[go: up one dir, main page]

WO2025090556A1 - Systèmes et procédés d'estimation d'épaisseur de membrane par mesure électrochimique - Google Patents

Systèmes et procédés d'estimation d'épaisseur de membrane par mesure électrochimique Download PDF

Info

Publication number
WO2025090556A1
WO2025090556A1 PCT/US2024/052484 US2024052484W WO2025090556A1 WO 2025090556 A1 WO2025090556 A1 WO 2025090556A1 US 2024052484 W US2024052484 W US 2024052484W WO 2025090556 A1 WO2025090556 A1 WO 2025090556A1
Authority
WO
WIPO (PCT)
Prior art keywords
membrane
sensor
period
time
analyte
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
PCT/US2024/052484
Other languages
English (en)
Inventor
Albert Gutes-Regidor
Mark S. Yahnke
Udo Hoss
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Abbott Diabetes Care Inc
Original Assignee
Abbott Diabetes Care Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Abbott Diabetes Care Inc filed Critical Abbott Diabetes Care Inc
Publication of WO2025090556A1 publication Critical patent/WO2025090556A1/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue
    • A61B5/14532—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue for measuring glucose, e.g. by tissue impedance measurement
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue
    • A61B5/14546—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue for measuring analytes not otherwise provided for, e.g. ions, cytochromes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue
    • A61B5/1468—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue using chemical or electrochemical methods, e.g. by polarographic means
    • A61B5/1486—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue using chemical or electrochemical methods, e.g. by polarographic means using enzyme electrodes, e.g. with immobilised oxidase
    • A61B5/14865—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue using chemical or electrochemical methods, e.g. by polarographic means using enzyme electrodes, e.g. with immobilised oxidase invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue
    • A61B5/1495—Calibrating or testing of in-vivo probes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B2560/00—Constructional details of operational features of apparatus; Accessories for medical measuring apparatus
    • A61B2560/02—Operational features
    • A61B2560/0266—Operational features for monitoring or limiting apparatus function

Definitions

  • the disclosure generally relates to measurement systems, and more specifically to systems and methods for estimating membrane thickness by electrochemical measurements.
  • Continuous analyte monitoring systems typically provide a comprehensive picture of monitored analyte levels of a subject.
  • CGM continuous glucose monitoring
  • Commercially available CGM systems typically use a percutaneously or transcutaneously placed glucose sensor over a time period spanning several days to approximately a week or more, during which time period the real time glucose information is monitored and provided to the patient to take any necessary corrective actions for purposes of controlling potential glycemic excursions.
  • Typical glucose sensors are manufactured in batches or lots and after each use (for the intended three, five, seven days or some other prescribed time period), are discarded and replaced with a new sensor.
  • Exemplary CGM systems are described in PCT Publication No. W02010099507A1 and U.S. Publication No. 2019/0254575A1, the contents of each of which are incorporated by reference in their entirety.
  • Such CGM systems include a sensor working electrode with a membrane having substantially uniform membrane thickness disposed over the working electrode.
  • the area of the sensor working electrode and/or the membrane thickness is controlled, e.g., to control the sensor sensitivity across manufactured lots or batches.
  • the sensor sensitivity to glucose is inversely proportional to the thickness of the membrane and the sensitivity is proportional to the area of the active region of the working electrode.
  • these sensors are manufactured such that the sensors do not require calibration by the user or by the CGM system.
  • the disclosed subject matter is directed to systems and methods for estimating membrane thickness by electrochemical measurements.
  • a method for estimating membrane thickness by electrochemical measurements includes providing a sensor having a working electrode and coating a tip of the sensor with a membrane coating such that the membrane coating is disposed over the working electrode.
  • the method also includes embedding analyte into a capping membrane and disposing the capping membrane over at least a portion of the tip of the sensor.
  • the method further includes detecting, by a working electrode, a plurality of signals over a period of time, determining current measurements from the plurality of signals, and estimating a thickness of the membrane coating at least in part by analyzing a relationship of the current measurements to the period of time.
  • a system includes a sensor, a membrane coating, a capping membrane, a working electrode, and a processor.
  • the sensor comprises the working electrode.
