Systems and methods for analyte detection

Abstract

Devices, methods, and systems for detecting alcohol levels in an individual, such as in vivo alcohol levels in an individual.SOLUTION: The system may include an analyte sensor and a reader. The reader may receive a signal from the analyte sensor. The reader can determine blood alcohol concentration based in part on the signal received from the analyte sensor. The reader may also detect an adverse condition of the analyte sensor and / or output an indication based on the detected adverse condition.SELECTED DRAWING: Figure 1A

Description

[Technical Field]

[0001] FIELD OF THE INVENTION The subject matter described herein relates to analyte sensors and methods of use thereof. [Background technology]

[0002] Detection of various analytes can be used to aid in monitoring health conditions. Detection of analytes can be used, among other things, to determine changes in analyte levels that may indicate physiological conditions. For example, monitored glucose levels can be used by a diabetic patient to manage their glucose levels by taking appropriate action, such as administering insulin at appropriate times or consuming certain foods or beverages, based on analyte levels or trends. Other analytes may be desirable for monitoring other physiological conditions, or in some cases, multiple analytes may be used simultaneously to monitor multiple physiological conditions.

[0003] Analyte monitoring can be performed periodically or continuously over a given period of time. For continuous monitoring, one or more sensors remain at least partially implanted within the individual's tissue (e.g., cutaneously, subcutaneously, or intravenously) so that analysis can be performed in vivo. The implanted sensors can collect analyte data on demand, on a set schedule, or continuously, depending on the individual's specific health needs and / or previously measured analyte levels. For example, an in vivo enzyme-based amperometric sensor can be configured to assay one or more analytes and monitor the health of an individual. The analyte sensor can use an enzyme with specificity or sensitivity for a particular substrate. Monitored analytes can include, but are not limited to, glucose, lactate, oxygen, and ketones.

[0004] By comparison, but not by way of limitation, periodic analyte monitoring can be performed by taking samples of bodily fluids, such as blood or urine, and analyzing the samples ex vivo. While ex vivo analyte monitoring can be sufficient, there are several challenges associated with ex vivo analyte monitoring. For example, taking samples can be inconvenient or painful, and there can be an increased risk of losing data. Continuous analyte monitoring, including monitoring using sensors implanted in vivo, can overcome such challenges.

[0005] Another example of an analyte that can be monitored is alcohol. Information regarding an individual's in vivo alcohol level can be used, for example, to predict or monitor the level of another analyte of interest. For example, alcohol can alter glycemic control in an individual whose glucose levels are naturally dysregulated or lack homeostasis without intervention. Other analytes that can be dysregulated by alcohol can include triglycerides (e.g., associated with heart disease, stroke, blood pressure, obesity), gamma-glutamyltransferase (GGT) (e.g., associated with cancer, hepatitis, bone disease), and cortisol (e.g., associated with stress, inflammation). Alcohol monitoring can also be used, for example, to curb alcohol intake.

[0006] Therefore, it may be useful to continuously or periodically monitor an individual's alcohol level. Quality control measures can be used to ensure the accuracy of the monitored alcohol level. For example, there are opportunities to identify adverse sensor conditions and / or reduce or eliminate erroneous readings, including false positives and / or false negatives. Summary of the Invention

[0007] The objects and advantages of the disclosed subject matter will be set forth in and become apparent from the following description and may be learned by practice of the disclosed subject matter. Additional advantages of the disclosed subject matter may be realized and obtained by the apparatus particularly pointed out in the written description and claims, as well as from the accompanying drawings.

[0008] To improve accuracy and quality control of alcohol sensors and achieve other advantages in accordance with the objects of the disclosed subject matter, the disclosed subject matter is directed to a system including an analyte sensor and a reader including one or more processors. At least a portion of the analyte sensor is positioned in contact with a bodily fluid. The reader is configured to receive a signal from the analyte sensor. The reader is also configured to determine a blood alcohol concentration based in part on the signal received from the analyte sensor. In some examples, the reader can display the blood alcohol concentration. The reader can further detect an adverse condition of the analyte sensor. The adverse condition can include a malfunction or misalignment of the analyte sensor. A notification can be output based on the detected adverse condition. The notification can be visual, audible, or vibratory. In some examples, the reader can display the blood alcohol concentration.

[0009] As embodied herein, a method can include receiving a signal from an analyte sensor, at least a portion of which is disposed in contact with a bodily fluid. The method can also include determining a blood alcohol concentration based in part on the signal received from the analyte sensor. Additionally, the method can include detecting an adverse condition of the analyte sensor and / or outputting an indication based on the detected adverse condition of the analyte sensor. The analyte sensor can be, for example, an alcohol sensor used to detect alcohol levels, e.g., ethanol.

[0010] As embodied herein, the analyte sensor can include a temperature sensor. An adverse condition can be determined based on a temperature that drops below a threshold body temperature after a certain wearing period. In another exemplary embodiment, the analyte sensor can be a glucose sensor. An adverse condition can be based on a detected glucose level and / or a detected ethanol level.

[0011] As embodied herein, an adverse condition can be determined when the signal amplitude of the analyte sensor decreases below a background signal amplitude. In another example, a fluctuation in the background signal amplitude of the analyte sensor can be detected below a background signal fluctuation threshold over a period of time. The fluctuation can indicate an adverse condition. In yet another example, a sudden decrease in the signal amplitude of the analyte sensor can be detected.

[0012] As embodied herein, the analyte sensor is attached to an adhesive patch configured to be applied to the skin. The adhesive patch can be configured to be disabled when removed from the skin. The analyte sensor can include a proximity sensor, including a reed switch or a magnetic sensor.

[0013] As embodied herein, a temperature strip can be attached to the housing of the analyte sensor, and the temperature strip can include a temperature change above a temperature threshold. [Brief explanation of the drawings]

[0014] [Figure 1A] 1 is a system overview of a sensor applicator, a reader device, a monitoring system, a network, and a remote system. [Figure 1B] 1 is a schematic diagram illustrating the operating environment of an example analyte monitoring system for use with the technology described herein. [Figure 2A] 1 is a block diagram illustrating an example embodiment of a reader device. [Figure 2B]1 is a block diagram illustrating an example of a data receiving device for communicating with a sensor according to an exemplary embodiment of the disclosed subject matter. [Figure 2C] 1 is a block diagram illustrating an example embodiment of a sensor control device. [Figure 2D] 1 is a block diagram illustrating an example embodiment of a sensor control device. [Figure 2E] 1 is a block diagram illustrating an example of an analyte sensor according to an exemplary embodiment of the disclosed subject matter. [Figure 3A] 10A-10C are proximal perspective views illustrating an example embodiment of a user preparing a tray for assembly. [Figure 3B] 10A-10C are side views illustrating an example embodiment of a user preparing an applicator device for assembly. [Figure 3C] 10A-10C are proximal perspective views illustrating an example embodiment of a user inserting an applicator device into a tray during assembly. [Figure 3D] 10A-10C are proximal perspective views illustrating an example embodiment of a user removing the applicator device from the tray during assembly. [Figure 3E] 1A-1C are proximal perspective views illustrating an example embodiment of a patient applying a sensor with an applicator device. [Figure 3F] 1A and 1B are proximal perspective views showing an example embodiment of a patient with an applied sensor and a used applicator device. [Figure 4A] 1A and 1B are side views illustrating an example embodiment of an applicator device coupled with a cap. [Figure 4B] 1 is a side perspective view of an example embodiment of an applicator device and cap separated. FIG. [Figure 4C] 1 is a perspective view illustrating an example embodiment of an applicator device and a distal end of an electronics housing. [Figure 4D] FIG. 1 is a top perspective view of an exemplary applicator device in accordance with the disclosed subject matter. [Figure 4E] FIG. 4E is a bottom perspective view of the applicator device of FIG. 4D. [Figure 4F] FIG. 4E is an exploded view of the applicator device of FIG. 4D. [Figure 4G] FIG. 4E is a side cross-sectional view of the applicator device of FIG. 4D. [Figure 5] FIG. 10 is a proximal perspective view showing an example embodiment of a tray with an associated sterilization lid. [Figure 6A] 10A-10C are proximal perspective cross-sectional views illustrating an example embodiment of a tray with a sensor delivery component. [Figure 6B] FIG. 13 is a proximal perspective view showing the sensor delivery component. [Figure 7A] FIG. 1 illustrates an isometric exploded top view of an exemplary sensor control device. [Figure 7B] FIG. 2 is an isometric exploded bottom view of an exemplary sensor control device. [Figure 8A] 1A and 1B are assembly and cross-sectional views of an on-body device including an integrated connector for sensor assembly. [Figure 8B] 1A and 1B are assembly and cross-sectional views of an on-body device including an integrated connector for sensor assembly. [Figure 8C] 1A and 1B are assembly and cross-sectional views of an on-body device including an integrated connector for sensor assembly. [Figure 9A] 2D is a side view of an example embodiment of the sensor applicator of FIG. 1A coupled with the cap of FIG. 2C. [Figure 9B] 2D is a side cross-sectional view of an example embodiment of the sensor applicator of FIG. 1A coupled with the cap of FIG. 2C. [Figure 10A] FIG. 10 is an isometric view of another example sensor control device. [Figure 10B] FIG. 10 is a side view of another example of a sensor control device. [Figure 11A] 10A-10B are side cross-sectional views illustrating the assembly of a sensor applicator having the sensor control device of FIGS. [Figure 11B] 10A-10B are side cross-sectional views illustrating the assembly of a sensor applicator having the sensor control device of FIGS. [Figure 11C] 10A-10B are side cross-sectional views illustrating the assembly of a sensor applicator having the sensor control device of FIGS. [Figure 12A]10A-10B are side cross-sectional views illustrating the assembly and disassembly of an example embodiment of a sensor applicator having the sensor control device of FIGS. [Figure 12B] 10A-10B are side cross-sectional views illustrating the assembly and disassembly of an example embodiment of a sensor applicator having the sensor control device of FIGS. [Figure 12C] 10A-10B are side cross-sectional views illustrating the assembly and disassembly of an example embodiment of a sensor applicator having the sensor control device of FIGS. [Figure 13A] 1A-1C show cross-sectional views illustrating an example embodiment of an applicator during a placement stage. [Figure 13B] 1A-1C show cross-sectional views illustrating an example embodiment of an applicator during a placement stage. [Figure 13C] 1A-1C show cross-sectional views illustrating an example embodiment of an applicator during a placement stage. [Figure 13D] 1A-1C show cross-sectional views illustrating an example embodiment of an applicator during a placement stage. [Figure 13E] 1A-1C show cross-sectional views illustrating an example embodiment of an applicator during a placement stage. [Figure 13F] 1A-1C show cross-sectional views illustrating an example embodiment of an applicator during a placement stage. [Figure 14] 1 is a graph showing an example of the in vitro sensitivity of an analyte sensor. [Figure 15] 1 is a diagram illustrating an example of an operational state of a sensor according to an exemplary embodiment of the disclosed subject matter. [Figure 16] 1 is a diagram illustrating an example of the operations and data flow for over-the-air programming of a sensor in accordance with the disclosed subject matter. [Figure 17] 1 is a diagram illustrating an example of data flow for secure exchange of data between two devices in accordance with the disclosed subject matter. [Figure 18A] 1 is a cross-sectional schematic diagram illustrating an exemplary analyte sensor including a single active area as embodied herein. [Figure 18B] 1 is a cross-sectional schematic diagram illustrating an exemplary analyte sensor including a single active area as embodied herein. [Figure 18C]1 is a cross-sectional schematic diagram illustrating an exemplary analyte sensor including a single active area as embodied herein. [Figure 19] 1 is a cross-sectional schematic diagram illustrating an exemplary analyte sensor including two active regions as embodied herein. [Figure 20] 1 is a cross-sectional schematic diagram illustrating an exemplary analyte sensor including two active regions as embodied herein. [Figure 21] 1 is a graph illustrating the current output of an exemplary analyte sensor embodied herein. [Figure 22A] 1 is a graph illustrating the background signal of an exemplary analyte sensor embodied herein. [Figure 22B] 1 is a graph illustrating the background signal of an exemplary analyte sensor embodied herein. [Figure 22C] 1 is a graph illustrating the background signal of an exemplary analyte sensor embodied herein. [Figure 22D] 1 is a graph illustrating the background signal of an exemplary analyte sensor embodied herein. DETAILED DESCRIPTION OF THE INVENTION

[0015] Before describing the present subject matter in detail, it is to be understood that this disclosure is not limited to particular embodiments described, as such may, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting, since the scope of the present disclosure will be limited only by the appended claims.

[0016] As used in this specification and the appended claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise.

[0017] The publications discussed herein are provided solely for their disclosure prior to the filing date of the present application. Nothing herein should be construed as an admission that the present disclosure is not entitled to antedate such publication by virtue of prior disclosure. Further, the publication dates provided may be different from the actual publication dates, which may need to be independently confirmed.

[0018] In general, embodiments of the present disclosure include systems, devices, and methods for the use of an analyte sensor insertion applicator for use with an in-vivo analyte monitoring system. The applicator may be provided to a user in a sterile package with the electronics housing of the sensor control unit housed therein. According to some embodiments, a structure separate from the applicator, such as a container, may also be provided to a user in a sterile package with the sensor module and tip module contained therein. The user can connect the sensor module to the electronics housing and connect the tip to the applicator in an assembly process that includes inserting the applicator into the container in a specified manner. In other embodiments, the applicator, sensor control unit, sensor module, and tip module may be provided in a single package. The applicator can be used to position the sensor control unit on the human body to contact the sensor with the wearer's bodily fluids. The embodiments provided herein are improvements that reduce the likelihood of the sensor being improperly inserted or damaged, or eliciting an adverse physiological response. Other improvements and advantages are also provided. Various configurations of these devices are described in detail by way of example embodiments only.

[0019] Additionally, many embodiments include an in vivo analyte sensor that is structurally configured such that at least a portion of the sensor is located or can be located within a user's body to obtain information regarding at least one analyte in the body. However, it should be noted that the embodiments disclosed herein may be used with in vivo analyte monitoring systems that incorporate in vitro capabilities, as well as solely in vitro or ex vivo analyte monitoring systems, including systems that are completely non-invasive.

[0020] Furthermore, for any and all embodiments of the methods disclosed herein, systems and devices capable of performing each of those embodiments are encompassed within the scope of the present disclosure. For example, sensor control device embodiments are disclosed, and these devices may have one or more sensors, analyte monitoring circuitry (e.g., analog circuitry), memory (e.g., for storing instructions), power sources, communication circuitry, transmitters, receivers, processors, and / or controllers (e.g., for executing instructions) that can perform or facilitate the performance of any method step. These sensor control device embodiments may be used, or may be capable of being used, to perform steps performed by the sensor control device from any method described herein.

[0021] Additionally, the systems and methods presented herein can be used for the operation of sensors used in analyte monitoring systems, such as, but not limited to, wellness, fitness, diet, research, information, or any purpose involving analyte detection over time. As used herein, "analyte sensor" or "sensor" can mean, for purposes of explanation and without limitation, any device capable of receiving sensor information from a user, including a temperature sensor, a blood pressure sensor, a pulse or heart rate sensor, a glucose level sensor, an analyte sensor, a physical activity sensor, a body movement sensor, or any other sensor for gathering physical or biological information. Analytes measured by the analyte sensor may include, by way of example and not limitation, glucose, ketones, lactate, oxygen, hemoglobin A1C, albumin, alcohol, alkaline phosphatase, alanine transaminase, aspartate aminotransferase, bilirubin, blood urea nitrogen, calcium, carbon dioxide, chloride, creatinine, hematocrit, lactate, magnesium, oxygen, pH, phosphorus, potassium, sodium, total protein, uric acid, and the like.

[0022] As mentioned above, several embodiments of systems, devices, and methods are described herein that provide improved assembly and use of a skin sensor insertion device for use with an in vivo analyte monitoring system. In particular, several embodiments of the present disclosure are designed to improve sensor insertion methods for in vivo analyte monitoring systems, and particularly to prevent premature retraction of the insertion tip during the sensor insertion process. For example, some embodiments include a skin sensor insertion mechanism with an increased firing rate and slower tip retraction. In other embodiments, the tip retraction mechanism may be actuated by motion so that the tip is not retracted until the user pulls the applicator away from the skin. As a result, these embodiments may reduce the likelihood of premature retraction of the insertion tip during the sensor insertion process, reduce the likelihood of improper sensor insertion, and reduce the likelihood of sensor damage during the sensor insertion process, to name a few advantages. Some embodiments of the present disclosure also provide an improved insertion tip module that accounts for the small-scale skin sensors and the relatively shallow insertion path present in the subject's dermis layer. Additionally, some embodiments of the present disclosure are designed to prevent undesired axial and / or rotational movement of the applicator components during sensor insertion. These embodiments can therefore reduce the likelihood of capillary disruption, which can lead to instability of the placed skin sensor, irritation at the insertion site, damage to surrounding tissue, and blood contamination of skin fluids, to name a few advantages. Additionally, to mitigate inaccurate sensor readings that may be caused by trauma at the insertion site, some embodiments of the present disclosure can reduce the depth of needle end penetration relative to the sensor tip during insertion.

[0023] However, before describing these aspects of the embodiments in detail, it is desirable to first describe examples of devices that may be present, for example, in an in vivo analyte monitoring system, and examples of their operation, all of which may be used in conjunction with the embodiments described herein.

[0024] There are various types of in-vivo analyte monitoring systems. A "continuous analyte monitoring" system (or "continuous glucose monitoring" system), for example, may transmit data from a sensor controller to a reader device continuously and without prompting, e.g., automatically according to a schedule. A "flash analyte monitoring" system (or "flash glucose monitoring" system or simply "flash" system), as another example, may transmit data from the sensor controller in response to a scan or request for data by a reader device, e.g., via near field communication (NFC) or radio frequency identification (RFID) protocols. In-vivo analyte monitoring systems may also operate without the need for fingerstick calibration.

[0025] In vivo analyte monitoring systems can be distinguished from "in vitro" systems that contact a biological sample outside the body (i.e., "ex vivo") and generally include a measurement device having a port that accepts an analyte test strip that carries a bodily fluid that can be analyzed to determine a user's blood glucose level.

[0026] An in-vivo monitoring system may include a sensor that contacts a user's bodily fluids while positioned in vivo and detects the analyte level therein. The sensor may be part of a sensor control device that resides on the user's body and includes electronics and a power source that enable and control analyte detection. Sensor control devices and variations thereof may also be referred to as "sensor control units," "on-body electronics" devices or units, "on-body" devices or units, or "sensor data communications" devices or units, to name a few.

[0027] In-vivo monitoring systems may also include devices that receive sensed analyte data from the sensor control device and process and / or display the sensed analyte data to a user in any number of forms. These devices and variations thereof may be referred to as "handheld reader devices," "reader devices" (or simply "readers"), "handheld electronic devices" (or simply "handhelds"), "portable data processing" devices or units, "data receivers," "receiver" devices or units (or simply "receivers"), or "remote" devices or units, to name a few. Other devices, such as personal computers, are also utilized with or incorporated into in-vivo and in-vitro monitoring systems.

