to promote a reaction with the target analyte that generates an electrical signal at the electrochemical sensor electrode, and an electronic unit in communication with the electrochemical sensor electrode temporary part, the electronic unit comprises a wireless communication unit including a wireless transmitter or a wireless transceiver for transmitting data associated with the electrical signal to an external processor, the electronic unit according to claim 1. The data processing system comprises a processor and a memory, and is configured to be in data communication with the sensor device, receive data from the sensor unit, and process the received data to indicate a parameter associated with a target analyte and / or an environmental condition in an area where the electrochemical sensor electrodes are deployed.

[0241] Example A53 includes a system in which the sensor device is any of examples A52-A58, any of examples A4A46-A47A1-A45A48-A49.

[0242] Example A54 includes a system described in any of Examples A52-A58, wherein the data processing system includes a server computer having a processor and memory, and one or more databases in data communication with the server computer, and the data processing system is configured to remotely monitor data associated with a patient-user acquired by the sensor device.

[0243] Example A55 includes a system described in any of Examples A52-A58, further including a receiver device including a processor and memory operable to (i) receive wirelessly transmitted data carrying electrical signals obtained from the sensor device, and (ii) transmit the data to a data processing system.

[0244] Example A56 includes the system of example A55 or any of examples A52-A58, wherein the receiver device is configured to store the data in a memory of the receiver device.

[0245] Example A57 includes the system of example A55 or any of examples A52-A58, wherein the receiver devices communicate with each other and with the data processing system via a network of computers accessible via the Internet.

[0246] Example A58 includes a system described in any of examples A52-A57, further including a remote client computing device including a processor and memory configured to data communicate with the data processing system and receive processed data that is selected, filtered, and / or formatted by the data processing system.

[0247] conclusion Implementations of the subject matter and functional operations described in this patent document may be implemented in various systems, digital electronic circuits, or computer software, firmware, or hardware, including the structures disclosed herein and their structural equivalents, or in any combination of one or more of them. Implementations of the subject matter described herein may be implemented as one or more computer program products, i.e., one or more modules of computer program instructions encoded on a tangible and non-transitory computer-readable medium for execution by or for controlling the operation of a data processing device. The computer-readable medium may be a machine-readable storage device, a machine-readable storage substrate, a memory device, a composition of matter affecting a machine-readable propagated signal, or one or more combinations thereof. The term data processing unit or data processing apparatus encompasses all apparatus, devices, and machines for processing data, including, for example, a programmable processor, a computer, or multiple processors or computers. An apparatus may include, in addition to hardware, code that creates an environment for the execution of the computer program in question, such as code constituting a processor firmware, a protocol stack, a database management system, an operating system, or one or more combinations thereof.

[0248] A computer program (also known as a program, software, software application, script, or code) can be written in any form of programming language, including compiled or interpreted languages, and can be deployed in any form, including as a stand-alone program or as a module, component, subroutine, or other unit suitable for use in a computing environment. A computer program does not necessarily correspond to a file in a file system. A program can be stored in part of a file that holds other programs or data (e.g., one or more scripts stored in a markup language document), in a single file dedicated to the program in question, or in several coordinated files (e.g., a file that stores one or more modules, subprograms, or portions of code). A computer program can be deployed to be executed on one computer, or on several computers located at one site or distributed across several sites and interconnected by a communication network.

[0249] The processes and logic flows described herein may be implemented by one or more programmable processors executing one or more computer programs to perform functions by operating on input data and generating output. The processes and logic flows may also be implemented by, and an apparatus may be implemented as, special purpose logic circuitry, such as an FPGA (field programmable gate array) or an ASIC (application specific integrated circuit).

[0250] Processors suitable for executing a computer program include, by way of example, both general purpose and special purpose microprocessors, as well as any one or more processors of any kind of digital computer. Typically, a processor receives instructions and data from a read-only memory or a random access memory, or both. The essential elements of a computer are a processor for executing instructions and one or more memory devices for storing instructions and data. Generally, a computer also includes, or is operatively coupled to receive data from, or transfer data to, one or more mass storage devices for storing data, such as, for example, magnetic disks, magneto-optical disks, or optical disks. However, a computer need not have such devices. Suitable computer-readable media for storing computer program instructions and data include all forms of non-volatile memory, media, and memory devices, examples of which include, for example, semiconductor memory devices, such as, for example, EPROM, EEPROM, and flash memory devices. The processor and memory may be supplemented by, or incorporated in, special purpose logic circuitry.