  • the membrane coating is disposed over a tip of the sensor such that the membrane coating is disposed over the working electrode.
  • the capping membrane is embedded with analyte and is disposed over at least a portion of the tip of the sensor.
  • the working electrode is operable to detect a plurality of signals over a period of time.
  • the processor is operable to determine current measurements from the plurality of signals and estimate a thickness of the membrane coating at least in part by analyzing a relationship of the current measurements to the period of time.
  • a sensor includes a tip, a membrane coating, a capping membrane, a working electrode, and a processor.
  • the membrane coating is disposed over a tip of the sensor such that the membrane coating is disposed over the working electrode.
  • the capping membrane is embedded with analyte and is disposed over at least a portion of the tip of the sensor.
  • the working electrode is configured to detect a plurality of signals over a period of time.
  • the processor is configured to determine current measurements from the plurality of signals and estimate a thickness of the membrane coating at least in part by analyzing a relationship of the current measurements to the period of time.
  • the membrane coating can include an analyte limiting barrier.
  • the analyte limiting barrier can include a glucose limiting barrier.
  • the analyte can be glucose, ketone, or lactate.
  • the membrane coating can include an interference domain.
  • the capping membrane can include a Poly(4-Vinylpyridine) (P4VP)-co- Polystyrene Sulfonate (PSS) (P4VP-CO-PSS) membrane.
  • the capping membrane can include a polyurethane membrane.
  • Disposing the capping membrane over at least a portion of the tip of the sensor can include disposing the capping membrane over the membrane coating.
  • FIG. 1 illustrates a system overview of a sensor applicator, reader device, monitoring system, network, and remote system.
  • FIG. 2A illustrates a block diagram depicting a reader device.
  • FIGS. 2B and 2C illustrate block diagrams of sensor control devices.
  • FIG. 3 A illustrates a proximal perspective view depicting a user preparing a tray for an assembly.
  • FIG. 3B illustrates a side view depicting a user preparing an applicator device for an assembly.
  • FIG. 3C illustrates a proximal perspective view depicting a user inserting an applicator device into a tray during an assembly.
  • FIG. 3D illustrates a proximal perspective view depicting a user removing an applicator device from a tray during an assembly.
  • FIG. 3E illustrates a proximal perspective view depicting a patient applying a sensor using an applicator device.
  • FIG. 3F illustrates a proximal perspective view depicting a patient with an applied sensor and a used applicator device.
  • FIG. 4A illustrates a side view depicting an applicator device coupled with a cap.
  • FIG. 4B illustrates a side perspective view depicting an applicator device and cap decoupled.
  • FIG. 4C illustrates a perspective view depicting a distal end of an applicator device and electronics housing.
  • FIG. 4D illustrates a top perspective view of an exemplary applicator device in accordance with the disclosed subject matter.
  • FIG. 4E illustrates a bottom perspective view of the applicator device of FIG. 4D.
  • FIG. 4F illustrates an exploded view of the applicator device of FIG. 4D.
  • FIG. 4G illustrates a side cutaway view of the applicator device of FIG. 4D.
  • FIG. 5 illustrates a proximal perspective view depicting a tray with sterilization lid coupled.
  • FIG. 6A illustrates a proximal perspective cutaway view depicting a tray with sensor delivery components.
  • FIG. 6B illustrates a proximal perspective view depicting sensor delivery components.
  • FIGS. 7A-7C illustrate cross-sectional diagrams of analyte sensors including a single active area.
  • FIGS. 8A-8C illustrate cross-sectional diagrams of analyte sensors including two active areas.
  • FIG. 9 illustrates a cross-sectional diagram of an analyte sensor including two active areas.
  • FIGS. 10 A- IOC show perspective views of analyte sensors including two active areas upon separate working electrodes.
  • FIG. 11 illustrates a graph depicting the in vitro sensitivity of an amperometric analyte sensor.
  • FIGS. 13A and 13B illustrate the process of manufacturing a sensor tip for a sensor of the system described in FIG. 12, in accordance with the disclosed subject matter.
  • FIG. 14 illustrates a graph of an amperometric response of the sensor described in FIG.
  • FIG. 15 illustrates a graph of the obtained charge due to glucose diffusion related to the sensor described in FIG. 12, in accordance with the disclosed subject matter.