[0028] FIG. 1A is a conceptual diagram illustrating an example embodiment of an analyte monitoring system 100 including a sensor applicator 150, a sensor control device 102, and a reader device 120. Here, the sensor applicator 150 can be used to deliver the sensor control device 102 to a monitoring location on a user's skin, with the sensor 110 held in place for a period of time by an adhesive patch 105. The sensor control device 102, further described in FIGS. 2B and 2C, can communicate with the reader device 120 via a communication path 140 using wired or wireless technology. Examples of wireless protocols include Bluetooth®, Bluetooth® Low Energy (BLE, BTLE, Bluetooth® SMART, etc.), Near Field Communication (NFC), etc. A user can monitor applications installed in memory on the reader device 120 using a screen 122, and the input 121 and device battery can be recharged using a power port 123. Further details regarding the reader device 120 are described below with respect to FIG. 2A. The reader device 120 can communicate with the local computer system 170 via communication path 141 using wired or wireless technology. The local computer system 170 can include one or more of a laptop, desktop, tablet, phablet, smartphone, set-top box, video game console, or other computing device, and the wireless communication can include any of several applicable wireless network protocols, including Bluetooth®, Bluetooth® Low Energy (BTLE), Wi-Fi, or others. The local computer system 170 can communicate with the network 190 via communication path 143, similar to how the reader device 120 can communicate with the network 190 via communication path 142, using the wired or wireless technology previously described. The network 190 can be any of private and public networks, local or wide area networks, or some other network.Trusted computer system 180 may include a server, provide authentication services and secure data storage, and communicate with network 190 via communication path 144 using wired or wireless technology.

[0029] FIG. 1B illustrates the operating environment of an analyte monitoring system 100a that can embody the technology described herein. The analyte monitoring system 100a can include a system of components designed to provide monitoring of a parameter, such as an analyte level, in a human or animal body, or provide other operations based on the configuration of various components. As embodied herein, the system can include a low-power analyte sensor 110, or simply a “sensor,” worn by a user or attached to the body from which information is being collected. As embodied herein, the analyte sensor 110 can be a sealed, disposable device with a predetermined active use life (e.g., 1 day, 14 days, 30 days, etc.). The sensor 110 can be attached to the skin of a user's body and can be designed to remain adhered for the duration of the sensor's life or to remain functional when selectively detached and reattached. The low-power analyte monitoring system 100a may further include a data receiving device 120 or a multi-purpose data receiving device 130 configured as described herein to facilitate retrieval and delivery of data, including analyte data, from the analyte sensor 110.

[0030] As embodied herein, analyte monitoring system 100a may include software or firmware libraries or applications provided to a third party, for example, via remote application server 150 or application storefront server 160, and embedded in a multipurpose hardware device 130, such as a mobile phone, tablet, personal computing device, or other similar computing device capable of communicating with analyte sensor 110 via a communications link. Multipurpose hardware may further include embedded devices, including, but not limited to, insulin pumps or insulin pens, having embedded libraries configured to communicate with analyte sensor 110. While the illustrated embodiment of analyte monitoring system 100a includes only one of each of the illustrated devices, the present disclosure contemplates that analyte monitoring system 100a may incorporate multiple components of each that interact throughout the system. For example, but not limited to, as embodied herein, data receiving device 120 and / or multipurpose data receiving device 130 may include multiple components of each. As embodied herein, the multiplexed data receiving device 130 may communicate directly with the sensors 110 described herein. Additionally or alternatively, the data receiving device 130 may communicate with a secondary data receiving device 130 to provide analyte data or data visualization or analysis for secondary display to a user or other authorized party.

[0031] 2A is a block diagram illustrating an example embodiment of a reader device configured as a smartphone. Here, reader device 120 may include display 122, input component 121, and processing core 206 including communication processor 222 connected to memory 223 and application processor 224 connected to memory 225. Separate memory 230, RF transceiver 228 with antenna 229, and power supply 226 with power management module 238 may also be included. A multi-function transceiver 232 may further be included, which may communicate with antenna 234 via Wi-Fi, NFC, Bluetooth, BTLE, and GPS. As will be appreciated by those skilled in the art, these components are electrically and communicatively connected in a manner to create a functional device.

[0032] For purposes of illustration and not limitation, reference is made to an exemplary embodiment of a data receiving device 120 for use with the disclosed subject matter shown in FIG. 2B. The data receiving device 120 and associated multi-purpose data receiving device 130 include components germane to the discussion of the analyte sensor 110 and its operation, and additional components may be included. In certain embodiments, the data receiving device 120 and multi-purpose data receiving device 130 may be or include components provided by third parties, and are not necessarily limited to including devices made by the same manufacturer as the sensor 110.

[0033] 2B , the data receiving device 120 includes an ASIC 4000 that includes a microcontroller 4010, memory 4020, and storage 4030, and is communicatively connected to a communication module 4040. Power for the components of the data receiving device 120 may be delivered by a power module 4050, which may include a rechargeable battery as embodied herein. The data receiving device 120 may further include a display 4070 to facilitate review of analyte data received from the analyte sensor 110 or other devices (e.g., the user device 140 or the remote application server 150). The data receiving device 120 may include separate user interface components (e.g., a physical key, a light sensor, a microphone, etc.).

[0034] The communications module 4040 may include a BLE module 4041 and an NFC module 4042. The data receiving device 120 may be configured to wirelessly connect to the analyte sensor 110, send commands to the analyte sensor 110, and receive data from the analyte sensor 110. As embodied herein, the data receiving device 120 may be configured to operate as an NFC scanner and a BLE endpoint via a particular module of the communications module 4040 (e.g., the BLE module 4042 or the NFC module 4043) with respect to the analyte sensor 110 described herein. For example, the data receiving device 120 may use a first module of the communications module 4040 to issue commands (e.g., an activation command for the sensor's data broadcast mode, a pairing command for identifying the data receiving device 120) to the analyte sensor 110 and use a second module of the communications module 4040 to receive data from and send data to the analyte sensor 110. The data receiving device 120 may be configured to communicate with the user device 140 via a universal serial bus (USB) module 4045 of the communication module 4040 .

[0035] As another example, the communication module 4040 may include, for example, a cellular radio module 4044. The cellular radio module 4044 may include one or more radio transceivers for communicating using broadband cellular networks, including but not limited to third-generation (3G), fourth-generation (4G), and fifth-generation (5G) networks. Furthermore, the communication module 4040 of the data receiving device 120 may include a Wi-Fi radio module 4043 for communicating using wireless local area networks according to one or more of the IEEE 802.11 standards (e.g., 802.11a, 802.11b, 802.11g, 802.11n (also known as Wi-Fi 4), 802.11ac (also known as Wi-Fi 5), and 802.11ax (also known as Wi-Fi 6)). Using the cellular radio module 4044 or the Wi-Fi radio module 4043, the data receiving device 120 may communicate with the remote application server 150 to receive analyte data or provide updates or input received from a user (e.g., via one or more user interfaces). Although not shown, the communication module 5040 of the analyte sensor 120 may similarly include a cellular radio module or a Wi-Fi radio module.

[0036] As embodied herein, the onboard storage 4030 of the data receiving device 120 may store analyte data received from the analyte sensor 110. Additionally, the data receiving device 120, the multi-purpose data receiving device 130, or the user device 140 may be configured to communicate with a remote application server 150 over a wide area network. As embodied herein, the analyte sensor 110 may provide data to the data receiving device 120 or the multi-purpose data receiving device 130. The data receiving device 120 may transmit the data to the user computing device 140. The user computing device 140 (or the multi-purpose data receiving device 130) may then transmit the data to the remote application server 150 for processing and analysis.

[0037] As embodied herein, the data receiving device 120 may further include sensing hardware 4060 similar to or extended from the sensing hardware 5060 of the analyte sensor 110. In particular embodiments, the data receiving device 120 may be configured to interface with the analyte sensor 110 and act based on analyte data received from the analyte sensor 110. By way of example, if the analyte sensor 110 is a glucose sensor, the data receiving device 120 may be or include an insulin pump or an insulin injection pen. In conjunction, the compatible device 130 may adjust insulin dosage for the user based on the glucose value received from the analyte sensor.

[0038] 2C and 2D are schematic block diagrams illustrating an example embodiment of a sensor controller 102 having an analyte sensor 110 and sensor electronics 160 (including analyte monitoring circuitry), which may have most of the processing power for rendering final result data suitable for display to a user. In FIG. 2C, a single semiconductor chip 161 is shown, which may be a custom application-specific integrated circuit (ASIC). Within the ASIC 161, certain high-level functional units are shown, including an analog front-end (AFE) 162, a power management (or control) circuit 164, a processor 166, and a communications circuit 168 (which may be implemented as a transmitter, receiver, transceiver, passive circuitry, or in other ways according to a communications protocol). In this embodiment, both the AFE 162 and the processor 166 are used as analyte monitoring circuitry, although in other embodiments, either circuitry may perform the analyte monitoring function. The processor 166 may include one or more processors, microprocessors, controllers, and / or microcontrollers, each of which may be a separate chip or distributed among (and portions of) multiple different chips.

[0039] Memory 163 is also included in ASIC 161 and may be shared by the various functional units present in ASIC 161 or distributed among two or more of them. Memory 163 may also be a separate chip. Memory 163 may be volatile and / or non-volatile memory. In this embodiment, ASIC 161 is connected to a power source 170, which may be a button cell battery or the like. AFE 162 interfaces with and receives measurement data from in-vivo analyte sensor 110 and outputs the data in digital form to processor 166, which then processes the data to arrive at final result glucose discrete values ​​and trend values, etc. This data may then be provided to communication circuitry 168 for transmission via antenna 171 to reader device 120 (not shown), where minimal further processing by a resident software application is required to display the data, for example.

[0040] FIG. 2D is similar to FIG. 2C but instead includes two discrete semiconductor chips 162 and 174, which may be packaged together or separately. Here, AFE 162 resides on ASIC 161. Processor 166 is integrated with power management circuitry 164 and communications circuitry 168 on chip 174. AFE 162 includes memory 163, and chip 174 includes memory 165, which may be separate or distributed therein. In one exemplary embodiment, AFE 162 is combined with power management circuitry 164 and processor 166 on one chip, and communications circuitry 168 is on a separate chip. In another exemplary embodiment, both AFE 162 and communications circuitry 168 are on one chip, and processor 166 and power management circuitry 164 are on another chip. Note that other chip combinations are possible, including three or more chips, each performing the distinct functions described or sharing one or more functions for fail-safe redundancy.

[0041] For purposes of illustration and not limitation, reference is made to an exemplary embodiment of an analyte sensor 110 for use in accordance with the disclosed subject matter shown in Figure 2E. Figure 2E shows a block diagram of an example analyte sensor 110 in accordance with an exemplary embodiment that is compatible with the security architecture and communication schemes described herein.

[0042] As embodied herein, the analyte sensor 110 may include an application specific integrated circuit ("ASIC") 5000 communicatively coupled to a communications module 5040. The ASIC 5000 may include a microcontroller core 5010, an on-board memory 5020, and a storage memory 5030. The storage memory 5030 may store data used in the authentication and encryption security architecture. The storage memory 5030 may store programming instructions for the sensor 110. As embodied herein, a specific communications chipset may be incorporated into the ASIC 5000 (e.g., an NFC transceiver 5025). The ASIC 5000 may receive power from a power module 5050, such as an on-board battery, or from NFC pulses. The storage memory 5030 of the ASIC 5000 may be programmed to include information such as an identifier for the sensor 110 for identification and tracking purposes. The storage memory 5030 may also be programmed with configuration or calibration parameters for use by the sensor 110 and its various components. The storage memory 5030 may include rewritable or one-time programming (OTP) memory that can be updated using techniques described herein to extend the usefulness of the sensor 110.

[0043] As embodied herein, the communications module 5040 of the sensor 100 may be or include one or more modules that assist the analyte sensor 110 in communicating with other devices in the analyte monitoring system 100. By way of example only and not limitation, an example communications module 5040 may include a Bluetooth® Low Energy (“BLE”) module 5041. As used throughout this disclosure, Bluetooth® Low Energy (“BLE”) refers to a short-range communications protocol optimized to simplify pairing of Bluetooth® devices for end users. The communications module 5040 can send and receive data and commands via interaction with a similarly capable communications module in the data receiving device 120 or user device 140. The communications module 5040 may include additional or alternative chipsets for use with personal area networks according to the IEEE 802.15 protocol, IEEE 802.11 protocol, infrared communications according to the Infrared Data Association standard (IrDA), or other similar short-range communications schemes.

[0044] To perform its functionality, sensor 100 may further include suitable sensing hardware 5060 appropriate for that function. As embodied herein, sensing hardware 5060 may include an analyte sensor that is placed transcutaneously or subcutaneously in contact with the subject's bodily fluid. The analyte sensor may generate sensor data that includes a value corresponding to the level of one or more analytes in the bodily fluid.

[0045] The components of the sensor control device 102 may be acquired by the user in multiple packages that require final assembly by the user before delivery to the appropriate user location. Figures 3A-3D show an example embodiment of a user assembly process for the sensor control device 102, including preparation of the separate components before joining the components to prepare the sensor for delivery. Figures 3E-3F show an example embodiment of delivering the sensor control device 102 to the appropriate user location by selecting the appropriate delivery location and orienting the device 102 to that location.

[0046] 3A is a proximal perspective view illustrating an example embodiment of a user preparing a container 810, configured herein as a tray (although other packaging may be used), for the assembly process. The user may accomplish this preparation by, for example, removing the lid 812 from the tray 810 by peeling the non-adhesive portion of the lid 812 from the tray 810 such that the adhesive portion of the lid 812 is removed, exposing the platform 808. Removal of the lid 812 may be suitable in various embodiments, so long as the platform 808 is properly exposed in the tray 810. The lid 812 may then be set aside.

[0047] 3B is a side view illustrating an example embodiment of a user preparing applicator device 150 for assembly. Applicator device 150 may be provided in a sterile package sealed by cap 708. Preparing applicator device 150 may include removing housing 702 from cap 708 to expose sheath 704 (FIG. 3C). This may be accomplished by unscrewing (or otherwise removing) cap 708 from housing 702. Cap 708 may then be set aside.

[0048] 3C is a proximal perspective view showing an example embodiment of a user inserting applicator device 150 into tray 810 during assembly. First, a user can align housing orientation feature 1302 (or slot or recess) and tray orientation feature 924 (abutment or detent) before inserting sheath 704 into platform 808 inside tray 810. Inserting sheath 704 into platform 808 temporarily unlocks sheath 704 from housing 702, and platform 808 from tray 810. At this stage, removal of applicator device 150 from tray 810 will result in the same condition as before the initial insertion of applicator device 150 into tray 810 (i.e., the process can be reversed or interrupted at this point and then repeated without consequence).

[0049] While the housing 702 is advanced distally, the sheath 704 is maintained in position within the platform 808 relative to the housing 702 and couples with the platform 808, advancing the platform 808 distally relative to the tray 810. This process unlocks and folds the platform 808 within the tray 810. The sheath 704 contacts and disengages a locking feature (not shown) within the tray 810 that prevents the sheath 704 from moving (relatively) while the housing 702 continues to advance the platform 808 distally. When the advancement of the housing 702 and platform 808 is complete, the sheath 704 is permanently unlocked from the housing 702. A tip and sensor (not shown) within the tray 810 may couple with an electronics housing (not shown) within the housing 702 upon completion of distal advancement of the housing 702. The operation and interaction of applicator device 150 and tray 810 is further described below.

[0050] 3D is a proximal perspective view illustrating an example embodiment in which a user removes applicator device 150 from tray 810 during assembly. A user can remove applicator 150 from tray 810 by advancing housing 702 proximally relative to tray 810 or by other action that has the same end effect as uncoupling applicator 150 from tray 810. Applicator device 150 is removed with sensor control device 102 (not shown) fully assembled therein (tip, sensor, electronics) and positioned for delivery.

[0051] 3E is a proximal perspective view illustrating an example embodiment in which a patient uses applicator device 150 to apply sensor control unit 102 to a target area of ​​skin, such as the abdomen or other suitable location. Distal advancement of housing 702 collapses sheath 704 into housing 702, applying the sensor to the target location such that the adhesive layer on the bottom side of sensor control unit 102 adheres to the skin. When housing 702 is fully advanced, the tip is automatically retracted, while the sensor (not shown) is left in place to measure the analyte level.

[0052] 3F is a proximal perspective view of an example patient embodiment with the sensor control unit 102 in the application position. The user can then remove the applicator 150 from the application site.

[0053] 3A-3F and elsewhere herein, system 100 may reduce or eliminate the possibility of accidental breakage, permanent deformation, or incorrect assembly of applicator components compared to prior art systems. Because applicator housing 702 directly engages platform 808 while sheath 704 unlocks, rather than indirect engagement through sheath 704, the relative angle between sheath 704 and housing 702 does not result in breakage or permanent deformation of arms or other components. The likelihood of relatively large forces (as in conventional devices) during assembly is reduced, which in turn reduces the likelihood of user assembly failure.

[0054] Figure 4A is a side view of an example embodiment of applicator device 150 coupled with screw cap 708. This is an example of how applicator 150 may be shipped and received by a user before being assembled with a sensor by the user. Figure 4B is a side perspective view showing applicator 150 and cap 708 after they have been separated. Figure 4C is a perspective view of an example embodiment of the distal end of applicator device 150 with electronics housing 706 and adhesive patch 105 removed from their positions within sensor carrier 710 of sheath 704 while cap 708 is in place.

[0055] 4D-4G, for purposes of illustration and not limitation, the applicator device 20150 may be provided to a user as a single, integrated assembly. Figures 4D and 4E provide top and bottom perspective views, respectively, of the applicator device 20150, Figure 4F provides an exploded view of the applicator device 20150, and Figure 4G provides a side cross-sectional view. The perspective view illustrates how the applicator 20150 is shipped and received by a user. The exploded and cross-sectional views illustrate the components of the applicator device 20150. The applicator device 20150 may include a housing 20702, a gasket 20701, a sheath 20704, a sharps carrier 201102, a spring 205612, a sensor carrier 20710 (also called a "puck carrier"), a sharps hub 205014, a sensor control device (also called a "puck") 20102, an adhesive patch 20105, a desiccant 20502, a cap 20708, a serial label 20709, and a tamper evidence feature 20712. When received by a user, only the housing 20702, the cap 20708, the tamper evidence feature 20712, and the label 20709 are visible. Tamper evidence feature 20712 may be, for example, a sticker coupled to each of housing 20702 and cap 20708, such that tamper evidence feature 20712 can be irreparably damaged by, for example, disconnecting housing 20702 from cap 20708, thereby indicating to a user that housing 20702 has previously been disconnected from cap 20708. These features are described in more detail below.

[0056] FIG. 5 is a proximal perspective view showing an example embodiment of a tray 810 with a sterilization lid 812 removably coupled thereto, which may illustrate how the package may be shipped and received by a user prior to assembly.

[0057] 6A is a proximal perspective cross-sectional view showing the sensor delivery components within the tray 810. The platform 808 is slidably coupled within the tray 810. The desiccant 502 is fixed relative to the tray 810. The sensor module 504 is mounted within the tray 810.

[0058] 6B is a proximal perspective view showing the sensor module 504 in more detail, where the retention arm extension 1834 of the platform 808 releasably secures the sensor module 504 in place. The module 2200 is coupled to the connector 2300, the tip module 2500, and the sensor (not shown) so that they can be removed together as the sensor module 504 during assembly.