[0251] This specification, together with the drawings, where illustrative examples are meant to be exemplary only. As used herein, the singular forms "a," "an," and "an" are intended to include the plural forms unless the context clearly indicates otherwise. Further, the use of "or" is intended to include "and / or" unless the context clearly indicates otherwise.

[0252] Although this patent document contains many details, these should not be interpreted as limitations on the scope of any invention or claims, but as descriptions of features that may be specific to certain embodiments of a particular invention. Certain features described in this patent document in the context of separate embodiments can also be implemented in combination in a single embodiment. Conversely, various features described in the context of a single embodiment can also be implemented in multiple embodiments separately or in any suitable subcombination. Furthermore, even if features may be described above as acting in a particular combination and are initially claimed as such, one or more features from the claimed combination may, in some cases, be separated from the combination, and the claimed combination may be directed to a subcombination or variation of the subcombination.

[0253] Similarly, although operations are illustrated in the figures in a particular order, this should not be understood as requiring that such operations be performed in the particular order shown, or in any sequential order, or that all of the illustrated operations be performed to achieve a desired result. Further, the separation of various system components in the embodiments described in this patent document should not be understood as requiring such separation in all embodiments.

[0254] Only some implementations and examples have been described; other implementations, enhancements, and variations can be made based on what is described and illustrated in this patent document.

Claims

1. 1. A sensor device for in vivo monitoring of an analyte, comprising: a substrate comprising a non-conductive material, the substrate being a silicon oxide wafer-based substrate, the substrate including a top surface having a plurality of ridges for providing a three-dimensional profile to the sensor device; the sensor device has an electrochemical sensor electrode assembly disposed on the substrate, configured to detect a target analyte in a bodily fluid when the electrochemical sensor electrode assembly is fully deployed within a subject's body, the electrochemical sensor electrode assembly comprising a working electrode and a reference electrode associated with the working electrode, the electrochemical sensor electrode assembly having a morphology corresponding to a three-dimensional profile of the substrate, the working electrode being functionalized with a chemical layer that promotes a reaction involving the target analyte and generates an electrical signal, the reference electrode comprising iridium oxide and the working electrode comprising platinum and iridium, and the sensor device is capable of detecting the target analyte with low power consumption based on a voltage applied to the reference electrode being greater than or equal to about 110 mV and less than 300 mV, or less than 285 mV, or less than 175 mV; the chemical layer comprises a membrane including: (i) an outer layer exposed to the body fluid and configured to regulate permeation of reactive species including the target analyte; and (ii) an inner layer coupled between the outer layer and a surface of the working electrode, the inner layer immobilizing a catalyst capable of promoting a reaction with the permeated reactive species for detection of the target analyte at the working electrode, the membrane having a plurality of corrugations on an upper surface of the outer layer; the sensor device further comprises a plurality of electrodes disposed on the substrate and configured to detect a parameter associated with electrical conductivity of the bodily fluid across at least two of the plurality of electrodes when the sensor device is deployed within the subject's body, the at least two electrodes configured to operate as an AND gate such that when the bodily fluid is in contact with both of the two electrodes, a short circuit occurs across the two electrodes corresponding to a signal of the AND gate detectable by the sensor device; the sensor device further comprises an electronic unit in communication with the electrochemical sensor electrode assembly, the electronic unit comprising a wireless communication unit including a wireless transmitter or transceiver, and transmitting data relating to the electrical signal to an external processor; The sensor device is characterized in that the external processor is operable to determine parameters related to the target analyte based on the electrical signal measured by the electrochemical sensor electrode assembly, and is configured to determine changes in environmental conditions, including temperature, within a deployment zone when the electrochemical sensor electrode assembly is deployed within the subject's body.

2. The sensor device of claim 1 , wherein the determined temperature change is indicative of the stability of the temperature within the deployment zone and a potential infection at least within or near the deployment zone.

3. The sensor device of claim 1 , wherein the determined change in temperature is compared to a threshold value and generates an alarm when the change exceeds the threshold value.

4. The sensor device of claim 1 , wherein the determined change in the environmental condition comprises a change in osmotic pressure.

5. The sensor device of claim 1 , wherein at least some of the plurality of electrodes are at least partially covered by a permeable membrane.

6. The sensor device of claim 1 , wherein the working electrode and the reference electrode are disposed on at least a portion of the plurality of ridges of the substrate.

7. The sensor device of claim 1 , wherein the chemical layer has a morphology that corresponds to the three-dimensional profile.

8. The sensor device of claim 1 , wherein the reference electrode comprises iridium.

9. 10. The sensor device of claim 1, wherein the sensor device is capable of maintaining a constant and stable reference signal for the detected electrical signal for at least 12 months.