  • FIG. 16 illustrates a computer system that can be used by the systems and methods described herein, in accordance with the disclosed subject matter.
  • FIG. 17 illustrates a method for estimating membrane thickness by electrochemical measurements, in accordance with the disclosed subject matter.
  • FIG. 18 illustrates a cross-sectional diagram of an analyte sensor, in accordance with the disclosed subject matter.
  • FIG. 19 illustrates an exemplary cross-sectional diagram of the analyte sensor of FIG.
  • FIG. 20 illustrates an exemplary cross-sectional diagram of the analyte sensor of FIG.
  • the present embodiments are useful in connection with a device that is used to measure or monitor an analyte (e.g., glucose), such as any such device described herein.
  • analyte e.g., glucose
  • the embodiments described herein can be used to monitor and/or process information regarding any number of one or more different analytes.
  • Analytes that may be monitored include, but are not limited to, acetyl choline, amylase, bilirubin, carbon dioxide, cholesterol, chorionic gonadotropin, glycosylated hemoglobin (HbAlc), creatine kinase (e.g., CK-MB), creatine, creatinine, DNA, fructosamine, glucose, glucose derivatives, glutamine, growth hormones, hormones, ketones, ketone bodies, lactate, oxygen, peroxide, prostatespecific antigen, proteins, prothrombin, RNA, thyroid stimulating hormone, troponin, and any combination thereof.
  • HbAlc glycosylated hemoglobin
  • CK-MB creatine kinase
  • the concentration of drugs may be monitored in addition to or instead of analytes.
  • antibiotics e.g., gentamicin, vancomycin, and the like
  • digitoxin digoxin
  • digoxin digoxin
  • drugs of abuse theophylline
  • warfarin may be monitored in addition to or instead of analytes.
  • the analytes may be monitored at the same or different times.
  • a device that is used to measure or monitor another analyte (e.g., ketones, ketone bodies, HbAlc, and the like), including oxygen, carbon dioxide, proteins, drugs, or another moiety of interest, for example, or any combination thereof, found in bodily fluid, including subcutaneous fluid, dermal fluid, interstitial fluid, or other bodily fluid of interest, for example, or any combination thereof.
  • another analyte e.g., ketones, ketone bodies, HbAlc, and the like
  • oxygen, carbon dioxide, proteins, drugs, or another moiety of interest for example, or any combination thereof
  • bodily fluid including subcutaneous fluid, dermal fluid, interstitial fluid, or other bodily fluid of interest, for example, or any combination thereof.
  • the device is in good contact, such as thorough and substantially continuous contact, with the bodily fluid.
  • membrane thickness measurements are typically carried out by optical microscope measurements. For instance, a thickness dimension of a flexible substrate covered by the membrane is subtracted to calculate an approximate membrane thickness.
  • flexible substrate thickness is not often measured for each unit and may vary from lot to lot.
  • membrane thickness is humidity dependent, and while a production team may measure membrane thickness at a low relative humidity (RH) (e.g., ten percent (10%)), the humidity can vary elsewhere.
  • RH relative humidity
  • ambient RH e.g., fifty percent (50%)
  • membrane thickness is typically assumed to be equal on both sides of the substrate, there are data suggesting this is not always the case for each unit.
  • the subject matter of this disclosure describe systems and methods for estimating membrane thickness by electrochemical measurements.
  • a method for estimating membrane thickness by electrochemical measurements includes providing a sensor having a working electrode and coating a tip of the sensor with a membrane coating such that the membrane coating is disposed over the working electrode.
  • the method also includes embedding analyte into a capping membrane and disposing the capping membrane over at least a portion of the tip of the sensor.
  • the method further includes detecting, by a working electrode of the sensor, a plurality of signals over a period of time, determining current measurements from the plurality of signals, and estimating a thickness of the membrane coating at least in part by analyzing a relationship of the current measurements to the period of time.
  • a system includes a sensor, a membrane coating, a capping membrane, a working electrode, and a processor.
  • the sensor includes the working electrode.
  • the membrane coating is disposed over a tip of the sensor such that the membrane coating is disposed over the working electrode.