[0059] 1 and 3A-3G, in a two-piece architecture system, the sensor tray 202 and the sensor applicator 102 are provided to the user as separate packages, thus requiring the user to open each package and ultimately assemble the system. In some applications, the separately sealed packages allow the sensor tray 202 and the sensor applicator 102 to be sterilized by separate sterilization processes that are specific to the contents of each package and are not otherwise compatible with the contents of the other package. More specifically, the sensor tray 202, including the plug assembly 207, including the sensors 110 and tips 220, can be sterilized using radiation sterilization, such as electron beam (i.e., "e-beam") irradiation. Suitable radiation sterilization processes include, but are not limited to, electron beam (e-beam) irradiation, gamma irradiation, X-ray irradiation, or any combination thereof. However, radiation sterilization may damage electrical components located within the electronics housing of the sensor control device 102. Therefore, if the sensor applicator 102, including the electronics housing of the sensor control device 102, needs to be sterilized, it can be sterilized by another method, such as gas chemical sterilization using ethylene oxide. However, gas chemical sterilization may damage enzymes or other chemical and biological materials contained in the sensors 110. Because of this sterilization incompatibility, the sensor tray 202 and the sensor applicator 102 are typically sterilized in separate sterilization processes and then packaged separately, which requires the user to perform final assembly of the parts for use.

[0060] 7A and 7B are top and bottom exploded views, respectively, of a sensor control device 3702 in accordance with one or more embodiments. The shell 3706 and mount 3708 operate as opposing clamshell halves that contain or otherwise substantially encapsulate the various electronic components of the sensor control device 3702. As shown, the sensor control device 3702 may include a printed circuit board assembly (PCBA) 3802 that includes a printed circuit board (PCB) 3804 to which multiple electronic modules 3806 are connected. Examples of electronic modules 3806 include, but are not limited to, resistors, transistors, capacitors, inductors, diodes, and switches. Conventional sensor control devices typically stack PCB components on only one side of the PCB. In contrast, the PCB components 3806 in the sensor control device 3702 may be distributed across both surface areas (i.e., the top and bottom) of the PCB 3804.

[0061] In addition to the electronics module 3806, the PCBA 3802 may also include a data processing unit 3808 mounted on the PCB 3804. The data processing unit 3808 may comprise, for example, an application specific integrated circuit (ASIC) configured to perform one or more functions or routines associated with the operation of the sensor control device 3702. More specifically, the data processing unit 3808 may be configured to perform data processing functions, which may include, but are not limited to, filtering and encoding data signals, each of which corresponds to a user's sampled analyte level. The data processing unit 3808 may also include an antenna for communicating with or otherwise communicating with the reader device 106 (FIG. 1).

[0062] A battery aperture 3810 may be defined in the PCB 3804 and sized to receive and seat a battery 3812 configured to power the sensor controller 3702. An axial battery contact 3814a and a radial battery contact 3814b may extend into the battery aperture 3810 to couple to the PCB 3804 and facilitate the delivery of power from the battery 3812 to the PCB 3804. As their names suggest, the axial battery contact 3814a may be configured to provide an axial contact for the battery 3812, while the radial battery contact 3814b may provide a radial contact for the battery 3812. Locating the battery 3812 within the battery aperture 3810 with the battery contacts 3814a,b helps to reduce the height H of the sensor controller 3702, which allows the PCB 3804 to be centrally located and its components to be distributed on both sides (i.e., top and bottom). This also helps make it easier to mount the chamfer 3718 onto the electronics housing 3704 .

[0063] The sensor 3716 may be centrally disposed relative to the PCB 3804 and may include a tail 3816, a flag 3818, and a neck 3820 interconnecting the tail 3816 and the flag 3818. The tail 3816 may be configured to extend through a central aperture 3720 of the mount 3708 that is received transcutaneously beneath the skin of a user. Additionally, the tail 3816 may have an enzyme or other chemical contained therein that helps facilitate monitoring of the analyte.

[0064] The flag 3818 may include a generally flat surface having one or more sensor contacts 3822 (three shown in FIG. 7B ) disposed thereon. The sensor contacts 3822 may be configured to align with and engage one or more corresponding circuit contacts 3824 (three shown in FIG. 7A ) provided on the PCB 3804. In some embodiments, the sensor contacts 3822 may comprise a carbon-impregnated polymer printed or otherwise digitally applied to the flag 3818. Conventional sensor control devices generally include a connector made from silicone rubber encapsulating one or more compliant carbon-impregnated polymer modules that serve as conductive contacts between the sensor and the PCB. In contrast, the sensor contacts 3822 of the present disclosure provide a direct connection between the sensor 3716 and the PCB 3804 connection, which eliminates the need for prior art connectors and advantageously reduces the height H. Furthermore, the elimination of the compliant carbon-impregnated polymer modules eliminates significant circuit resistance, thus improving circuit conductivity.

[0065] The sensor control device 3702 may further include a compliant member 3826 that may be disposed between the flag 3818 and the inner surface of the shell 3706. More specifically, when the shell 3706 and the mount 3708 are assembled together, the compliant member 3826 may be configured to provide a passive biasing load to the flag 3818 that urges the sensor contacts 3822 into continuous engagement with the corresponding circuit contacts 3824. In the illustrated embodiment, the compliant member 3826 is an elastomeric O-ring, but may instead comprise any other type of biasing device or mechanism, such as a compression spring, without departing from the scope of the present disclosure.

[0066] The sensor control device 3702 may further include one or more electromagnetic shields, shown as a first shield 3828a and a second shield. The shell 3706 may include or otherwise define a first clocking receptacle 3830a (FIG. 7B) and a second clocking receptacle 3830b (FIG. 7B), and the mount 3708 may include or otherwise define a first clocking post 3832a (FIG. 7A) and a second clocking post 3832b (FIG. 7A). The shell 3706 is properly aligned with the mount 3708 by mating the first and second clocking receptacles 3830a,b with the first and second clocking posts 3832a,b, respectively.

[0067] 7A , the inner surface of the mount 3708 may include or otherwise define a number of pockets or recesses configured to accommodate various components of the sensor control unit 3702 when the shell 3706 is mated to the mount 3708. For example, the inner surface of the mount 3708 may define a battery locator 3834 configured to accommodate a portion of the battery 3812 when the sensor control unit 3702 is assembled. An adjacent contact pocket 3836 may be configured to accommodate a portion of the axial contact 3814a.

[0068] Additionally, a plurality of module pockets 3838 may be defined on the inner surface of the mount 3708 to accommodate various electronic modules 3806 disposed on the bottom of the PCB 3804. Additionally, a shield locator 3840 may be defined on the inner surface of the mount 3708 to accommodate at least a portion of the second shield 3828b when the sensor control device 3702 is assembled. The battery locator 3834, contact pocket 3836, module pocket 3838, and shield locator 3840 all extend a short distance within the inner surface of the mount 3708, such that the overall height H of the sensor control device 3702 may be reduced compared to conventional sensor control devices. The module pocket 3838 may also help minimize the diameter of the PCB 3804 by allowing PCB components to be disposed on both sides (i.e., the top and bottom).

[0069] 7A , the mount 3708 may further include a plurality of carrier grip features 3842 (two shown) defined around the circumference of the mount 3708. The carrier grip features 3842 are axially offset from a bottom 3844 of the mount 3708, where a transfer adhesive (not shown) can be applied during assembly. In contrast to conventional sensor control devices that generally include a conical carrier grip feature that intersects the bottom of the mount, the carrier grip features 3842 of the present disclosure are offset from the plane where the transfer adhesive is applied (i.e., the bottom 3844). This may prove advantageous to help ensure that the delivery system does not inadvertently adhere to the transfer adhesive during assembly. Furthermore, the carrier grip features 3842 of the present disclosure eliminate the need for a wavy transfer adhesive, which simplifies the manufacture of the transfer adhesive and eliminates the need to precisely register the transfer adhesive relative to the mount 3708. This also increases the bonding area and, therefore, the bond strength.

[0070] 7B , the bottom 3844 of the mount 3708 may include or otherwise define a plurality of grooves 3846, which may be defined at or near the periphery of the mount 3708 and spaced equidistant from one another. A transfer adhesive (not shown) may be coupled to the bottom 3844, and the grooves 3846 may be configured to help wick (migrate) moisture away from the sensor control unit 3702 toward the periphery of the mount 3708 during use. In some embodiments, the spacing of the grooves 3846 may sandwich a module pocket 3838 ( FIG. 7A ) defined on the opposite (inner) side of the mount 3708. As will be appreciated, alternating the positions of the grooves 3846 and the module pockets 3838 ensures that opposing features on either side of the mount 3708 do not extend into one another. This helps maximize material usage for the mount 3708 and may help maintain a minimum height H of the sensor control unit 3702. The module pocket 3838 may also significantly reduce mold sink and improve the flatness of the bottom 3844 where the transfer adhesive adheres.

[0071] 7B , the inner surface of the shell 3706 may also include or otherwise define a plurality of pockets or recesses configured to accommodate various components of the sensor control unit 3702 when the shell 3706 is mated to the mount 3708. For example, the inner surface of the shell 3706 may define an opposing battery locator 3848 that is positionable opposite the battery locator 3834 ( FIG. 7A ) of the mount 3708 when the sensor control unit 3702 is assembled and configured to accommodate a portion of the battery 3812. The opposing battery locator 3848 extends a short distance on the inner surface of the shell 3706, thereby helping to reduce the overall height H of the sensor control unit 3702.

[0072] A tip and sensor locator 3852 may also be provided or otherwise defined on the interior surface of the shell 3706. The tip and sensor locator 3852 may be configured to receive both a tip (not shown) and a portion of the sensor 3716. Furthermore, the tip and sensor locator 3852 may be configured to align and / or mate with a corresponding tip and sensor locator 2054 (FIG. 7A) provided on the interior surface of the mount 3708.

[0073] 8A-8C show an alternative sensor assembly / electronics assembly connection approach according to an embodiment of the present disclosure. As shown, the sensor assembly 14702 includes a sensor 14704, a connector support 14706, and a tip 14708. In particular, a recess or receptacle 14710 may be defined in the bottom of the mount of the electronics assembly 14712 to provide a location into which the sensor assembly 14702 may be received and coupled to the electronics assembly 14712, thereby fully assembling the sensor control device. The profile of the sensor assembly 14702 may be shaped in a manner that matches or is complementary to the receptacle 14710, which includes an elastomeric sealing member 14714 (coupled to the circuit board and including a conductive material aligned with the electrical contacts of the sensor 14704). 8C is formed when the sensor assembly 14702 is snap-fit ​​or otherwise adhered to the electronics assembly 14712 by driving the sensor assembly 14702 into the integrally formed recess 14710 of the electronics assembly 14712. This embodiment provides an integrated connector for the sensor assembly 14702 within the electronics assembly 14712.

[0074] Further information regarding sensor assemblies is provided in U.S. Publication Nos. 2013 / 0150691 and 2021 / 0204841, each of which is incorporated by reference in its entirety into this specification.

[0075] According to embodiments of the present disclosure, the sensor control device 102 can be modified to provide a one-piece architecture that can be subjected to sterilization techniques specifically designed for the one-piece architecture sensor control device. The one-piece architecture allows the sensor applicator 150 and sensor control device 102 to be shipped to a user in a single, sealed package that does not require any final user assembly steps. Rather, the user simply opens one package and then delivers the sensor control device 102 to the target monitoring location. The one-piece system architecture described herein can prove advantageous in eliminating component parts, various manufacturing process steps, and user assembly steps. As a result, packaging material and waste are reduced, and the possibility of user error or contamination of the system is mitigated.

[0076] Figures 9A and 9B are a side view and a side cross-sectional view, respectively, of an example embodiment of the sensor applicator 102 coupled with the applicator cap 210. More specifically, Figure 9A illustrates how the sensor applicator 102 is shipped and received by a user, and Figure 9B illustrates the sensor control unit 4402 disposed within the sensor applicator 102. Thus, the fully assembled sensor control unit 4402 may already be assembled and installed within the sensor applicator 102 before delivery to the user, thereby eliminating any additional assembly steps that the user would otherwise have to perform.

[0077] The fully assembled sensor control unit 4402 may be installed within the sensor applicator 102, and the applicator cap 210 may then be coupled to the sensor applicator 102. In some embodiments, the applicator cap 210 may be threaded onto the housing 208 and may include a tamper ring 4702. When the applicator cap 210 is rotated (e.g., unscrewed) relative to the housing 208, the tamper ring 4702 may shear, thereby releasing the applicator cap 210 from the sensor applicator 102.

[0078] According to the present disclosure, while installed within the sensor applicator 102, the sensor control unit 4402 may be subjected to gaseous chemical sterilization 4704 configured to sterilize the electronics housing 4404 and any other exposed portions of the sensor control unit 4402. To accomplish this, chemicals may be injected into a sterilization chamber 4706 cooperatively defined by the sensor applicator 102 and the interconnected cap 210. In some applications, chemicals may be injected into the sterilization chamber 4706 via one or more vents 4708 defined in the proximal end 610 of the applicator cap 210. Exemplary chemicals that may be used for gaseous chemical sterilization 4704 include, but are not limited to, ethylene oxide, vaporized hydrogen peroxide, nitrogen oxides (e.g., nitrous oxide, nitrogen dioxide, etc.), and steam.

[0079] The sensor 4410 and distal portion of tip 4412 are sealed within sensor cap 4416 so that chemicals used during the gas chemical sterilization process do not interact with the enzymes, chemicals, and biologicals provided in tail 4524 and other sensor components such as membrane coatings that regulate the influx of test substances.

[0080] Once the desired level of sterility assurance has been achieved within the sterilization chamber 4706, the gaseous solution may be removed and the sterilization chamber 4706 may be vented. Venting may be achieved by a series of vacuums followed by the circulation of a gas (e.g., nitrogen) or filtered air through the sterilization chamber 4706. Once the sterilization chamber 4706 is properly vented, the vent 4708 may be closed with a seal 4712 (shown in dotted lines).

[0081] In some embodiments, the seal 4712 may comprise two or more layers of different materials. A first layer may be made from a synthetic material (e.g., flash-spun high-density polyethylene fiber) such as Tyvek® available from DuPont®. Tyvek® is highly durable and puncture-resistant while allowing vapor transmission. A Tyvek® layer may be applied prior to the gas-chemical sterilization process, and following the gas-chemical sterilization process, a foil or other vapor- and moisture-resistant material layer may be sealed (e.g., heat-sealed) over the Tyvek® layer to prevent the ingress of contaminants and moisture into the sterilization chamber 4706. In other embodiments, the seal 4712 may comprise only a single protective layer applied to the applicator cap 210. In such embodiments, the single layer may be gas-permeable for the sterilization process but may also be able to protect from moisture and other harmful elements once the sterilization process is complete.

[0082] With the seal 4712 in place, the applicator cap 210 provides a barrier to outside contamination, thereby maintaining a sterile environment for the assembled sensor control device 4402 until the user removes (unscrews) the applicator cap 210. The applicator cap 210 may also prevent the adhesive patch 4714 from becoming contaminated and create a dust-free environment during shipping and storage.

[0083] 10A and 10B are isometric and side views, respectively, of another example of a sensor control device 5002 in accordance with one or more embodiments of the present disclosure. The sensor control device 5002 may be similar in some respects to the sensor control device 102 of FIG. 1 and therefore may be best understood by reference thereto. Furthermore, the sensor control device 5002 may replace the sensor control device 102 of FIG. 1 and, as a result, may be used with the sensor applicator 102 of FIG. 1, which may deliver the sensor control device 5002 to a target monitoring location on a user's skin.

[0084] 1 , however, the sensor control device 5002 may comprise a one-piece system architecture that does not require the user to open multiple packages and ultimately assemble the sensor control device 5002 prior to application. Rather, upon receipt by the user, the sensor control device 5002 may already be fully assembled and properly positioned within the sensor applicator 150 ( FIG. 1 ). To use the sensor control device 5002, the user only needs to open one barrier (e.g., applicator cap 708 of FIG. 3B ) before quickly delivering the sensor control device 5002 to the target monitoring location for use.

[0085] As shown, the sensor control unit 5002 includes an electronics housing 5004 that is generally disc-shaped and may have a circular cross-section. However, in other embodiments, the electronics housing 5004 may exhibit other cross-sectional shapes, such as oval or polygonal, without departing from the scope of the present disclosure. The electronics housing 5004 may be configured to house or otherwise contain various electrical components used to operate the sensor control unit 5002. In at least one embodiment, an adhesive patch (not shown) may be disposed on the bottom of the electronics housing 5004. The adhesive patch may be similar to adhesive patch 105 of FIG. 1 and, therefore, may help adhere the sensor control unit 5002 to a user's skin for use.

[0086] As shown, the sensor control device 5002 includes an electronics housing 5004 that includes a shell 5006 and a mount 5008 that can mate with the shell 5006. The shell 5006 can be secured to the mount 5008 via a variety of methods, such as a snap-fit ​​engagement, an interference fit, sonic welding, one or more mechanical fasteners (e.g., screws), a gasket, an adhesive, or any combination thereof. In some cases, the shell 5006 can be secured to the mount 5008 so that a sealed interface is created therebetween.

[0087] The sensor control device 5002 may further include a sensor 5010 (partially visible) and a tip 5012 (partially visible) that are used to facilitate transcutaneous delivery of the sensor 5010 under the user's skin during application of the sensor control device 5002. As shown, corresponding portions of the sensor 5010 and tip 5012 extend distally from the bottom of the electronics housing 5004 (e.g., mount 5008). The tip 5012 may include a tip hub 5014 that is configured to secure and deliver the tip 5012. As best seen in FIG. 10B , the tip hub 5014 may include or otherwise define a mating member 5016. To couple the tip 5012 to the sensor control device 5002, the tip 5012 may be advanced axially through the electronics housing 5004 until the tip hub 5014 engages the top surface of the shell 5006 and the mating member 5016 extends distally from the bottom of the mount 5008. Once the tip 5012 penetrates the electronics housing 5004, an exposed portion of the sensor 5010 may be received within a hollow or recessed portion (arch) of the tip 5012. The remainder of the sensor 5010 is disposed within the interior of the electronics housing 5004.

[0088] The sensor control unit 5002 may further include a sensor cap 5018, which is shown exploded or separated from the electronics housing 5004 in FIGS. 10A-10B . The sensor cap 5018 may be removably coupled to the sensor control unit 5002 (e.g., the electronics housing 5004) at or near the bottom of the mount 5008. The sensor cap 5018 may serve to provide a sealed barrier surrounding the exposed portions of the sensor 5010 and tip 5012, protecting them from gaseous chemical sterilization. As shown, the sensor cap 5018 may comprise a generally cylindrical body having a first end 5020 a and a second end 5020 b opposite the first end 5020 a. The first end 5020 a may be open to provide access to an interior chamber 5022 defined within the body. In contrast, the second end 5020 b may be closed and may include or otherwise define an engagement feature 5024. As described herein, the engagement feature 5024 may help to fit the sensor cap 5018 to a cap (e.g., applicator cap 708 of FIG. 3B) of a sensor applicator (e.g., sensor applicator 150 of FIGS. 1 and 3A-3G) and may help to remove the sensor cap 5018 from the sensor control device 5002 when the cap is removed from the sensor applicator.