10. 10. The sensor device of claim 1, wherein the sensor device is configured to prevent detectable interfering signals caused by secondary chemical elements including dopamine, aspirin, acetaminophen, or numbing chemicals for pain treatment.

11. 10. The sensor device of claim 1, wherein the working electrode comprises at least one of gold, silver, titanium, single-walled or multi-walled carbon nanotubes, or alloys.

12. 10. The sensor device of claim 1, wherein the working electrode is functionalized with the chemical layer configured to interact with the target analyte to promote a reaction that results in a change in charge potential or current at or near the surface of the working electrode, such that an electrical signal associated with the reaction is detectable at the working electrode relative to the reference electrode to measure a parameter related to the target analyte.

13. 13. The sensor device of claim 12, wherein the chemical layer comprises a membrane including: (i) an outer layer exposed to the bodily fluid and configured to regulate permeation of reactive species including the target analyte; and (ii) an inner layer coupled between the outer layer and the surface of the working electrode to immobilize a catalyst capable of facilitating the reaction with the permeated reactive species for detection of the target analyte at the working electrode.

14. The sensor device of claim 1 , wherein the membrane comprises a thickness of less than or equal to 10 μm, or between 5 μm and 10 μm.

15. The sensor device of claim 1 , wherein the plurality of corrugations on the top surface of the outer layer comprise a height in the range of 10 μm to 20 μm.

16. 10. The sensor device of claim 1, wherein the plurality of waveforms on the top surface of the outer layer are configured to promote a functional life of the electrochemical sensor electrode assembly by increasing signal stability of the detected electrical signal and preventing fouling of the working electrode.

17. The sensor device of claim 1 , wherein the plurality of corrugations of the membrane are at least partially formed by the membrane conforming onto a three-dimensional surface of the substrate.

18. 10. The sensor device of claim 1, wherein the electronic unit further comprises a signal conditioning unit in communication with the electrochemical sensor electrode assembly via one or more electrical interface components, the signal conditioning unit comprising electrical circuitry configured to process the detected electrical signals by one or more of amplifying the electrical signals, filtering the electrical signals, or converting the electrical signals from analog to digital.

19. 20. The sensor device of claim 18, wherein the electronics unit further comprises a data processing unit in communication with the signal conditioning unit, the data processing unit comprising a processor and a memory and configured to process the electrical signals as analyte data representative of one or more parameters of the target analyte.

20. 10. The sensor device of claim 1, further comprising an electrical interconnect wire and an electrical interface contact site disposed on the substrate, the electrical interconnect wire being coupled between the electrochemical sensor electrode assembly and the electrical interface contact site.

21. 21. The sensor device of claim 20, wherein the electrical interconnect wires disposed on the substrate are sealed with a non-permeable material covering the electrical interconnect wires to provide an electrical shield from the bodily fluids.

22. 22. The sensor device of claim 21, wherein the non-permeable material comprises at least one of a parylene, a urethane, or a Teflon material.

23. 10. The sensor device of claim 1, further comprising a casing that encloses the electronic unit, the casing protecting the electronic unit from exposure to the bodily fluid and at least partially enclosing the electrochemical sensor electrode assembly such that the working electrode and the reference electrode are exposed to the bodily fluid when the sensor device is deployed within the body of the subject.

24. 24. The sensor device of claim 23, wherein the casing includes one or both of flat sides or curved sides to provide a form factor for the sensor device.

25. 24. The sensor device of claim 23, wherein the form factor of the sensor device comprises at least one of a rectangular, cylindrical, conical, elliptical, pyramidal, trapezoidal, or irregular shape.

26. 10. The sensor device of claim 1, further comprising a second electrochemical sensor electrode assembly disposed on the substrate, the second electrochemical sensor electrode assembly configured to detect a second target analyte in the bodily fluid when fully deployed within the subject's body, the second electrochemical sensor electrode assembly comprising a second working electrode and a second reference electrode associated with the second working electrode, the second working electrode functionalized with a second chemical layer configured to promote a reaction involving the second target analyte that generates a second electrical signal at the second electrochemical sensor electrode assembly.

27. 10. The sensor device of claim 1, further comprising one or more conductive pads disposed on the substrate configured to be electrically stimulated to detect a parameter associated with the bodily fluid exposed to the electrochemical sensor electrode assembly.

28. 28. The sensor device of claim 27, wherein the one or more conductive pads are capable of ensuring that the detected electrical signal is detected in a fluid-rich environment and / or reducing noise associated with the detected signal to a negligible level.

29. The sensor device of claim 1 , wherein the target analyte comprises glucose.

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