  • the capping membrane is embedded with analyte and is disposed over at least a portion of the tip of the sensor.
  • the working electrode is operable to detect a plurality of signals over a period of time.
  • the processor is operable to determine current measurements from the plurality of signals and estimate a thickness of the membrane coating at least in part by analyzing a relationship of the current measurements to the period of time.
  • a sensor in accordance with the disclosed subject matter, includes a tip, a membrane coating, a capping membrane, a working electrode, and a processor.
  • the membrane coating is disposed over a tip of the sensor such that the membrane coating is disposed over the working electrode.
  • the capping membrane is embedded with analyte and is disposed over at least a portion of the tip of the sensor.
  • the working electrode is configured to detect a plurality of signals over a period of time.
  • the processor is configured to determine current measurements from the plurality of signals and estimate a thickness of the membrane coating at least in part by analyzing a relationship of the current measurements to the period of time.
  • the membrane coating includes an analyte limiting barrier.
  • the analyte limiting barrier can include a glucose limiting barrier.
  • the analyte includes glucose, ketone, or lactate.
  • the membrane coating includes an interference domain.
  • a permeability measurement of the capping membrane can be higher than a permeability measurement of the membrane coating.
  • the capping membrane can include a P4VP-co-PSS membrane. Disposing the capping membrane over at least a portion of the tip of the sensor can include disposing the capping membrane over the membrane coating.
  • Certain systems and methods described herein analyze the electrochemical measurements generated from a glucose sensor to provide information about membrane thickness in-vivo during the initial wear (e.g., first five to ten (5-10) minutes) of the sensor.
  • the electrochemical measurements may be used to check for correct function of the sensor. For example, the sensor current after insertion in the body should show a local maximum shortly after the initial current decay. If that local maximum is not present, the sensor may not be inserted correctly or may not function properly. Algorithms may then trigger a warning and ask for removing and/or replacing of the sensor.
  • FIG. 1 is a conceptual diagram depicting an analyte monitoring system 100 that includes a sensor applicator device 150, a sensor control device 102, and a reader device 120, in accordance with the disclosed subject matter.
  • sensor applicator device 150 can be used to deliver sensor control device 102 to a monitoring location on a user’s skin where a sensor 104 is maintained in position for a period of time by an adhesive patch 105.
  • Sensor control device 102 is further described in FIGS. 2B and 2C and can communicate with reader device 120 via a communication path 140 using a wired or wireless technique.
  • Example wireless protocols include Bluetooth, Bluetooth Low Energy (BLE, BTLE, Bluetooth SMART, etc.), Near Field Communication (NFC) and others.
  • Reader device 120 can communicate with local computer system 170 via a communication path 141 using a wired or wireless technique.
  • 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.
  • Wireless communication can include any of a number of applicable wireless networking protocols including Bluetooth, Bluetooth Low Energy (BTLE), Wi-Fi or others.
  • Local computer system 170 can communicate via communications path 143 with a network 190 similar to how reader device 120 can communicate via a communications path 142 with network 190, by wired or wireless technique as described previously.
  • Network 190 can be any of a number of networks, such as private networks and public networks, local area or wide area networks, and so forth.
  • a trusted computer system 180 can include a server and can provide authentication services and secured data storage and can communicate via communications path 144 with network 190 by wired or wireless technique.
  • FIG. 2A is a block diagram depicting a reader device configured as a smartphone.
  • reader device 120 can include a display 122, input component 121, and a processing core 206 including a communications processor 222 coupled with memory 223 and an applications processor 224 coupled with memory 225.
  • a processing core 206 including a communications processor 222 coupled with memory 223 and an applications processor 224 coupled with memory 225.
  • separate memory 230 can be separate memory 230, RF transceiver 228 with antenna 229, and power supply 226 with power management module 238.
  • a multi-functional transceiver 232 which can communicate over WiFi, NFC, Bluetooth, BTLE, and GPS with an antenna 234. As understood by one of skill in the art, these components are electrically and communicatively coupled in a manner to make a functional device.
  • FIGS. 2B and 2C are block diagrams depicting sensor control device 102 having analyte sensor 104 and sensor electronics 160 (including analyte monitoring circuitry) that can have the majority of the processing capability for rendering end-result data suitable for display to the user, in accordance with the disclosed subject matter.