[0089] The sensor cap 5018 may be removably coupled to the electronics housing 5004 at or near the bottom of the mount 5008. More specifically, the sensor cap 5018 may be removably coupled to a mating member 5016 extending distally from the bottom of the mount 5008. In at least one embodiment, for example, the mating member 5016 may define a set of external threads 5026a (FIG. 10B) that are matable with a set of internal threads 5026b (FIG. 10A) defined by the sensor cap 5018. In some embodiments, the external and internal threads 5026a,b may comprise a flat thread design (e.g., lack of a helical curve), which may prove advantageous in molding the part. Alternatively, the external and internal threads 5026a,b may comprise a helical thread engagement. Thus, the sensor cap 5018 may be threadedly coupled to the sensor control device 5002 at the mating member 5016 of the tip hub 5014. In other embodiments, the sensor cap 5018 may be removably coupled to the mating member 5016 via other types of engagement, including, but not limited to, an interference fit or a friction fit, or a frangible member or material that can be broken with minimal separation force (e.g., axial or rotational force).

[0090] In some embodiments, the sensor cap 5018 may comprise a monolithic (single) structure extending between the first and second ends 5020 a, b. However, in other embodiments, the sensor cap 5018 may comprise two or more components. In the illustrated embodiment, for example, the sensor cap 5018 may include a sealing ring 5028 disposed at the first end 5020 a and a desiccant cap 5030 disposed at the second end 5020 b. The sealing ring 5028 may be configured to help seal the internal chamber 5022, as described in more detail below. In at least one embodiment, the sealing ring 5028 may comprise an elastomeric O-ring. The desiccant cap 5030 may contain or comprise a desiccant that helps maintain a preferred humidity level within the internal chamber 5022. The desiccant cap 5030 may also define or otherwise comprise the engagement feature 5024 of the sensor cap 5018.

[0091] 11A-11C are step-by-step cross-sectional side views illustrating the assembly of the sensor applicator 102 with a sensor control device 5002, according to one or more embodiments. Once the sensor control device 5002 is fully assembled, it may be installed within the sensor applicator 102. Referring to FIG. 11A, the tip hub 5014 may include or otherwise define a hub snap pole 5302 configured to help couple the sensor control device 5002 to the sensor applicator 102. More specifically, the sensor control device 5002 may be advanced into the sensor applicator 102, and the hub snap pole 5302 may be received by a corresponding arm 5304 of a tip carrier 5306 disposed within the sensor applicator 102.

[0092] 11B, the sensor control device 5002 is shown received by the tip carrier 5306 and thus secured within the sensor applicator 102. Once the sensor control device 5002 is installed within the sensor applicator 102, the applicator cap 210 may be coupled to the sensor applicator 102. In some embodiments, the applicator cap 210 and the housing 208 may have opposing, interlocking threads 5308 that allow the applicator cap 210 to be threaded onto the housing 208 in a clockwise (or counterclockwise) direction, thereby securing the applicator cap 210 to the sensor applicator 102.

[0093] As shown, the sheath 212 is also positioned within the sensor applicator 102, which may include a sheath locking mechanism 5310 configured to ensure that the sheath 212 does not prematurely collapse during an impact event. In the embodiment shown, the sheath locking mechanism 5310 may comprise a threaded engagement between the applicator cap 210 and the sheath 212. More specifically, one or more internal threads 5312a may be defined or otherwise provided on an interior surface of the applicator cap 210, and one or more external threads 5312b may be defined or otherwise provided on the sheath 212. The internal or external threads 5312a,b may be configured to threadably engage and allow the applicator cap 210 to threadably engage with the sensor applicator 102 at the threads 5308. The female and male threads 5312 a,b may have the same thread pitch as the threads 5308 that allow the applicator cap 210 to be threaded onto the housing 208 .

[0094] 11C , applicator cap 210 is shown as being fully threaded (coupled) to housing 208. As shown, applicator cap 210 further includes, or may otherwise define, a cap post 5314 centrally located within and extending proximally from the bottom of applicator cap 210. Cap post 5314 may be configured to receive at least a portion of sensor cap 5018 as applicator cap 210 threads onto housing 208.

[0095] Once the sensor control unit 5002 is installed in the sensor applicator 102 and the applicator cap 210 is properly secured, the sensor control unit 5002 can undergo a gas chemical sterilization process configured to sterilize the electronics housing 5004 and any other exposed portions of the sensor control unit 5002. Because the sensor 5010 and the distal portion of the tip 5012 are sealed within the sensor cap 5018, the chemicals used during the gas chemical sterilization process cannot interact with other sensor components, such as the enzymes, chemicals, and biologicals provided on the tail 5104 and the membrane coating that regulates the influx of the analyte.

[0096] 12A-12C are step-by-step cross-sectional side views illustrating assembly and disassembly of an alternative embodiment of a sensor applicator 102 with a sensor control device 5002, according to one or more further embodiments. As generally described above, the fully assembled sensor control device 5002 may be attached to the sensor applicator 102 by coupling the hub snap pole 5302 into the arm 5304 of the tip carrier 5306 disposed within the sensor applicator 102.

[0097] In the illustrated embodiment, the sheath arm 5604 of the sheath 212 may be configured to interact with a first detent 5702a and a second detent 5702b defined within the housing 208. The first detent 5702a may alternatively be referred to as a "locking" detent, and the second detent 5702b may alternatively be referred to as a "firing" detent. When the sensor control device 5002 is initially attached to the sensor applicator 102, the sheath arm 5604 may be received within the first detent 5702a. As discussed below, the sheath 212 may be actuated to move the sheath arm 5604 to the second detent 5702b, thereby placing the sensor applicator 102 in the fired position.

[0098] 12B , applicator cap 210 is aligned with and advanced toward housing 208, such that sheath 212 is received within applicator cap 210. Instead of rotating applicator cap 210 relative to housing 208, threads on applicator cap 210 may snap onto corresponding threads on housing 208 to couple applicator cap 210 to housing 208. Axial cuts or slots 5703 (one shown) defined in applicator cap 210 may allow a portion of applicator cap 210 near its threads to flex outward and snap into engagement with threads on housing 208. Once applicator cap 210 is snapped onto housing 208, sensor cap 5018 may correspondingly snap onto cap post 5314.

[0099] 11A-11C , the sensor applicator 102 may include a sheath fixation mechanism configured to ensure that the sheath 212 does not prematurely collapse during an impact event. In the illustrated embodiment, the sheath fixation mechanism includes one or more ribs 5704 (one shown) defined near a base of the sheath 212 and configured to interact with one or more ribs 5706 (two shown) and a shoulder 5708 defined near a base of the applicator cap 210. The rib 5704 may be configured to interlock between the rib 5706 and the shoulder 5708 during attachment of the applicator cap 210 to the housing 208. More specifically, once applicator cap 210 is snapped onto housing 208, applicator cap 210 may be rotated (e.g., clockwise), which positions rib 5704 of sheath 212 between rib 5706 and shoulder 5708 of applicator cap 210, thereby "locking" applicator cap 210 in place until a user counter-rotates applicator cap 210 and removes applicator cap 210 for use. The engagement of rib 5704 with rib 5706 and shoulder 5708 of applicator cap 210 may also prevent sheath 212 from prematurely collapsing.

[0100] 12C, the applicator cap 210 is removed from the housing 208. Similar to the embodiment of FIGS. 21A-21C, the applicator cap 210 may be removed by counter-rotating the applicator cap 210, which correspondingly rotates the cap post 5314 in the same direction, unscrewing the sensor cap 5018 from the fitting 5016, generally as described above. Additionally, removing the sensor cap 5018 from the sensor control device 5002 exposes the sensor 5010 and a distal portion of the tip 5012.

[0101] When applicator cap 210 is unthreaded from housing 208, rib 5704 defined on sheath 212 may slidingly engage an upper portion of rib 5706 defined on applicator cap 210. The upper portion of rib 5706 may provide a corresponding ramp that, when applicator cap 210 is rotated, causes upward movement of sheath 212, which deflects sheath arm 5604 out of engagement with first detent 5702a so as to be received in second detent 5702b. As the sheath 212 moves to the second detent 5702b, the radial shoulder 5614 moves out of radial engagement with the carrier arms 5608, allowing the passive spring force of the spring 5612 to urge the tip carrier 5306 upward, disengaging the carrier arms 5608 from engagement with the grooves 5610. As the tip carrier 5306 moves upward within the housing 208, the engaging member 5016 may correspondingly retract until it is flush, substantially flush, or near-flush with the bottom of the sensor control device 5002. At this point, the sensor applicator 102 is in the fired position. Thus, in this embodiment, removing the applicator cap 210 correspondingly retracts the engaging member 5016.

[0102] 13A-13F show detailed example embodiments of the internal device mechanisms that "fire" the applicator 216 to apply the sensor control unit 222 to a user and safely retract the tip 1030 into the used applicator 216. Together, these figures represent an example sequence for driving the tip 1030 (carrying a sensor coupled to the sensor control unit 222) into a user's skin, retracting the tip leaving the sensor in operable contact with the user's interstitial fluid, and adhesively adhering the sensor control unit to the user's skin. Modifications of such operations for use with alternative applicator assembly embodiments and components can be understood by those skilled in the art with reference thereto. Additionally, the applicator 216 can be a sensor applicator having a one-piece or two-piece architecture as disclosed herein.

[0103] 13A , the sensor 1102 is supported within the tip 1030, immediately above the user's skin 1104. Rails 1106 (optionally, three of them) of the upper guide section 1108 may be provided to control movement of the applicator 216 relative to the sheath 318. The sheath 318 is retained by detent features 1110 within the applicator 216, and an appropriate downward force along the longitudinal axis of the applicator 216 may overcome the resistance provided by the detent features 1110 to translate the tip 1030 and sensor control unit 222 along the longitudinal axis into (and onto) the user's skin 1104. Additionally, a catch arm 1112 of the sensor carrier 1022 engages the tip retraction assembly 1024 to maintain the tip 1030 in position relative to the sensor control unit 222.

[0104] 13B, a user force is applied over or above the detent feature 1110, causing the sheath 318 to collapse within the housing 314, translating the sensor control unit 222 (along with accompanying components) downward along the longitudinal axis as shown by arrow L. The inner diameter of the upper guide section 1108 of the sheath 318 constrains the position of the carrier arm 1112 through the entire stroke of the sensor / tip insertion process. The retention of the stop surface 1114 of the carrier arm 1112 against the complementary surface 1116 of the tip retraction assembly 1024, along with the fully biased return spring 1118, maintains the member's position. According to an embodiment, rather than employing user force to translate the sensor control unit 222 downward along the longitudinal axis as shown by arrow L, the housing 314 may include a button (e.g., but not limited to, a push button) that activates a drive spring (e.g., but not limited to, a coil spring) to actuate the sensor control unit 222.

[0105] In Figure 13C, the sensor 1102 and tip 1030 have reached their fully inserted depth, causing the carrier arm 1112 to clear the inner diameter of the upper guide section 1108. The compressive force of the coil return spring 1118 then drives the angled stop surface 1114 radially outward, releasing the force and driving the tip carrier 1102 of the tip retraction assembly 1024, pulling the (slotted or otherwise configured) tip 1030 outward from the user and away from the sensor 1102, as shown by arrow R in Figure 13D.

[0106] With tip 1030 fully retracted, as shown in Figure 13E, upper guide section 1108 of sheath 318 is secured by final securement feature 1120. As shown in Figure 13F, the used applicator assembly 216 is removed from the insertion site, leaving behind sensor control device 222, with tip 1030 safely secured inside applicator assembly 216. The used applicator assembly 216 is now ready for disposal.

[0107] Operation of the applicator 216 when applying the sensor control device 222 is designed to provide the user with the sensation that both insertion and retraction of the tip 1030 are performed automatically by the applicator's 216 internal mechanisms. In other words, the present invention avoids the user experiencing the sensation of manually driving the tip 1030 into the user's skin. That is, once the user applies sufficient force to overcome the resistance of the applicator's 216 detent features, the resulting movement of the applicator 216 is perceived as an automatic response to a "triggered" applicator. Even though all of the driving force is provided by the user and no additional biasing / driving means are used to insert the tip 1030, the user does not perceive that they are supplying additional force to drive the tip 1030 and pierce the skin. As described above in FIG. 13C , retraction of the tip 1030 is automated by the applicator's 216 coil return spring 1118.

[0108] With respect to any of the applicator embodiments described herein and any of its components, including, but not limited to, embodiments of the tip, tip module, and sensor module, those skilled in the art will understand that the embodiments can be sized and configured for use with a sensor configured to detect analyte levels in bodily fluids within the epidermis, dermis, or subcutaneous tissue of a subject. In some embodiments, for example, the tip and distal portion of an analyte sensor disclosed herein can both be sized and configured to be positioned at a particular distal depth (i.e., the furthest point of penetration within a tissue or layer of a subject's body, e.g., the epidermis, dermis, or subcutaneous tissue). With respect to some applicator embodiments, those skilled in the art will understand that particular embodiments of the tip can be sized and configured to be positioned at a different distal depth within a subject's body relative to the final distal depth of the analyte sensor. In some embodiments, for example, the tip can be positioned at a first distal depth within the subject's epidermis, while the distal portion of the analyte sensor can be positioned at a second distal depth within the subject's dermis prior to retraction. In other embodiments, the tip may be positioned at a first distal depth within the subject's dermis prior to retraction, while the distal portion of the analyte sensor may be positioned at a second distal depth within the subject's subcutaneous tissue. In yet other embodiments, the tip may be positioned at a first distal depth and the analyte sensor at a second distal depth prior to retraction, where both the first distal depth and the second distal depth are within the same layer or tissue of the subject's body.

[0109] Additionally, with respect to any of the applicator embodiments described herein, one skilled in the art will understand that the analyte sensor and one or more structural components coupled to the analyte sensor, including, but not limited to, one or more spring mechanisms, may be positioned within the applicator in an eccentric position relative to one or more axes of the applicator. In some applicator embodiments, for example, the analyte sensor and spring mechanism may be positioned in a first eccentric position relative to the applicator axis on a first side of the applicator, and the sensor electronics may be positioned in a second eccentric position relative to the applicator axis on a second side of the applicator. In other applicator embodiments, the analyte sensor, spring mechanism, and sensor electronics may be positioned in an eccentric position relative to the applicator axis on the same side. One skilled in the art will understand that other permutations and configurations in which any or all of the analyte sensor, spring mechanism, sensor electronics, and other applicator components are positioned in central or eccentric positions relative to one or more axes of the applicator are possible and fully within the scope of the present disclosure.

[0110] Further details of suitable devices, systems, methods, components, and their operation, along with relevant features, are described in Rao et al., International Publication No. WO 2018 / 136898, Thomas et al., International Publication No. WO 2019 / 236850, Thomas et al., International Publication No. WO 2019 / 236859, Thomas et al., International Publication No. WO 2019 / 236876, and U.S. Patent Publication No. 2020 / 0196919, filed June 6, 2019, each of which is incorporated herein by reference in its entirety. Further details regarding embodiments of applicators, their components, and variations thereof are described in U.S. Patent Publication Nos. 2013 / 0150691, 2016 / 0331283, and 2018 / 0235520, all of which are incorporated herein by reference in their entirety for all purposes. Further details regarding embodiments of the tip module, tip, their components, and variations thereof are described in U.S. Patent Publication No. 2014 / 0171771, which is incorporated herein by reference in its entirety for all purposes.

[0111] Biochemical sensors can be described by one or more sensing properties. A common sensing property is referred to as the sensitivity of a biochemical sensor, which is a measure of the sensor's responsiveness to the concentration of the chemical or composition it is designed to detect. In electrochemical sensors, this response can be in the form of current (amperometric) or charge (coulometric). In other types of sensors, the response can be in a different form, such as photon intensity (e.g., optical light). The sensitivity of a biochemical analyte sensor can vary depending on several factors, including whether the sensor is in vitro or in vivo.

[0112] FIG. 14 is a graph showing the in vitro sensitivity of an amperometric analyte sensor. In vitro sensitivity can be obtained by testing the sensor in vitro at various analyte concentrations and then performing regression (e.g., linear or nonlinear) or other curve fitting on the resulting data. In this example, the sensitivity of the analyte sensor is linear or substantially linear and may be modeled according to the equation y = mx + b, where y is the electrical output current of the sensor, x is the analyte level (or concentration), m is the slope of the sensitivity, and b is the intercept of the sensitivity, with the intercept generally corresponding to background signal (e.g., noise). For sensors with linear or substantially linear responses, the analyte level corresponding to a given current can be determined from the slope and intercept of the sensitivity. Sensors with nonlinear sensitivity require additional information to determine the analyte level resulting from the sensor's output current, and those skilled in the art are familiar with methods for modeling nonlinear sensitivity. In certain embodiments of an in vivo sensor, the in vitro sensitivity may be the same as the in vivo sensitivity, while in other embodiments, a transfer (or transformation) function is used to convert the in vitro sensitivity to an in vivo sensitivity applicable to the sensor's intended in vivo use.

[0113] Calibration is a technique for improving or maintaining accuracy by adjusting the measured output of a sensor to reduce the difference from the sensor's expected output. One or more parameters describing the sensing characteristics of the sensor, such as its sensitivity, are established for use in calibration adjustments.

[0114] Certain in vivo analyte monitoring systems require calibration after the sensor is implanted in a user or patient, either through user intervention or by the system itself in an automated manner. For example, when user intervention is required, the user performs an in vitro measurement (e.g., a blood glucose (BG) measurement using a fingerstick and an in vitro test strip) while the analyte sensor is implanted and inputs it into the system. The system then compares the in vitro measurement with the in vivo signal and uses the difference to determine an estimate of the sensor's in vivo sensitivity. The in vivo sensitivity may then be used in an algorithmic process to convert data collected by the sensor into a value indicative of the user's analyte level. This and other processes requiring user action to perform calibration are referred to as "user calibration." Systems may require user calibration due to instability in sensor sensitivity, such as sensitivity drifting or changing over time. Thus, multiple user calibrations (e.g., on a periodic (e.g., daily) schedule, a variable schedule, or as needed) may be required to maintain accuracy. Although the embodiments described herein may incorporate some degree of user calibration for particular implementations, this is generally not preferred as it requires the user to perform painful or otherwise cumbersome BG measurements and can introduce user error.

[0115] Some in vivo analyte monitoring systems can periodically adjust calibration parameters by using automated measurements of sensor characteristics made by the system itself (e.g., processing circuitry running software). Repeated adjustment of sensor sensitivity based on variables measured by the system (not the user) is commonly referred to as "system" (or automatic) calibration and can be performed with or without user calibration, such as an early BG measurement. As with repeated user calibration, repeated system calibration is typically necessitated by drift in sensor sensitivity over time. Thus, while the embodiments described herein can be used with some degree of automatic system calibration, preferably the sensor sensitivity is relatively stable over time so that post-implant calibration is not required.

[0116] Some in vivo analyte monitoring systems operate with factory-calibrated sensors. Factory calibration refers to the determination or estimation of one or more calibration parameters before distribution to users or healthcare professionals (HCPs). The calibration parameters may be determined by the sensor manufacturer (or the manufacturer of other components of the sensor control device, if the two entities are different). Many in vivo sensor manufacturing processes produce sensors in groups or batches called production lots, production-stage lots, or simply lots. A single lot may contain thousands of sensors.

[0117] The sensor may include calibration codes or parameters that are derived or determined during one or more sensor manufacturing processes, coded or programmed into the data processing device of the analyte monitoring system as part of the manufacturing process, or carried on the sensor itself, for example, as a bar code, laser tag, RFID tag, or other machine-readable information carried on the sensor. If the code is provided to a receiver (or other data processing device), user calibration during in vivo use of the sensor may be unnecessary, or the frequency of in vivo calibration during sensor wear may be reduced. In embodiments in which the calibration code or parameters are provided on the sensor itself, the calibration code or parameters may be automatically transmitted or provided to the data processing device in the analyte monitoring system prior to or upon initiation of sensor use.

[0118] Some in vivo analyte monitoring systems operate with sensors that may be one or more of factory-calibrated, system-calibrated, and / or user-calibrated. For example, a sensor may be equipped with a calibration code or parameters that may enable factory calibration. If information is provided to the receiver (e.g., entered by a user), the sensor may operate as a factory-calibrated sensor. If information is not provided to the receiver, the sensor may operate as a user-calibrated sensor and / or a system-calibrated sensor.

[0119] In further aspects, programming or executable instructions may be provided or stored in the data processing device and / or receiver / controller unit of the analyte monitoring system to provide time-varying adjustment algorithms for the in-vivo sensor during use. For example, based on retrospective statistical analysis of analyte sensors used in vivo and corresponding glucose level feedback, a time-based predetermined or analytical curve or database may be generated and configured to provide further adjustments to one or more in-vivo sensor parameters or other factors to compensate for potential sensor drift in the stability profile.

[0120] In accordance with the disclosed subject matter, an analyte monitoring system can be configured to compensate or adjust sensor sensitivity based on a sensor drift profile. A time-varying parameter β(t) may be defined or determined based on an analysis of sensor behavior during in vivo use, and a time-varying drift profile may be determined. In certain aspects, the compensation or adjustment to sensor sensitivity may be programmed in a receiver unit, controller, or data processor of the analyte monitoring system, such that the compensation or adjustment, or both, may be performed automatically and / or iteratively as sensor data is received from the analyte sensor. In accordance with the disclosed subject matter, the adjustment or compensation algorithm may be user-initiated or executed (rather than self-initiated or executed) such that the adjustment or compensation to the analyte sensor sensitivity profile is performed or executed upon user initiation or activation of a corresponding function or routine or when the user enters a sensor calibration code.

[0121] According to the disclosed subject matter, each sensor in a sensor lot (in some examples, not including sample sensors used for in vitro testing) can be non-destructively inspected to determine or measure its characteristics, such as film thickness at one or more points on the sensor, and other characteristics, including physical characteristics such as surface area / volume of the active area, can be measured or determined. Such measurements or determinations may be performed in an automated manner, for example, using an optical scanner or other suitable measurement device or system, and the determined sensor characteristics of each sensor in the sensor lot are compared to corresponding average values ​​based on sample sensors for possible correction of calibration parameters or codes assigned to each sensor. For example, for a calibration parameter defined as sensor sensitivity, sensitivity is approximately inversely proportional to film thickness; thus, for example, for a sensor having a measured film thickness that is about 4% greater than the average film thickness of sensors sampled from the same sensor lot as the sensor, in one embodiment the sensitivity assigned to that sensor is the average sensitivity determined from the sampled sensors divided by 1.04. Similarly, sensitivity is approximately proportional to the active area of ​​a sensor, so for a sensor with a measured active area that is approximately 3% smaller than the average active area of ​​sensors sampled from the same sensor lot, the sensitivity assigned to that sensor is the average sensitivity multiplied by 0.97. The assigned sensitivity may be determined from the average sensitivity from the sampled sensors by multiple successive adjustments for each test or measurement of the sensor. In certain embodiments, the test or measurement of each sensor may further include measurement of the film uniformity or structure in addition to the film thickness and / or surface area or volume of the active sensing area.

[0122] Further information regarding sensor calibration is provided in U.S. Publication No. 2010 / 00230285 and U.S. Publication No. 2019 / 0274598, each of which is incorporated by reference herein in its entirety.

[0123] The storage memory 5030 of the sensor 110 may include software blocks related to the communication protocol of the communication module. For example, the storage memory 5030 may include a BLE service software block whose functions provide an interface that makes the BLE module 5041 available to the computing hardware of the sensor 110. These software functions may include a BLE logical interface and an interface parser. BLE services provided by the communication module 5040 may include a generic access profile service, a generic attribute service, a generic access service, a device information service, a data transmission service, and a security service. The data transmission service may be a primary service used to transmit data such as sensor control data, sensor status data, analyte measurement data (past and present), and event log data. Sensor status data may include error data, current active time, and software state. Analyte measurement data may include information such as current and past raw measurements, current and past values ​​after processing using appropriate algorithms or models, predictions and trends of measurement levels, comparisons of other values ​​to patient-specific averages, calls to action determined by algorithms or models, and other similar types of data.

[0124] In accordance with aspects of the disclosed subject matter, as embodied herein, sensor 110 may be configured to communicate with multiple devices simultaneously by adapting the characteristics of the communication protocol or medium supported by the hardware and radio of sensor 110. As an example, BLE module 5041 of communication module 5040 may comprise software or firmware to enable multiple simultaneous connections between sensor 110 as a central device and other devices as peripheral devices, or sensor 110 as a peripheral device when another device is the central device.

[0125] A connection and subsequent communication session between two devices using a communication protocol such as BLE may be characterized by a similar physical channel operating between the two devices (e.g., the sensor 110 and the data receiving device 120). The physical channel may include a single channel or a set of channels, including, for example, but not limited to, using a common clock and channel or an agreed-upon set of channels determined by a frequency hopping sequence. The communication sessions may use a similar amount of available communication spectrum, and multiple such communication sessions may exist in close proximity. In certain embodiments, each set of devices in a communication session uses a different physical channel or set of channels to manage interference with similarly nearby devices.

[0126] For purposes of illustration and not limitation, reference will be made to an exemplary embodiment of a process for sensor-receiver connection for use with the disclosed subject matter. First, the sensor 110 repeatedly advertises its connection information to its surroundings in search of the data receiving device 120. The sensor 110 can periodically repeat the advertisement until a connection is established. The data receiving device 120 detects the advertising packet and scans and filters for the sensor 120 to connect via the data provided in the advertising packet. Next, the data receiving device 120 sends a scan request command, and the sensor 110 responds with a scan response packet providing additional details. Next, the data receiving device 120 sends a connection request using the Bluetooth® device address associated with the data receiving device 120. The data receiving device 120 may also continuously request to establish a connection to the sensor 110 with a specific Bluetooth® device address. The device then establishes the initial connection so that data exchange can begin. The device begins the process of initializing the data exchange service and performing a mutual authentication process.

[0127] During the first connection between the sensor 110 and the data receiving device 120, the data receiving device 120 may initialize a service, feature, and attribute discovery process. The data receiving device 120 may evaluate these characteristics of the sensor 110 and store them for use during the next connection. The device then enables notification of customized security services to be used for mutual authentication of the sensor 110 and the data receiving device 120. The mutual authentication process can be automated and does not require user intervention. After successful completion of the mutual authentication process, the sensor 110 sends a connection parameter update requesting the data receiving device 120 to use connection parameter settings that are preferred for the sensor 110 and configured to maximize longevity.

[0128] The data receiving device 120 then executes a sensor control process to backfill historical data, current data, event logs, and factory data. As an example, for each type of data, the data receiving device 120 sends a request to initiate the backfill process. The request may specify a range of records, defined, for example, based on measurements, timestamps, etc., as needed. The sensor 110 responds with the requested data until all previously untransmitted data in the sensor 110's memory is delivered to the data receiving device 120. The sensor 110 may respond to a backfill request from the data receiving device 120 that all data has already been transmitted. Once backfilling is complete, the data receiving device 120 may notify the sensor 110 that it is ready to receive periodic measurements. The sensor 110 may transmit measurements over multiple notifications on a repeating basis. As embodied herein, the multiple notifications may be redundant notifications to ensure that the data is transmitted correctly. Alternatively, the multiple notifications may comprise a single payload.

[0129] For purposes of illustration and not limitation, reference will be made to an exemplary embodiment of a process for sending a shutdown command to the sensor 110. The shutdown operation is performed, for example, when the sensor 110 is in an error state, an insertion failure state, or a sensor expired state. If the sensor 110 is not in one of these states, the sensor 110 may record the command and execute the shutdown when the sensor 110 transitions to the error state or the sensor expired state. The data sink 120 sends an appropriately formatted shutdown command to the sensor 110. If the sensor 110 is actively processing another command, the sensor 110 responds with a standard error response indicating that the sensor 110 is busy. Otherwise, the sensor 110 sends a response upon receiving the command. Additionally, to acknowledge that the sensor 110 received the command, the sensor 110 sends a success notification via the sensor control property. The sensor 110 registers the shutdown command. At the next appropriate opportunity (e.g., depending on the current sensor state, as described herein), the sensor 110 shuts down.

[0130] For purposes of illustration and not limitation, reference is made to an exemplary embodiment of a high-level depiction of a state machine representation 6000 of actions that may be performed by the sensor 110 shown in FIG. 15 . After initialization, the sensor enters a state 6005 associated with manufacturing the sensor 110. In the manufacturing state 6005, the sensor 110 may be configured for operation, e.g., the storage memory 5030 may be written. At various times while in state 6005, the sensor 110 checks for a received command to proceed to the save state 6015. Upon entering the save state 6015, the sensor performs a software integrity check. While in the save state 6015, the sensor may also receive an actuation request command before proceeding to the insertion detect state 6025.

[0131] Upon entering state 6025, the sensor 110 may store information about authorized devices to communicate with the configured sensor during operation or initialize algorithms related to performing and interpreting measurements from the sensing hardware 5060. The sensor 110 may also initialize a lifecycle timer responsible for maintaining an active count of the sensor's 110 operation time and begin communicating with authorized devices to transmit recorded data. While in insertion detection state 6025, the sensor may enter state 6030, in which the sensor 110 checks whether the operation time equals a predetermined threshold. This operation time threshold may correspond to a timeout function for determining whether the insertion is successful. If the operation time threshold is reached, the sensor 110 proceeds to state 6035, in which the sensor 110 checks whether the average data read volume is greater than a threshold corresponding to the expected data read volume to trigger the detection of a successful insertion. If the data read volume is lower than the threshold while in state 6035, the sensor proceeds to state 6040, corresponding to an insertion failure. If the data read volume meets the threshold, the sensor proceeds to active pair state 6055.

[0132] The active pair state 6055 of the sensor 110 indicates the state during which the sensor 110 is operating normally by recording measurements, processing the measurements, and reporting them as necessary. While in the active pair state 6055, the sensor 110 transmits measurements or attempts to establish a connection with the receiving device 120. The sensor 110 also increases its operating time. When the sensor 110 reaches a predetermined operating time threshold (e.g., when the operating time reaches a predetermined threshold), the sensor 110 transitions to the active expired state 6065. The active expired state 6065 of the sensor 110 indicates the state during which the sensor 110 has been operating for its maximum predetermined time.

[0133] While in the active expired state 6065, the sensor 110 may perform operations generally related to terminating operation and ensuring that collected measurements are securely transmitted to receiving devices as needed. For example, while in the active expired state 6065, the sensor 110 may transmit collected data and, if a connection is not feasible, may increase attempts to discover and establish a connection with a nearby authenticated device. While in the active expired state 6065, the sensor 110 may receive a shutdown command in state 6070. If a shutdown command is not received, the sensor 110 may also check in state 6075 whether the operation time has exceeded a terminal operation threshold. The terminal operation threshold may be based on the battery life of the sensor 110. The normal termination state 6080 corresponds to the final operation of the sensor 110 and ultimately shuts down the sensor 110.

[0134] Before the sensor is activated, the ASIC 5000 is in a low-power storage mode. For example, the activation process may begin when an incident RF field (e.g., an NFC field) drives the voltage of the power supply to the ASIC 5000 above a reset threshold, causing the sensor 110 to proceed to a wake-up state. While in the wake-up state, the ASIC 5000 enters an activation sequence state. The ASIC 5000 then activates the communication module 5040. The communication module 5040 is initialized and triggers a power-on self-test. The power-on self-test may include the ASIC 5000 communicating with the communication module 5040 using a predetermined sequence of reading and writing data to verify that the memory and one-time programmable memory are not corrupted.

[0135] When the ASIC 5000 first enters measurement mode, an insertion detection sequence is executed to verify that the sensor 110 is properly placed on the patient's body before proper measurements can be taken. First, the sensor 110 interprets commands to activate the measurement configuration process, causing the ASIC 5000 to enter measurement command mode. Next, the sensor 110 temporarily enters a measurement lifecycle state, performing several consecutive measurements to check for successful insertion. The communications module 5040 or the ASIC 5000 evaluates the measurement results to determine successful insertion. If insertion is deemed successful, the sensor 110 enters a measurement state, where the sensor 110 begins taking periodic measurements using the sensing hardware 5060. If the sensor 110 determines that insertion was not successful, the sensor 110 is triggered into insertion failure mode, and the ASIC 5000 is instructed to return to storage mode, while the communications module 5040 disables itself.

[0136] 1A further illustrates an example operating environment for providing over-the-air ("OTA") updates for use with the techniques described herein. An operator of the analyte monitoring system 100 may bundle updates for the data receiving device 120 or sensor 110 into updates for an application running on the multipurpose data receiving device 130. Using available communication channels between the data receiving device 120, the multipurpose data receiving device 130, and the sensor 110, the multipurpose data receiving device 130 may receive periodic updates for the data receiving device 120 or sensor 110 and initiate installation of the updates on the data receiving device 120 or sensor 110. Applications that enable the multipurpose data receiving device 130 to communicate with the analyte sensor 110, the data receiving device 120, and / or a remote application server 150 can update software or firmware on the data receiving device 120 or sensor 110 without wide area network capability, so that the multipurpose data receiving device 130 serves as an installation or update platform for the data receiving device 120 or sensor 110.

[0137] As embodied herein, a remote application server 150 operated by the manufacturer of the analyte sensor 110 and / or the operator of the analyte monitoring system 100 may provide software and firmware updates to the devices of the analyte monitoring system 100. In particular embodiments, the remote application server 150 may provide updated software and firmware to the user device 140 or directly to the multipurpose data receiving device. As embodied herein, the remote application server 150 may also provide application software updates to the application storefront server 160 using an interface provided by the application storefront. The multipurpose data receiving device 130 may periodically contact the application storefront server 160 to download and install updates.

[0138] After the multipurpose data receiving device 130 downloads an application update including a firmware or software update for the data receiving device 120 or the sensor 110, the data receiving device 120 or the sensor 110 and the multipurpose data receiving device 130 establish a connection. The multipurpose data receiving device 130 determines that a firmware or software update is available for the data receiving device 120 or the sensor 110. The multipurpose data receiving device 130 may prepare the software or firmware update for delivery to the data receiving device 120 or the sensor 110. As an example, the multipurpose data receiving device 130 may compress or split data associated with the software or firmware update, encrypt or decrypt the firmware or software update, or perform an integrity check on the firmware or software update. The multipurpose data receiving device 130 transmits data for the firmware or software update to the data receiving device 120 or the sensor 110. The multipurpose data receiving device 130 may also transmit a command to the data receiving device 120 or the sensor 110 to initiate the update. Additionally or alternatively, the multipurpose data receiving device 130 may provide a notification to a user of the multipurpose data receiving device 130 and may include instructions to facilitate the update, such as instructions to keep the data receiving device 120 and the multipurpose data receiving device 130 connected to a power source and in close proximity until the update is complete.

[0139] The data receiving device 120 or the sensor 110 receives the data for the update and a command to initiate the update from the multipurpose data receiving device 130. The data receiving device 120 may then install the firmware or software update. To install the update, the data receiving device 120 or the sensor 110 may place itself in a so-called "safe" mode with limited operational capabilities, or may reboot. Once the update is complete, the data receiving device 120 or the sensor 110 may re-enter a standard operating mode or be reset. The data receiving device 120 or the sensor 110 may perform one or more self-tests to determine that the firmware or software update was successfully installed. The multipurpose data receiving device 130 may receive notification of a successful update. The multipurpose data receiving device 130 may then report confirmation of the successful update to the remote application server 150.

[0140] In certain embodiments, the storage memory 5030 of the sensor 110 includes one-time programmable (OTP) memory. The term OTP memory may refer to memory that includes access restrictions and security to facilitate writing to specific addresses or segments within the memory a predetermined number of times. The memory 5030 may be pre-configured into multiple pre-allocated memory blocks or containers. The containers are pre-allocated to a fixed size. When the storage memory 5030 is one-time programmable memory, the containers may be considered to be in a non-programmable state. Additional containers that have not yet been written to may be in a programmable or writable state. Containerizing the storage memory 5030 in this manner may improve the transportability of code and data to be written to the storage memory 5030. Updating software of a device (e.g., a sensor device described herein) stored in OTP memory may be performed by replacing only the code in one or more specific previously written containers with updated code written to one or more new containers, rather than replacing the entire code in the memory. In a second embodiment, the memory is not pre-configured. Instead, the space allocated for data is dynamically allocated or determined as needed. Containers of various sizes can be defined in which updates are expected, allowing incremental updates to be issued.

[0141] 16 is a schematic diagram illustrating example operations and data flows for over-the-air (OTA) programming of storage memory 5030 in sensor device 100 and use of the memory after OTA programming in execution of a process by sensor device 110 in accordance with the disclosed subject matter. In the example of OTA programming 500 shown in FIG. 5, a request is sent from an external device (e.g., data receiving device 130) to initiate OTA programming (or reprogramming). At 511, a communications module 5040 of sensor device 110 receives the OTA programming command. The communications module 5040 transmits the OTA programming command to the microcontroller 5010 of sensor device 110.

[0142] At 531, after receiving the OTA programming command, the microcontroller 5010 verifies the OTA programming command. The microcontroller 5010 may, for example, determine whether the OTA programming command is signed with an appropriate digital signature token. Upon determining that the OTA programming command is valid, the microcontroller 5010 may place the sensor device in an OTA programming mode. At 532, the microcontroller 5010 may verify the OTA programming data. At 533, the microcontroller 5010 may reset the sensor device 110 to re-initialize the sensor device 110 to the programming state. Once the sensor device 110 transitions to the OTA programming state, the microcontroller 5010 may begin writing data to the rewritable memory 540 (e.g., memory 5020) of the sensor device at 534 and to the OTP memory 550 (e.g., storage memory 5030) of the sensor device at 535. The data written by the microcontroller 5010 may be based on the verified OTA programming data. The microcontroller 5010 may write data to mark one or more programming blocks or regions of the OTP memory 550 as invalid or inaccessible. The data written to the free or unused portions of the OTP memory may be used to replace the invalidated or inaccessible programming blocks of the OTP memory 550. After the microcontroller 5010 writes the data to the respective memories at 534 and 535, the microcontroller 5010 may perform one or more software integrity checks to ensure that no errors were introduced into the programming blocks during the writing process. Once the microcontroller 5010 determines that the data was written without error, the microcontroller 5010 may resume normal operation of the sensor device.