  • a single semiconductor chip 161 is depicted that can be a custom application specific integrated circuit (ASIC). Shown within ASIC 161 are certain high-level functional units, including an analog front end (AFE) 162, power management (or control) circuitry 164, processor 166, and communication circuitry 168 (which can be implemented as a transmitter, receiver, transceiver, passive circuit, or otherwise according to the communication protocol).
  • AFE analog front end
  • AFE power management
  • processor 166 processor 166
  • communication circuitry 168 which can be implemented as a transmitter, receiver, transceiver, passive circuit, or otherwise according to the communication protocol.
  • both AFE 162 and processor 166 are used as analyte monitoring circuitry, but either circuit can perform the analyte monitoring function.
  • Processor 166 can include one or more processors, microprocessors, controllers, and/or microcontrollers, each of which can be a discrete chip or distributed amongst (and a portion of) a number of different chips.
  • a memory 163 is also included within ASIC 161 and can be shared by the various functional units present within ASIC 161 or can be distributed amongst two or more of them. Memory 163 can also be a separate chip. Memory 163 can be volatile and/or non-volatile memory.
  • ASIC 161 is coupled with power source 176, which can be a coin cell battery, or the like.
  • AFE 162 interfaces with in vivo analyte sensor 104 and receives measurement data therefrom and outputs the data to processor 166 in digital form, which in turn processes the data to arrive at the end-result glucose discrete and trend values, etc. This data can then be provided to communication circuitry 168 for sending, by way of antenna 171, to reader device 120 (not shown), for example, where minimal further processing is needed by the resident software application to display the data.
  • FIG. 2C is similar to FIG. 2B but instead includes two discrete semiconductor chips 161 and 174, which can be packaged together or separately.
  • AFE 162 is resident on ASIC 161.
  • Processor 166 is integrated with power management circuitry 164 and communication circuitry 168 on chip 174.
  • AFE 162 includes memory 163 and chip 174 includes memory 165, which can be isolated or distributed within.
  • AFE 162 is combined with power management circuitry 164 and processor 166 on one chip, while communication circuitry 168 is on a separate chip.
  • both AFE 162 and communication circuitry 168 are on one chip, and processor 166 and power management circuitry 164 are on another chip. It should be noted that other chip combinations are possible, including three or more chips, each bearing responsibility for the separate functions described, or sharing one or more functions for fail-safe redundancy. Exemplary Assembly Processes for Sensor Control Devices
  • FIGS. 3A-3D depict an assembly process for sensor control device 102 by a user, including preparation of separate components before coupling the components in order to ready the sensor for delivery, in accordance with the disclosed subject matter.
  • FIG. 3 A is a proximal perspective view depicting a user preparing a container 810, configured here as a tray (although other packages can be used), for an assembly process, in accordance with the disclosed subject matter.
  • the user can accomplish this preparation by removing lid 812 from tray 810 to expose platform 808, for instance by peeling a non-adhered portion of lid 812 away from tray 810 such that adhered portions of lid 812 are removed. Removal of lid 812 can be appropriate in various embodiments so long as platform 808 is adequately exposed within tray 810. Lid 812 can then be placed aside.
  • FIG. 3B is a side view depicting a user preparing an applicator device 150 for assembly, in accordance with the disclosed subject matter.
  • Applicator device 150 can be provided in a sterile package sealed by a cap 708. Preparation of applicator device 150 can include uncoupling housing 702 from cap 708 to expose sheath 704 (FIG. 3C). This can be accomplished by unscrewing (or otherwise uncoupling) cap 708 from housing 702. Cap 708 can then be placed aside.
  • FIG. 3C is a proximal perspective view depicting a user inserting an applicator device 150 into a tray 810 during an assembly, in accordance with the disclosed subject matter.
  • the user can insert sheath 704 into platform 808 inside tray 810 after aligning housing orienting feature 816 (or slot or recess) and tray orienting feature 924 (an abutment or detent). Inserting sheath 704 into platform 808 temporarily unlocks sheath 704 relative to housing 702 and also temporarily unlocks platform 808 relative to tray 810.