[0143] At 536, in execution mode, the microcontroller 5010 can retrieve a programming manifest or profile from the rewritable memory 540. The programming manifest or profile can include a list of valid software programming blocks and can include a guide to program execution for the sensor 110. By following the programming manifest or profile, the microcontroller 5010 can determine which memory blocks in the OTP memory 550 are appropriate to execute and can avoid executing outdated or invalidated programming blocks or referencing outdated data. At 537, the microcontroller 5010 can selectively retrieve memory blocks from the OTP memory 550. At 538, the microcontroller 5010 can use the retrieved memory blocks by executing programming code stored in the memory or by using variables stored in the memory.

[0144] As embodied herein, a first layer of security for communications between the analyte sensor 110 and other devices may be established based on a security protocol dictated by and integrated into the communications protocol used for communication. Another layer of security may be based on communications protocols requiring proximity of the communicating devices. Furthermore, certain packets and / or certain data contained within packets may be encrypted, while other packets and / or data within packets may be otherwise encrypted or unencrypted. Additionally or alternatively, application layer encryption may be used in conjunction with one or more block or stream ciphers to establish mutual authentication and communications encryption with other devices in the analyte monitoring system 100.

[0145] The ASIC 5000 of the analyte sensor 110 may be configured to dynamically generate authentication and encryption keys using data maintained in the storage memory 5030. The storage memory 5030 may also be pre-programmed with a set of valid authentication and encryption keys for use with a particular class of device. The ASIC 5000 may be further configured to perform an authentication process with the other device using the received data and apply a generated key to the sensitive data before transmitting the sensitive data. The generated key may be specific to the analyte sensor 110, specific to a pair of devices, specific to a communication session between the analyte sensor 110 and the other device, specific to a message sent during the communication session, or specific to a block of data contained within the message.

[0146] Both the sensor 110 and the data receiving device 120 may ensure the authentication of the other party in a communication session, for example, to issue commands or receive data. In certain embodiments, identity authentication may be performed through two mechanisms. First, the party asserting its identity provides a valid certificate signed by the device manufacturer or the operator of the analyte monitoring system 100. Second, authentication may be performed through the use of public and private keys established by the device in the analyte monitoring system 100 or by the operator of the analyte monitoring system 100, and a shared secret key derived from them. To verify the identity of another party, a party may provide proof that they have control of the private key.

[0147] The manufacturer of the analyte sensor 110, the data receiving device 120, or the provider of the application for the multi-purpose data receiving device 130 may provide the information and programming necessary for the devices to communicate securely through secure programming and updates. For example, the manufacturer may provide information that can be used to generate encryption keys for each device, including a secure root key for the analyte sensor 110 and optionally the data receiving device 120, which can be used in combination with device-specific information and operational data (e.g., entropy-based random values) to generate encryption values ​​unique to the device, session, or data transmission, as needed.

[0148] The analyte data associated with a user is, at least in part, sensitive data because this information can be used for a variety of purposes, including health monitoring and medication administration decisions. In addition to user data, the analyte monitoring system 100 may implement security enhancements against reverse engineering by external parties. Communication connections may be encrypted using device-specific or session-specific encryption keys. Encrypted or unencrypted communications between any two devices may be verified using transmission integrity checks built into the communications. The operation of the analyte sensor 110 may be protected from tampering by restricting access to read and write functions to the memory 5020 via the communication interface. The sensor may be configured to allow access only to known or "trusted" devices provided in a "whitelist," or to devices that can provide a predetermined code associated with the manufacturer or otherwise authenticated user. The whitelist may indicate an exclusive range, meaning that no connection identifiers other than those included in the whitelist may be used, or a preferred range, in which the whitelist is searched first but other devices may still be used. The sensor 110 may further reject a connection request and shut down if the requester fails to complete the login process over the communication interface within a predetermined time (e.g., within 4 seconds). These features protect against certain denial of service attacks, particularly those against BLE interfaces.

[0149] As embodied herein, analyte monitoring system 100 may use periodic key rotation to further reduce the likelihood of key compromise and misuse. The key rotation strategy employed by analyte monitoring system 100 may be designed to support backward compatibility for fielded or distributed devices. As an example, analyte monitoring system 100 may employ keys for downstream devices (e.g., devices in the field or unable to feasibly provide updates) that are designed to be compatible with multiple generations of keys used by upstream devices.

[0150] For purposes of illustration and not limitation, reference is made to an exemplary embodiment of a message sequence diagram 600 for use with the disclosed subject matter shown in FIG. 17 , illustrating an example of data exchange between a pair of devices, specifically a sensor 110 and a data receiving device 120. The data receiving device 120 may be a data receiving device 120 or a general-purpose data receiving device 130, as embodied herein. In step 605, the data receiving device 120 may send a sensor activation command 605 to the sensor 110, for example, via a short-range communication protocol. The sensor 110 may be primarily dormant prior to step 605, conserving its battery until full activation is required. After activation, during step 610, the sensor 110 may collect data or perform other operations as appropriate for the sensing hardware 5060 of the sensor 110. In step 615, the data receiving device 120 may initiate an authentication request command 615. In response to the authentication request command 615, both the sensor 110 and the data receiving device 120 may engage in a mutual authentication process 620. The mutual authentication process 620 may involve the transfer of data, including challenge parameters that allow the sensor 110 and the data receiving device 120 to ensure that the other device is capable of sufficient compliance with the agreed-upon security framework described herein. Mutual authentication may be based on a mechanism for authenticating two or more entities to each other, with or without an online trusted third party, to verify the establishment of a secret key via a challenge-response. Mutual authentication may be performed using two-pass, three-pass, four-pass, or five-pass authentication, or similar versions thereof.

[0151] Following a successful mutual authentication process 620, in step 625, the sensor 110 may provide a sensor secret 625 to the data receiving device 120. The sensor secret may include a sensor-specific value and may be derived from a random value generated during manufacturing. The sensor secret may be encrypted before or during transmission to prevent third parties from accessing the secret. The sensor secret 625 may be encrypted via one or more of the keys generated by or in response to the mutual authentication process 620. In step 630, the data receiving device 120 may derive a sensor-specific encryption key from the sensor secret. The sensor-specific encryption key may further be session-specific. Thus, the sensor-specific encryption key may be determined by each device without being transmitted between the sensor 110 or the data receiving device 120. In step 635, the sensor 110 may encrypt the data included in the payload. In step 640, using the appropriate communication model of the sensor 110 and the communication link established between the data receiving device 120, the sensor 110 may transmit the encrypted payload 640 to the data receiving device 120. In step 645, the data receiving device 120 may decrypt the payload using the sensor-specific encryption key derived during step 630. Following step 645, the sensor 110 may deliver additional (including newly collected) data, and the data receiving device 120 may process the received data appropriately.

[0152] As described herein, the sensor 110 may be a device with limited processing power, battery supply, and storage. The encryption technique (e.g., selection of a cryptographic algorithm or algorithm implementation) used by the sensor 110 may be selected based at least in part on these limitations. The data receiving device 120 may be a more powerful device with fewer limitations of this nature. Thus, the data receiving device 120 may employ more sophisticated and computationally intensive encryption techniques, such as cryptographic algorithms and implementations.

[0153] The analyte sensor 110 may be configured to modify its discoverability behavior to increase the probability that a receiving device will receive an appropriate data packet and / or provide a response signal, or to otherwise attempt to reduce limitations that may prevent a response signal from being received. Modifying the discoverability behavior of the analyte sensor 110 may include, for example, without limitation, modifying the frequency at which connection data is included in data packets, modifying the frequency at which data packets are generally transmitted, lengthening or shortening the broadcast window of data packets, modifying the time after broadcast at which the analyte sensor 110 will accept a response or scan signal, including direct transmissions to one or more devices that previously communicated with the analyte sensor 110 (e.g., via one or more attempted transmissions) and / or one or more devices on a whitelist, modifying the transmit power associated with the communications module when broadcasting a data packet (e.g., to increase the range of the broadcast or reduce energy consumed and extend the battery life of the analyte sensor), modifying the rate at which data packets are prepared and broadcast, or a combination of one or more other modifications. Additionally or alternatively, the receiving device may also adjust parameters related to the device's listening behavior to increase the likelihood of receiving data packets containing connection data.

[0154] As embodied herein, the analyte sensor 110 may be configured to broadcast data packets using two types of windows. The first window indicates the rate at which the analyte sensor 110 is configured to operate its communications hardware. The second window indicates the rate at which the analyte sensor 110 is configured to actively transmit (e.g., broadcast) data packets. As an example, the first window may indicate that the analyte sensor 110 operates its communications hardware to transmit and / or receive data packets (including connection data) during the first two seconds of each 60-second period. The second window may indicate that the analyte sensor 110 transmits a data packet every 60 milliseconds during each two-second window. The remainder of the time during the two-second window, the analyte sensor 110 is scanning. The analyte sensor 110 may lengthen or shorten either window to change the discoverability behavior of the analyte sensor 110.

[0155] In certain embodiments, the discoverability behavior of the analyte sensor can be stored in a discoverability profile and can be modified based on one or more factors, such as the state of the analyte sensor 110, and / or by applying rules based on the state of the analyte sensor 110. For example, when the battery level of the analyte sensor 110 falls below a certain amount, a rule may cause the analyte sensor 110 to reduce the power consumed by the broadcast process. As another example, configuration settings associated with broadcasting or otherwise transmitting packets may be adjusted based on the ambient temperature, the temperature of the analyte sensor 110, or the temperature of a particular component of the analyte sensor's 110 communications hardware. In addition to modifying transmission power, other parameters related to the transmission capabilities or processes of the analyte sensor's 110 communications hardware can be modified, including, but not limited to, transmission rate, frequency, and timing. As another example, when analyte data indicates that a subject is experiencing or is about to experience a negative health event, a rule may cause the analyte sensor 110 to increase its discoverability in order to alert receiving devices of the negative health event.

[0156] As embodied herein, certain calibration mechanisms for the sensing hardware 5060 of the analyte sensor 110 may be adjusted based on external or interval environmental characteristics and to compensate for decay of the sensing hardware 5060 during periods of non-use (e.g., "storage time" before use). The calibration mechanisms of the sensing hardware 5060 may be adjusted autonomously by the sensor 110 (e.g., by operation of the ASIC 5000 to alter characteristics in memory 5020 or storage 5030) or may be adjusted by other devices in the analyte monitoring system 100.

[0157] As an example, the sensor sensitivity of the sensing hardware 5060 may be adjusted based on external temperature data or time since manufacture. When external temperature is monitored during sensor storage, the disclosed subject matter may adaptively change compensation for sensor sensitivity over time as the device experiences changing storage conditions. By way of example and not limitation, adaptive sensitivity adjustment may be performed in an “active” storage mode in which the analyte sensor 110 periodically wakes up to measure temperature. These mechanisms may conserve the battery of the analyte device and extend the life of the analyte sensor. At each temperature measurement, the analyte sensor 110 may calculate a sensitivity adjustment for that period based on the measured temperature. The temperature-weighted adjustment value may then be accumulated over the active storage mode period to calculate a total sensor sensitivity adjustment value at the end of the active storage mode (e.g., upon insertion). Similarly, upon insertion, the sensor 110 may determine the time difference between the manufacture of the sensor 110 (which can be written to the storage 5030 of the ASIC 5000) or the sensing hardware 5060 and alter the sensor sensitivity or other calibration mechanisms according to one or more known attenuation rates or formulas.

[0158] Additionally, for purposes of illustration and not limitation, as embodied herein, the sensor sensitivity adjustment may account for other sensor conditions, such as sensor drift. For example, in the case of sensor drift, the sensor sensitivity adjustment may be hard-coded into the sensor 110 during manufacturing based on an estimate of how much the average sensor will drift. The sensor 110 may use a calibration function having time-varying functions for sensor offset and gain, which may account for drift over the period of sensor wear. Thus, the sensor 110 may utilize a device-dependent function that describes the sensor 110's drift over time, and utilize a function used to convert interstitial current to interstitial glucose, which may indicate sensor sensitivity and may be device-specific in combination with a baseline glucose profile. Such a function to account for sensor sensitivity and drift may improve the accuracy of the sensor 110 over the period of wear without user calibration.

[0159] The sensor 110 detects raw measurements from the sensing hardware 5060. On-sensor processing may be performed, such as by one or more models trained to interpret the raw measurements. The models may be machine learning models trained off-device to detect, predict, or interpret the raw measurements to detect, predict, or interpret the levels of one or more analytes. Additional trained models may operate on the output of the machine learning models trained to interact with the raw measurements. As an example, a model may be used to detect, predict, or recommend an event based on the raw measurements and the type of analyte(s) detected by the sensing hardware 5060. Events may include the initiation or completion of physical activity, a meal, the application of a medical procedure or medication, an emergency health event, and other events of a similar nature.

[0160] The model may be provided to the sensor 110, data receiving device 120, or multipurpose data receiving device 130 during manufacturing or during a firmware or software update. The model may be periodically refined, for example, by the sensor 110 manufacturer or the operator of the analyte monitoring system 100, based on data received from the sensor 110 and data receiving device of an individual user or multiple users collectively. In certain embodiments, the sensor 110 includes sufficient computational components to support further training or refinement of the machine learning model, such as based on unique characteristics of the user to which the sensor 110 is attached. Machine learning models may include, by way of example and not limitation, models trained using or incorporating decision tree analysis, gradient boosting, ADA boosting, artificial neural networks or variants thereof, linear discriminant analysis, nearest neighbor analysis, support vector machines, supervised or unsupervised classification, etc. Models may also include algorithmic or rule-based models in addition to machine learning models. Model-based processing may be performed by other devices, including the data receiving device 120 or multipurpose data receiving device 130, upon receiving data from the sensor 110 (or other downstream devices).

[0161] The data transmitted between the sensor 110 and the data receiving device 120 may include raw measurements or processed measurements. The data transmitted between the sensor 110 and the data receiving device 120 may further include alarms or notifications for display to a user. The data receiving device 120 may display or otherwise convey notifications to a user based on the raw measurements or processed measurements, or may display alarms as received from the sensor 110. Alarms that may be triggered for display to a user include alarms based on direct analyte values ​​(e.g., a single reading that exceeds or does not meet a threshold), analyte value trends (e.g., average readings over a set period of time that exceed or do not meet a threshold, slope), analyte value predictions (e.g., algorithmic calculations based on analyte values ​​that exceed or do not meet a threshold), sensor alerts (e.g., a detected suspected failure), communication alerts (e.g., no communication between the sensor 110 and the data receiving device 120 for a threshold period of time, an unknown device attempting to initiate or failing to initiate a communication session with the sensor 110), reminders (e.g., a reminder to charge the data receiving device 120, take medication, or perform other activities), and other alerts of a similar nature. By way of example and not limitation, as embodied herein, the alarm parameters described herein may be configurable by the user, may be fixed during manufacturing, or may be a combination of user-configurable and non-user-configurable parameters.

[0162] According to aspects of the disclosed subject matter, an in-vivo analyte sensor and method for determining the accuracy of a detected alcohol level is provided. For example, embodiments disclosed herein can help improve quality control of analyte sensors, thereby ensuring that the detected alcohol level is representative of the wearer's blood alcohol concentration (BAC).

[0163] As used herein, the term "alcohol" and grammatical variations thereof refer to any primary, secondary, or tertiary alcohol. For example, the alcohol sensor of the present disclosure can detect ethanol, methanol, butanol, propanol, isopropyl alcohol, etc., and any combination thereof.

[0164] As used herein, the term "reference electrode" can refer to a reference electrode or an electrode that functions as both a reference electrode and a counter electrode. Similarly, as used herein, the term "counter electrode" can refer to both a counter electrode and a counter electrode that also functions as a reference electrode.

[0165] The sensor 110 described herein can include a sensing element including one or more electrodes configured to detect one or more analyte levels in a bodily fluid, examples of which are shown in FIGS. 18A-20. The one or more electrodes can include one or more enzyme-responsive elements. For example, as embodied herein, the sensor 110 can detect alcohol levels in a bodily fluid. In another example, the sensor 110 can detect alcohol and glucose levels in a bodily fluid. In yet another example, the sensor 110 can detect alcohol and ketone levels in a bodily fluid. The sensor 110 can include one working electrode capable of detecting alcohol and / or another working electrode capable of detecting glucose, ketone, lactate, and / or any other analyte levels. In some examples, the sensor 110 can include two or more sensing elements configured to detect two or more analyte levels in a bodily fluid. The sensor 110 can also be referred to as an "analyte sensor."

[0166] An individual's in vivo alcohol concentration can vary dramatically based on alcohol intake or various physiological factors. For example, alcohol may be metabolized at different rates by different individuals, which can lead to varying alcohol levels among individuals consuming the same amount of alcohol per body weight. The equilibrium concentration of alcohol depends at least on water content, blood flow rate, and body weight. Given that alcohol crosses biological membranes, alcohol can flow from the bloodstream to all tissues and fluids. The flow rate can be proportional to the water content of the tissues and fluids. Furthermore, as described above, alcohol concentration can affect the function of one or more other analytes in an individual, thereby affecting the individual's health or physiological condition. For example, any of the sensor systems and analyte sensor configurations described below can feature one or more enzymes used to detect alcohol.

[0167] Ex vivo alcohol measurements can be performed by taking a physical blood sample, urine sample, saliva sample, sweat or perspiration sample, or breath test. However, these measurements are static in time and may reflect erroneous or inaccurate results in some cases. Analyte sensors, on the other hand, are dynamic and are updated over time. Alcohol sensors respond to in vivo alcohol levels and can provide "continuous" measurements. Alcohol sensors can provide multiple alcohol concentration measurements over continuous periods, such as seconds, minutes, or hours to days, weeks, or months.

[0168] An individual wearing a continuous alcohol sensor can access real-time alcohol level information and make various decisions based thereon, such as whether to operate a vehicle and / or whether levels of other analytes, such as glucose, are dysregulated based on the alcohol level. For example, alcohol sensors can be used to monitor, test, and / or assess alcohol levels in individuals suffering from alcohol abuse, dependence, or addiction. Alcohol levels can be monitored by the individual themselves, by a medical professional, or by a law enforcement professional.

[0169] A display unit of the sensor or reader device can be used to provide instructions, suggestions, guidance, recommendations, and / or any other output associated with or corresponding to the alcohol concentration. Appropriate processing algorithms, processors, memory, electronic components, etc. can reside in either a trusted computer system, a remote terminal, a cloud server, the reader device, and / or the housing of the sensor itself. The guidance, recommendations, output, and / or the like can be shown on a display unit or graphical user interface that is in electronic communication with the sensor or one or more components of the sensor system. The display unit or device can be a dedicated reader device or user equipment such as a mobile device. Alternatively, the display unit or device can be a third-party server, cloud server, or remote terminal that communicates with various software applications that can be accessed by a medical professional. One of the dedicated reader device, user equipment, or server can further relay the data or output to one or more secondary devices, such as a smart home device, a wearable watch or device, a personal health monitor, etc.

[0170] As embodied herein, a reader device may include a processor, memory, an input / output interface, and a communication interface. The processor includes hardware for executing instructions, such as those comprising a computer program. By way of example and not limitation, to execute instructions, a processor may retrieve (or fetch) instructions from an internal register, an internal cache, memory, or storage, decode and execute them, and then write one or more results to an internal register, an internal cache, memory, or storage. The processor may also include one or more internal caches for data, instructions, or addresses. The one or more processors may include one or more arithmetic logic units (ALUs) or may be multi-core processors.

[0171] As embodied herein, memory includes a main memory for storing instructions for a processor to execute or data for a processor to operate on. By way of example and not limitation, a reader device may load instructions into memory from storage or another source. The processor may then load the instructions from memory into an internal register or internal cache. To execute the instructions, the processor may retrieve the instructions from the internal register or internal cache and decode them. During or after executing the instructions, the processor may write one or more results (which may be intermediate or final results) to the internal register or internal cache. The processor may then write one or more of the results to memory. For example, the memory may include a random access memory (RAM). This RAM may be a volatile memory, a dynamic RAM (DRAM), or a static RAM (SRAM). The RAM may be a single-ported or multi-ported RAM, and the memory may include one or more memories.

[0172] As described herein with reference to FIG. 1A , the sensor 110 can be at least partially inserted into the dermis or subcutaneous layer of the skin. The sensor 110 can include a sensor tail of sufficient length to insert to a desired depth within the interstitial fluid. The sensor tail can include at least one working electrode and one or more active areas (sensing areas / spots or sensing layers) disposed thereon that are active for detecting alcohol (or optionally one or more additional analytes). For example, the active areas can be in the form of one or more separate spots. The number of separate spots can range, for example, from 1 to 12 spots. The one or more separate spots can have an area of ​​approximately 0.01 square millimeters (mm ). 2 ) ~ approx. 1.00 mm 2 , for example, about 0.1 mm 2 ~about 0.5mm 2 , about 0.25mm 2 ~about 0.75mm 2 , about 0.05mm 2 ~approx. 0.2 mm 2 or may have any other smaller or larger value.

[0173] One or more active regions can include one or more enzymes used to facilitate the detection of alcohol. The active region can include, for example, a polymeric material to which one or more enzymes are chemically bonded (e.g., covalently, ionically, etc.) or otherwise immobilized (e.g., not bound in a matrix). For example, each active region can be coated with a substance-limiting biocompatible membrane and / or an electron transfer agent to facilitate at least the detection of alcohol.

[0174] As embodied herein, alcohol levels may be monitored in any biological fluid of a subject, such as skin fluid, interstitial fluid, plasma, blood, lymphatic fluid, synovial fluid, cerebrospinal fluid, saliva, bronchoalveolar lavage, or amniotic fluid.

[0175] As shown in FIG. 1A , the sensor control unit 102 can manually or automatically transfer data acquired by the sensor 110 to the reader device 120. For example, alcohol concentration data may be communicated automatically or periodically after a specific period of time has elapsed, with the data stored in memory until transmission (e.g., every few seconds, every minute, every five minutes, or other predetermined period of time). The sensor control unit 102 can also communicate with the reader device 120 according to an unscheduled schedule based on the wearer's or user's actions or requests. For example, data can be communicated from the sensor control unit 102 using NFC or RFID technology when the sensor electronics are brought within communication range of the reader device 120. Additionally or alternatively, Bluetooth® can be used to facilitate communication of data from the sensor control unit 102 to the reader device 120. The data can remain stored in the memory of the sensor control unit 102 until it is communicated to the reader device 120. In one example, data can be stored in the memory of the sensor control unit 102 for up to eight hours. In other examples, the data may be stored for up to 0.5 hours, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 10 hours, 12 hours, 24 hours, or any other period of time. The data may then be transmitted from the sensor control device 102 to the reader device 120 when the sensor control device 102 is within a given distance from the reader device 120.

[0176] For purposes of illustration and not limitation, an exemplary alcohol sensor, as embodied herein, can feature active regions located on one or both sides of a single working electrode, or on one or both sides of two or more separate working electrodes. In other examples, an alcohol sensor can use one or more working electrodes and one or more other electrodes, such as a reference electrode. Sensor configurations having a single working electrode are described below with reference to FIGS. 18A-18C. Each of these sensor configurations can suitably incorporate one or more alcohol-responsive active regions. Sensor configurations having multiple working electrodes are described below with reference to FIGS. 19 and 20. When multiple working electrodes are present, one or more alcohol-responsive active regions can be disposed on one or more of the multiple working electrodes, and the one or more working electrodes can be used to detect another analyte of interest in coordination with alcohol level detection.

[0177] When a single working electrode is included in an alcohol sensor, a counter electrode and a reference electrode may also be included. Thus, the alcohol sensor may include a total of three electrodes along with the single working electrode. For example, the alcohol sensor may include a working electrode and a second electrode, such as a counter electrode or a reference electrode. In one example, the counter electrode and the reference electrode may be combined into a single second electrode. In examples including two or three electrodes, one or more active regions of the alcohol sensor may be in contact with the working electrode. The one or more active regions may include, for example, one or more enzymes.

[0178] The various electrodes may be at least partially stacked or layered on one another. For example, the various electrodes may be laterally spaced apart from one another on the sensor tail. Similarly, the associated active areas on each electrode may be vertically stacked on top of one another or may be laterally spaced apart. The various electrodes may be electrically isolated from one another by a dielectric material or similar insulator.

[0179] FIG. 18A is a cross-sectional schematic diagram illustrating an exemplary analyte sensor including a single active area as embodied herein. For example, FIG. 18A illustrates a two-electrode sensor configuration. The analyte sensor illustrated in FIG. 18A can detect, for example, at least alcohol levels. The sensor 1800 of FIG. 18A can be similar to the sensor 110 illustrated in FIG. 1A. The sensor 1800 can include a substrate 1812 disposed between a working electrode 214 and a counter / reference electrode 1816. In some examples, the working electrode 1814 and the counter / reference electrode 1816 can be disposed on the same side (e.g., top or bottom) of the substrate 1812, with a dielectric material interposed therebetween. The active area 1818 can be disposed as one or more layers on a portion of the working electrode 1814. Furthermore, the active area 1818 can include a single spot or multiple spots configured for detection of one or more analytes of interest. One or more enzymes can be present on a single spot or multiple spots of the active area 1818.

[0180] 18A , a membrane 1820 can cover at least the active area 1818. The membrane 1820 can also cover part or all of the working electrode 1814, the counter / reference electrode 1816, or the entire analyte sensor 1800. One or both sides of the analyte sensor 1800 can be covered by the membrane 1820. The membrane 1820 can include one or more polymeric membrane materials that can limit analyte flux to the active area 1818. For example, the sensor 1800 can assay alcohols by using at least one of coulometry, amperometry, voltammetry, potentiometry electrochemistry, or iontophoresis (including reverse iontophoresis) detection.

[0181] FIG. 18B is a cross-sectional schematic diagram illustrating an exemplary analyte sensor including a single active region as embodied herein. FIG. 18C is a cross-sectional schematic diagram illustrating an exemplary analyte sensor including a single active region as embodied herein. For example, FIGS. 18B and 18C illustrate a three-electrode sensor configuration. Both FIGS. 18B and 18C show a working electrode 1814, a counter or reference electrode 1816, and an additional electrode 1817. The additional electrode 1817 can be either a separate counter / reference electrode or a separate working electrode. The additional electrode 1817 can be disposed on either the working electrode 1814 or the counter / reference electrode 1816, with a separating layer of dielectric material disposed therebetween. As shown in FIG. 18B, dielectric layers 1819a, 1819b, and 1819c separate the electrodes 1814, 1816, and 1817 from one another to provide electrical insulation. 18C, at least one of electrodes 1814, 1816, and 1817 can be disposed on opposite sides of substrate 1812. Thus, working electrode 1814 and counter electrode 1816 can be disposed on opposite sides of substrate 1812, with reference electrode 1817 disposed on one of electrodes 1814 or 1816 and spaced therefrom by a dielectric material.

[0182] As embodied herein, working electrode 1814 and reference electrode 1816 can be disposed on opposite sides of substrate 1812, with counter electrode 1817 disposed on one of electrodes 1814 or 1816 and separated therefrom by a dielectric material. In yet another embodiment, reference electrode or counter electrode 1816 can be disposed on one side of substrate 1812, and working electrode 1814 can be disposed on the opposite side. Reference material layer 1830, which can be composed of silver (Ag) or silver chloride (AgCl), can be present on electrode 1817. Reference material layer 1830 can be disposed in any other location on electrode 1817, electrode 1814, or electrode 1816.

[0183] 18B and 18C, analyte sensors 1801 and 1802 can include one or more enzymes within active area 1818. As embodied herein, active area 1818 can include a single area configured to detect at least alcohol. Additionally or alternatively, active area 218 can include two or more areas, each configured for the detection of alcohol, or each configured for the detection of a different analyte of interest, including alcohol. Analyte sensors 1801 and 1802 can assay alcohol, or one or more additional analytes, for example, by coulometric, amperometric, voltammetric, potentiometric electrochemical, or iontophoretic detection techniques.

[0184] Continuing with reference to FIGS. 18B and 18C, a membrane 1820 can cover the active area 1818 and other sensor components in sensors 1801 and 1802. An additional electrode 1817 can also be covered with membrane 1820. While FIGS. 18B and 18C show electrodes 1814, 1816, and 1817 all covered with membrane 1820, in other examples, only the working electrode 1814 can be covered, or only the working electrode 1814 and one other electrode can be covered. The thickness of membrane 1820 on each of electrodes 1814, 1816, and / or 1817 can be the same or different. For example, the surface area covered by membrane 1820 on each of electrodes 1814, 1816, and / or 1817 can be the same or different. One or both sides of analyte sensors 1801 and 1802 may be coated with membrane 1820. Alternatively, analyte sensors 1801 and 1802 may be coated entirely.

[0185] FIG. 19 is a cross-sectional schematic diagram illustrating an exemplary analyte sensor including two active regions embodied herein. As shown in FIG. 19, the alcohol sensor 1900 has two working electrodes, a reference electrode, and a counter electrode. The sensor 1900 includes working electrodes 304 and 306 disposed on opposite sides of a substrate 1902. An active region 1910 is disposed on the surface of the working electrode 1904, and an active region 1912 is disposed on the surface of the working electrode 1906. One or more enzymes configured to detect alcohol may be present within the active regions 1910 and 1912. For example, one or more of the active regions 1910 or 1912 may be configured to detect alcohol concentration and another analyte of interest, such as glucose, lactate, or ketones. The counter electrode 1920 may be electrically insulated from the working electrode 1904 by a dielectric layer 1922, and the reference electrode 1921 may be electrically insulated from the working electrode 1906 by a dielectric layer 1923. Outer dielectric layers 1930 and 1932 are disposed on reference electrode 1921 and counter electrode 1920, respectively. A membrane 1940 can cover at least active areas 1910 and 1912. Other components of analyte sensor 1900 can be coated with membrane 1940, and / or one or both sides of analyte sensor 1900, or portions thereof, can be coated with membrane 1940. Similar to analyte sensors 1800, 1801, and 1802 shown in FIGS. 18A-18C, sensor 1900 can be operable to assay one or more target analytes, including alcohols, by coulometric, amperometric, voltammetric, potentiometric electrochemical, or iontophoretic techniques, or any other suitable assay technique.

[0186] As embodied herein, alternative sensor configurations different from that shown in Figure 19 can include multiple working electrodes and a combined counter / reference electrode instead of separate counter electrode 1920 and reference electrode 1921. In other examples, the arrangement of counter electrode 1920 and reference electrode 1921 can be reversed from that shown in Figure 19. Additionally, working electrodes 1904 and 1906 can be positioned on the same side of substrate 1902.

[0187] 18A-18C and 19 are described herein as analyte sensor configurations having one or two working electrodes, in other examples, the analyte sensor can include three or more working electrodes. The additional working electrodes can provide additional active areas and corresponding sensing capabilities.

[0188] Furthermore, although FIGS. 18A-18C and 19 depict analyte sensors having planar (e.g., substantially flat) substrates including electrodes and active regions disposed thereon, the analyte sensors can have other shapes and configurations. For example, without limitation, the substrate can be substantially non-planar (e.g., curved, hemispherical, or spherical), cylindrical, spiral, other irregular, or any combination thereof. Similarly, one or more electrodes can be substantially non-planar (e.g., relatively curved, hemispherical, or spherical), cylindrical, spiral, other irregular, or any combination thereof. The electrodes can be arranged in layers, concentric circles, or any other configuration. The sensing region disposed on the working electrode can cover at least a portion of the working electrode as a single layer or as separate regions of various shapes, such as square, circular, semicircular, arcuate, rectangular, polygonal, or other irregular shapes.

[0189] As embodied herein, an electron transfer agent can be present in one or more of the active regions of an alcohol sensor. The electron transfer agent can serve to facilitate the transport of electrons to the working electrode, including when the alcohol analyte undergoes a redox reaction. The electron transfer agent in each active region can determine the redox potential observed for the alcohol analyte.

[0190] FIG. 20 is a cross-sectional schematic diagram illustrating an exemplary analyte sensor including two active regions as embodied herein. The analyte sensor configuration of FIG. 20 can be similar to FIG. 18C , which includes two active regions 2018a and 2018b. As shown in FIG. 20 , analyte sensor 2000 includes active regions 2018a and 2018b on the surface of working electrode 2014. Active region 2018a includes a first electron transfer agent and a first analyte-responsive enzyme bound to active region 2018a. Active region 2018b similarly includes a second electron transfer agent and a second analyte-responsive enzyme bound to active region 2018b. As embodied herein, the first and second electron transfer agents can differ in composition to provide separation of the redox potentials of first active region 2018a and second active region 2018b. For example, active region 2018b may comprise an alcohol-responsive enzyme such as ketone reductase, while active region 2018a can comprise a glucose-responsive enzyme such as glucose oxidase.

[0191] The redox potentials of the first active region 2018a and the second active region 2018b can be sufficiently separated to allow a first independent signal to be generated by the first active region 2018a and a second independent signal to be generated by the second active region 2018b. Thus, the analyte sensor 2000 can operate at a first potential at which a redox reaction occurs in the first active region 2018a but not in the second active region 2018b. A first analyte, such as glucose, can be selectively detected at or above the redox potential of the first active region 2018a, provided that the applied potential is not high enough to promote a ketone reductase reaction with the second active region 2018b. The concentration of the first analyte can be determined from the generated signal by referencing a lookup table or calibration curve.

[0192] Similarly, the redox potential of the second active region 2018b can occur simultaneously or nearly simultaneously in both the first active region 2018a and the second active region 2018b. As a result, a signal generated above the redox potential of the second active region 2018b can comprise a composite signal having signal contributions from both the first active region 2018a and the second active region 2018b. To determine the concentration of a second analyte, such as asalcohol, from the composite signal, the signal from the first active region 2018a above the corresponding redox potential can be subtracted from the composite signal to provide a difference signal associated with only the second active region 2018b. Once the difference signal associated with the second active region 2018b is determined, a lookup table or calibration curve can be used to determine the concentration of the second analyte.

[0193] The active region of an alcohol sensor can be based, for example, on X7-wired diaphorase bound to ketone reductase (KRED) by allowing free diffusion of nicotinamide-adenine dinucleotide phosphate (NADP) trapped within the sensing layer. Such active regions may exhibit low enzymatic activity, improving sensor performance. Low enzymatic activity can be, for example, about 10 to about 10,000 times lower than that of a normally functioning analyte sensor. For active regions with low enzymatic activity, the enzyme's inherent thermostability can have an increasingly significant effect on the rendered signal. For example, under conditions of low enzymatic activity, it can be difficult to compensate for enzymatic instability by increasing the enzyme loading. This makes it difficult to obtain a stable signal over the sensor's implantation period and / or shelf life. To compensate for low enzymatic activity, some examples utilize redox mediators that can operate at low enzyme potentials and / or other mechanisms that help amplify or stabilize the signal. The implantation period can be several hours, days, weeks, or months. For example, the implantation period can range from 2 hours to 14 days.

[0194] In an exemplary embodiment, the sensor control device 102, which may also be referred to as an on-body patch device, can include one or more temperature sensors. The one or more temperature sensors can detect body temperature. A temperature below a temperature threshold can indicate that the test substance sensor is no longer properly positioned on the wearer. The threshold temperature can be, for example, 97.9°F (36.6°C), any value between about 95.0°F (35.0°C) and about 103°F (39.4°C), such as 97.5°F (36.4°C) and 96.8°F (36.0°C), or any other value. The threshold temperature can be predetermined or measured during an initial wear period of the test substance sensor. The initial wear period can be, for example, 1 hour, 2 hours, 3 hours, 6 hours, 12 hours, 1 day, 2 days, 3 days, 7 days, and / or any other number of minutes, hours, or days. When one or more temperature sensors detect a temperature below the threshold body temperature after a specified wearing period, an indication, notification, alarm, or alert may be triggered on the reader device 120. The indication, notification, alarm, or alert may be triggered when the detected temperature is 2.5°F (-16.4°C), 2.0°F (-16.7°C), 1.5°F (-16.9°C), 1.0°F (-17.2°C), 0.5°F (-17.5°C), 0.1°F, or any other value below the threshold temperature. In other examples, the indication, notification, alarm, or alert may be triggered when the temperature drops 1, 2, or 3 standard deviations below the threshold temperature.

[0195] The indication, notification, alarm, or alert may be, for example, audible, vibratory, or visual. In some examples, a detected drop in temperature may trigger an indication, notification, alarm, or alert in remote application server 150. Remote application server 150 may be accessed by the sensor wearer, a medical professional, and / or any other party, such as a law enforcement professional.

[0196] One or more temperature sensors may, in some examples, be used for multiple determinations by the sensor control device 102. For example, as described above, one or more temperature sensors may be used to determine when a detected body temperature drops below a threshold temperature after a particular wear period. In another example, one or more temperature sensors may be used to determine when a detected body temperature rises above a threshold temperature after a particular wear period. The same one or more temperature sensors may also detect the temperature of an analyte sensor. The detected temperature or analyte sensor may be used, in part, to determine a BAC level. In other examples, different one or more temperature sensors are used to determine body temperature and analyte sensor temperature.

[0197] In an exemplary embodiment, the sensor control device 102 can include analyte sensors having one or more enzyme-responsive elements capable of detecting alcohol levels, such as ethanol levels, and one or more other analyte levels, such as glucose levels, lactate levels, or ketone levels, as shown in Figures 18A-20. For example, a single sensor can be used to detect alcohol levels and one or more other analyte levels. When a single sensor is used to detect alcohol levels and one or more other analyte levels, two or more active areas can be used, as shown in Figures 19 and 20, for example.

[0198] In embodiments where the detected alcohol level and one or more other analyte levels are zero or about zero, the analyte sensor may be improperly placed on the wearer. When the detected alcohol level is about zero but one or more other analyte levels are greater than about zero, this may indicate that the analyte sensor is properly placed or that an error has occurred in the sensor used to detect the alcohol level. For example, when the detected ethanol level is about zero and the detected glucose level is either about zero or greater than about zero, this may indicate that the alcohol sensor is experiencing an adverse condition. An adverse condition may occur, for example, when the analyte sensor is improperly placed, removed, or mispositioned and / or when the analyte sensor is malfunctioning or experiencing an error. An instruction, notification, alarm, or alert may then be triggered to notify the wearer or any other person of the improper placement or error of the analyte sensor.

[0199] In an example embodiment, a threshold or background signal can be detected by an analyte sensor, examples of which are shown in Figures 18A-20. The threshold or background signal can be, for example, the noise level generated by the analyte sensor. The threshold or background signal can be due to one or more oxidizable compounds (e.g., ascorbate, urate, or sulfur compounds) detected by one or more active regions. An example threshold or background signal level 506 is shown in Figure 21. Figure 21 is a graph showing the current output of an exemplary analyte sensor embodied herein. For example, Figure 21 shows the current output 2104 of an ethanol sensor 2102 over a two-week period. As shown in Figure 21, the threshold or background signal level can be approximately 1000 picoamps on days 1-3 (9 / 21-9 / 23), then linearly decreasing to approximately 500 picoamps on day 14 (10 / 4). The threshold or background signal level can decrease, for example, linearly or nonlinearly, during at least a portion of the analyte sensor's life. The threshold or background signal level can also increase, for example, linearly or nonlinearly, during at least a portion of the analyte sensor's life. The threshold or background signal level can stabilize or equilibrate after an initial wearing period. The initial wearing period can be, for example, 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days.

[0200] Further, with reference to FIG. 21 , as embodied herein, the amplitude of a detected analyte level, such as a detected alcohol level, may decrease below the amplitude of a threshold or background signal level, which may indicate either an error in the analyte sensor or that the analyte sensor is improperly positioned. The threshold or background signal level may decrease or include, for example, a linear or nonlinear decrease during at least a portion of the analyte sensor's lifespan. In this manner, the threshold or background signal level may be determined during the initial wear period of the analyte sensor, the entire wear period of the analyte sensor, or any period therebetween. Additionally or alternatively, variations in one or more other signal output parameters may be used. The signal output may be, for example, current, voltage, charge, energy, potential, potential difference, or any other signal output.

[0201] When the amplitude or any other signal parameter of the detected signal falls below a threshold or background signal level, an indication, notification, alarm, or alert may be triggered. The detected signal may, for example, be at least 1, 2, or 3 standard deviations below the threshold or background signal. In another example, the detected signal may be below the threshold or background signal by more than a given percentage. For example, the detected signal may be 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, or any other percentage value below the threshold or background signal. Any other measure for determining that the detected signal is below the background or threshold signal may be used.

[0202] In addition to or instead of utilizing the detected signal amplitude, in one example embodiment, a variation in threshold or background signal amplitude over a period of time may be utilized. The predetermined period may be, for example, 3 hours, 6 hours, 12 hours, 24 hours, or any other period of time. As described above, the threshold or background signal level may decrease or include a linear or nonlinear decrease during at least a portion of the analyte sensor's lifetime. For example, the threshold or background signal level may decrease by 50% or more over the analyte sensor's lifetime. Thus, a deviation or variation of more than 50%, meaning an increase or decrease of more than 50%, may indicate an error in the analyte sensor, such as improper placement of the sensor or another sensor failure. Any other variation, such as 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, or any other percentage, may be used to determine the variation. The percentage may be predetermined, for example. The predetermined percentage may be based on the sensitivity of the analyte sensor tested during the manufacture of one or more sensor batches. Thus, a predetermined percentage may correspond to a given production batch. When the threshold or background signal variation exceeds the percentage, an indication, notification, alert, or alarm may be output.

[0203] The background or threshold drift may vary over the life of the analyte sensor, for example, as shown in FIG. 21 . The background or threshold drift may vary over a portion of the life of the analyte sensor or over the entire life of the analyte sensor. During the initial wear period, e.g., the first three, four, or five days after sensor implantation, the drift may be smaller or larger than during the remainder of the sensor's life. Thus, determining the drift during the initial wear period may include using a higher or lower drift percentage than during the remainder of the wear period. For example, the drift during the initial wear period may be 40%, while the drift during the remainder of the wear period may be 10%. Thus, a drift of more than 40% during the initial wear period and / or a drift of more than 10% during the remainder of the wear period may indicate an adverse condition of the analyte sensor, such as a malfunction of the analyte sensor or an improperly positioned analyte sensor.

[0204] 22A-22D are graphs illustrating background signals of exemplary analyte sensors embodied herein. In particular, FIGS. 22A-22D illustrate a first sensor 2210, a second sensor 2220, a third sensor 2230, and a fourth sensor 2240, each having a background signal 2212, 2222, 2232, and 2242, respectively. For example, the background signals 2212 and 2242 on day 1 (11 / 30) may be approximately 400 picoamps, while the background signal on day 8 (12 / 7) may be approximately 200 picoamps. In another example, the background signal 2222 on day 1 (11 / 30) may be approximately 400 picoamps, while the background signal on day 8 (12 / 7) may be approximately 350 picoamps. Meanwhile, the background signal 2232 on day 1 (11 / 30) may be approximately 500 picoamps, while the background signal on day 8 (12 / 7) may be approximately 150 picoamps.

[0205] By way of example and not limitation, a decrease or drop in signal amplitude can indicate an error in the analyte sensor and / or improper placement of the analyte sensor. For example, as embodied herein, a sudden decrease or drop in signal amplitude can indicate an adverse condition of the analyte sensor. A sudden decrease can be a decrease or drop of more than a certain magnitude over a predetermined period of time. The magnitude of the decrease or drop can be 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, or any other magnitude greater than 50% or less than 100%, e.g., 80%, 85%, 90%, or 95%. The decrease or drop can be detected over a period of time. The period can be, for example, without limitation, a few seconds or minutes, or up to several days. For example, without limitation, a 20% decrease or drop over an hour can be considered a sudden drop, which can trigger an indication, notification, alarm, or alert. The magnitude of a decrease or drop that is considered to be an abrupt decrease or drop may be predetermined or pre-set by the user or a third party such as a medical professional.

[0206] The sensor control unit 102 may include an adhesive layer 105, referred to as an adhesive patch, used to adhere the sensor housing to a tissue surface, such as skin. Implanting a sensor may include attaching the adhesive patch to the skin to immobilize the sensor and prevent or inhibit unwanted movement of the sensor and / or corresponding sensor control unit 102. As embodied herein, the adhesive patch may be configured to prevent or inhibit reapplication or re-adhesion of the adhesive patch to the skin once removed after initial implantation. The adhesive patch may, for example, but not limited to, harden or otherwise become unusable once partially or completely removed from the skin. Removing part or all of the adhesive patch may displace the sensor, thereby eliminating any current, voltage, charge, energy, potential, potential difference, or any other signal output by the sensor. This may trigger an alarm or alert notifying the wearer or a third party that the sensor has been removed. Additionally, as embodied herein, visual inspection of the adhesive patch once removed can indicate adverse sensor conditions caused by improper placement or undesired removal of the sensor, rather than a failure of the sensor electronics or operation.

[0207] As embodied herein, the sensor control unit 102 can include a proximity sensor. For example, without limitation, the proximity sensor can include a reed switch or a magnetic field sensor, such as a Hall Effect sensor. By way of example and not limitation, as embodied herein, the sensor control unit 102 can include a switch or other sensing component of a proximity sensor, and the adhesive layer 105 can include a magnet or other sensing component, or vice versa. When the adhesive layer 105 is detached from the wearer's skin or when the sensor is detached from the adhesive layer 105, the inductive connection between the two components can be disrupted. The disruption of the inductive connection can trigger an indication, notification, alarm, or alert.

[0208] Additionally or alternatively, as embodied herein, electrical contacts or traces may be formed between one or more components of the sensor control unit 102 and / or the adhesive layer 105. Movement of the adhesive layer 105 and other portions of the sensor control unit 102 may cut or interrupt the electrical contacts or traces. For example, when the adhesive layer 105 is detached from the wearer's skin or when the sensor is detached from the adhesive layer 105, the electrical contacts or traces may be interrupted, thereby triggering an indication, notification, alarm, or alert.

[0209] Additionally, the sensor control device 102 can include a colored temperature strip. The colored temperature strip can be attached to any portion of the sensor control device 102, including its housing. When the temperature strip is heated to a certain threshold temperature, the temperature strip changes color. The temperature strip can include a thermosensitive liquid crystal that can change color to indicate temperature. For example, the temperature strip can change from blue to red, purple to orange, or green to yellow. Any other color combinations can be used. The color change of the temperature strip can indicate overheating of the analyte sensor, which can disable enzymes located on one or more active areas of the sensor or otherwise prevent the sensor from detecting one or more analyte levels, such as alcohol levels. The enzymes on one or more active areas can be disabled, while the enzymes on one or more other active areas can remain active. In some examples, the temperature strip can indicate that the sensor control device 102 has been heated to between 150°F (65.6°C) and 250°F (121°C).

[0210] The above exemplary embodiments can help ensure accuracy of analyte levels and determine adverse analyte sensor conditions, including failure of sensor components or electronics and / or unwanted or inadvertent displacement or removal of the sensor after initial implantation. These quality control mechanisms can trigger or provide notifications, alerts, or alarms to help the wearer and other interested professionals confirm proper functioning of the analyte sensor.

[0211] For purposes of example only and not limitation, the alcohol sensors described herein can be used for a variety of purposes, including, but not limited to, personal health monitoring, enforcement or monitoring of compliance with alcohol-related regulations or agreements, group therapy, and any other use for information regarding a person's or group's alcohol level, which may be indicative of a BAC as described herein. For example, but not limited to, alcohol sensors can be used for self-monitoring by a user or remote monitoring by a caregiver or healthcare provider to enable a user to accurately monitor their alcohol intake over a period of time, for example, but not limited to, to help a user identify unsafe amounts of alcohol intake and / or control alcohol intake to a desired level. As embodied herein, the alcohol sensor can be worn for a desired period of time, which may be any of the wearing periods described herein, and the results can be reported to the user for analysis and / or to the user's healthcare provider for review prior to a medical appointment.

[0212] As embodied herein, by way of example only, an alcohol sensor may be used to enforce compliance with alcohol-related conditions or restrictions of a criminal parole, probation, or diversion program for a person subject to alcohol-related conditions or restrictions. As embodied herein, a user's alcohol level may be transmitted to a parole, probation, or diversion officer or other monitoring entity responsible for enforcing compliance with the conditions of such programs. Additionally or alternatively, as embodied herein, an alcohol sensor may be used to enforce compliance with occupational or workplace rules or regulations regarding alcohol, for example, safety rules and regulations including the use of alcohol during or before operating a truck or other motor vehicle, machinery, or other heavy equipment, and may communicate an employee's alcohol level to an employer or other entity responsible for monitoring compliance with such rules or regulations. Additionally, as embodied herein, the alcohol sensor can be used to activate or disable external devices, such as automobiles, machinery, or other heavy equipment, which can be activated when the alcohol sensor is used to confirm that the user's alcohol level is low enough for safe operation by the user, and / or can be locked or disabled if the alcohol sensor indicates that the user's alcohol level is unsafe for operation of the external device.

[0213] Additionally, or as a further alternative, alcohol sensors can be used for group support for alcohol sobriety. Support group members may be a formal or informal group of people interested in achieving or maintaining sobriety from alcohol consumption, each wearing an alcohol sensor and agreeing to share alcohol sensor information with each other member of the support group, for example, via the cloud-based system and monitoring application described herein. Alcohol sensor information can include the user's alcohol level and whether the alcohol sensor is active or operational. Sharing alcohol sensor information with the support group can encourage users to continue abstinence through peer support and can notify the support group when encouragement or intervention with members should be provided.

[0214] According to other aspects of the disclosed subject matter, an alcohol sensor can be used to provide a user with personalized insights based on alcohol level data. By way of example and not limitation, as embodied herein, alcohol level data can be correlated with the user's amount of dehydration caused by alcohol consumption. The alcohol level data can be used, for example, to determine the user's BAC over time, as described. As embodied herein, the user's BAC over time can be correlated with the user's amount of dehydration, for example, by the data receiving device 120 or the multipurpose data receiving device 130. The data receiving device 120 or the multipurpose data receiving device 130 can be configured to provide advice based on the user's amount of dehydration determined from the alcohol level data. By way of example and not limitation, the data receiving device 120 or the multipurpose data receiving device 130 can be configured to recommend to the user that they take a specific amount of oral electrolyte solution (e.g., Pedialyte® by Abbott Laboratories) based on the determined amount of dehydration. Such insights can be provided in combination with other data, including data from other analyte sensors. For example, but not by way of limitation, as embodied herein, a dual alcohol-ketone sensor can provide additional insight related to alcohol intake. For example, a ketogenic diet can cause a person's BAC to increase more quickly, and thus a data receiving device 120 or a multipurpose data receiving device 130 in communication with a dual alcohol-ketone sensor (or separate alcohol and ketone sensors) can provide an indication to a user when the user's ketone analyte level or ketosis level is at risk of or is increasing the user's BAC more quickly than when not in ketosis or with lower ketone levels.

[0215] While the disclosed subject matter has been described herein with reference to certain preferred embodiments for purposes of illustration and not limitation, those skilled in the art will recognize that various modifications and improvements can be made to the disclosed subject matter without departing from its scope. Moreover, while individual features of one embodiment of the disclosed subject matter may be described herein or shown in drawings of one embodiment but not other embodiments, it will be readily apparent that individual features of one embodiment may be combined with one or more features of another embodiment or features from multiple embodiments.

[0216] In addition to the specific embodiments claimed below, the disclosed subject matter is also directed to other embodiments having any other possible combinations of the dependent features claimed below and disclosed above. Thus, the specific features recited in the dependent claims and disclosed above can be combined with each other in other possible combinations. Thus, the foregoing descriptions of specific embodiments of the disclosed subject matter are presented for purposes of illustration and description and are not intended to be exhaustive or to limit the disclosed subject matter to the disclosed embodiments.

[0217] It will be apparent to those skilled in the art that various modifications and variations can be made in the methods and systems of the disclosed subject matter without departing from the spirit or scope of the disclosed subject matter. Thus, it is intended that the disclosed subject matter cover modifications and variations that come within the scope of the appended claims and their equivalents.

Claims

1. an in-vivo alcohol sensor, the in-vivo alcohol sensor being positioned so that at least a portion of the sensor is in contact with a bodily fluid; a reader comprising one or more processors, The reader: receiving a signal from the in-vivo alcohol sensor; determining a blood alcohol concentration based in part on the signal received from the in-vivo alcohol sensor; Detecting an adverse condition of the in-vivo alcohol sensor, including a failure or misalignment of the in-vivo alcohol sensor, based on a variation in a background signal amplitude of the in-vivo alcohol sensor exceeding a background signal variation threshold, wherein the background signal variation threshold during an initial wearing period of the in-vivo alcohol sensor is different from the background signal variation threshold during a remaining wearing period of the in-vivo alcohol sensor; The system is configured to output an instruction based on the detected adverse situation.

2. The system of claim 1 , wherein the in-vivo alcohol sensor is used to detect ethanol levels.

3. the in-vivo alcohol sensor comprises a temperature sensor, and the one or more processors: The system of claim 1 or 2, configured to determine the adverse situation when the detected temperature falls below a threshold body temperature after a certain wearing period.

4. The system further comprises a glucose sensor, and wherein the one or more processors: The system of claim 1 , configured to determine the adverse situation based on at least one of a glucose level or an ethanol level.

5. The one or more processors:

5. The system of claim 1, configured to determine the adverse situation when the signal amplitude of the in-vivo alcohol sensor is below a background signal amplitude.

6. The one or more processors:

6. The system of claim 1, configured to detect when a variation in the background signal amplitude of the in-vivo alcohol sensor over a period of time exceeds a background signal variation threshold.

7. the one or more processors:

7. The system of claim 1, configured to detect a sudden drop in the signal amplitude of the in-vivo alcohol sensor.

8. 8. The system of claim 1, wherein the in-vivo alcohol sensor is attached to an adhesive patch configured to be applied to the skin, the adhesive patch configured to be disabled when removed from the skin.

9. The in-vivo alcohol sensor is attached to an adhesive patch configured to be applied to the skin, the in-vivo alcohol sensor comprises a proximity sensor, and the one or more processors:

9. The system of claim 1, wherein the in-vivo alcohol sensor is configured to detect removal from the adhesive patch.

10. The system of claim 9 , wherein the proximity sensor is a reed switch or a magnetic sensor.

11. 11. The system of claim 1, wherein a temperature strip is secured to the in-vivo alcohol sensor, the temperature strip including a visual indicator with a color indicating a change in temperature above a temperature threshold.

12. the one or more processors:

12. The system of claim 1, further configured to display blood alcohol content on the reader.

13. 13. The system of any one of claims 1 to 12, wherein the indication is visual, audible or vibratory.

14. the one or more processors:

14. The system of claim 1, further configured to activate or deactivate an external device based on the determined blood alcohol concentration.

15. receiving a signal from an in-vivo alcohol sensor, the in-vivo alcohol sensor being positioned such that at least a portion of the in-vivo alcohol sensor is in contact with a bodily fluid; determining a blood alcohol concentration based in part on the signal received from the in-vivo alcohol sensor; Detecting an adverse condition of the in-vivo alcohol sensor; and outputting an indication based on the detected adverse situation, The method, wherein the adverse situation includes a failure or misalignment of the in-vivo alcohol sensor, and the adverse situation is detected based on a fluctuation in the background signal amplitude of the in-vivo alcohol sensor exceeding a background signal fluctuation threshold, wherein the background signal fluctuation threshold during an initial wearing period of the in-vivo alcohol sensor is different from the background signal fluctuation threshold for the remainder of the wearing period of the in-vivo alcohol sensor.

16. 16. The method of claim 15, wherein the in-vivo alcohol sensor is used to detect ethanol levels.

17. 17. The method of claim 15 or 16, further comprising determining the adverse event when the detected temperature falls below a threshold body temperature after a specified period of wear.

18. 18. The method of any one of claims 15 to 17, further comprising determining the adverse situation based on at least one of a glucose level or an ethanol level.

19. 19. The method of any one of claims 15 to 18, further comprising determining the adverse situation when the signal amplitude of the in-vivo alcohol sensor is below a background signal amplitude.

20. 20. The method of any one of claims 15 to 19, further comprising detecting when a variation in the background signal amplitude of the in-vivo alcohol sensor over a period of time exceeds a background signal variation threshold.

21. 21. The method of any one of claims 15 to 20, further comprising detecting a sudden drop in the signal amplitude of the in-vivo alcohol sensor.

22. 22. The method of any one of claims 15 to 21, further comprising hardening an adhesive patch attached to the in-vivo alcohol sensor upon removal from the skin.

23. 23. The method of any one of claims 15 to 22, wherein the in-vivo alcohol sensor is attached to an adhesive patch configured to be applied to the skin, and the method further comprises detecting, using a proximity sensor, that the in-vivo alcohol sensor is removed from the adhesive patch.

24. 24. The method of claim 23, wherein the proximity sensor is a reed switch or a magnetic sensor.

25. 25. The method of any one of claims 15 to 24, further comprising changing a visual indication of a temperature strip affixed to the in-vivo alcohol sensor, the visual indication including a color indicating a change in temperature above a temperature threshold.

26. 26. The method of any one of claims 15 to 25, further comprising displaying the blood alcohol content on a reader.

27. 27. The method of any one of claims 15 to 26, wherein the outputted indication is visual, audible or vibratory.

28. 28. The method of any one of claims 15 to 27, further comprising activating or disabling an external device based on the determined blood alcohol concentration.

29. The system of claim 1 , wherein the initial wear period ranges from 2 to 7 days.

30. 16. The method of claim 15, wherein the initial wear period ranges from 2 to 7 days.

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