  • removal of applicator device 150 from tray 810 will result in the same state prior to initial insertion of applicator device 150 into tray 810 (i.e., the process can be reversed or aborted at this point and then repeated without consequence).
  • Sheath 704 can maintain position within platform 808 with respect to housing 702 while housing 702 is distally advanced, coupling with platform 808 to distally advance platform 808 with respect to tray 810. This step unlocks and collapses platform 808 within tray 810. Sheath 704 can contact and disengage locking features (not shown) within tray 810 that unlock sheath 704 with respect to housing 702 and prevent sheath 704 from moving (relatively) while housing 702 continues to distally advance platform 808. At the end of advancement of housing 702 and platform 808, sheath 704 is permanently unlocked relative to housing 702. A sharp and sensor (not shown) within tray 810 can be coupled with an electronics housing (not shown) within housing 702 at the end of the distal advancement of housing 702. Operation and interaction of the applicator device 150 and tray 810 are further described below.
  • FIG. 3D is a proximal perspective view depicting a user removing an applicator device 150 from a tray 810 during an assembly in accordance with the disclosed subject matter.
  • a user can remove applicator device 150 from tray 810 by proximally advancing housing 702 with respect to tray 810 or other motions having the same end effect of uncoupling applicator device 150 and tray 810.
  • the applicator device 150 is removed with sensor control device 102 (not shown) fully assembled (sharp, sensor, electronics) therein and positioned for delivery.
  • FIG. 3E is a proximal perspective view depicting a patient applying sensor control device 102 using applicator device 150 to a target area of skin, for instance, on an abdomen or other appropriate location in accordance with the disclosed subject matter.
  • Advancing housing 702 distally collapses sheath 704 within housing 702 and applies the sensor to the target location such that an adhesive layer on the bottom side of sensor control device 102 adheres to the skin.
  • the sharp is automatically retracted when housing 702 is fully advanced, while the sensor (not shown) is left in position to measure analyte levels.
  • FIG. 3F is a proximal perspective view depicting a patient with sensor control device 102 in an applied position in accordance with the disclosed subject matter. The user can then remove applicator device 150 from the application site.
  • System 100 can provide a reduced or eliminated chance of accidental breakage, permanent deformation, or incorrect assembly of applicator components compared to prior art systems. Since applicator housing 702 directly engages platform 808 while sheath 704 unlocks, rather than indirect engagement via sheath 704, relative angularity between sheath 704 and housing 702 will not result in breakage or permanent deformation of the arms or other components. The potential for relatively high forces (such as in conventional devices) during assembly will be reduced, which in turn reduces the chance of unsuccessful user assembly.
  • FIG. 4A is a side view depicting an applicator device 150 coupled with screw cap 708, in accordance with the disclosed subject matter. This is an example of how applicator device 150 can be shipped to and received by a user, prior to assembly by the user with a sensor.
  • FIG. 4B is a side perspective view depicting applicator device 150 and cap 708 after being decoupled.
  • FIG. 4C is a perspective view depicting a distal end of an applicator device 150 with electronics housing 706 and adhesive patch 105 removed from the position they would have retained within sensor carrier 710 of sheath 704, when cap 708 is in place, in accordance with the disclosed subject matter.
  • the applicator device 20150 can be provided to a user as a single integrated assembly.
  • FIGS. 4D and 4E provide perspective top and bottom views, respectively, of the applicator device 20150
  • FIG. 4F provides an exploded view of the applicator device 20150
  • FIG. 4G provides a side cutaway view.
  • the perspective views illustrate how applicator device 20150 is shipped to and received by a user.
  • the exploded and cut-away views illustrate the components of the applicator device 20150.
  • the applicator device 20150 can include a housing 20702, gasket 20701, sheath 20704, sharp carrier 201102, spring 205612, sensor carrier 20710 (also referred to as a “puck carrier”), sharp hub 205014, sensor control device (also referred to as a “puck”) 20102, adhesive patch 20105, desiccant 20502, cap 20708, serial label 20709, and tamper evidence feature 20712. As received by a user, only the housing 20702, cap 20708, tamper evidence feature 20712, and label 20709 are visible.
  • the tamper evidence feature 20712 can be, for example, a sticker coupled to each of the housing 20702 and the cap 20708, and tamper evidence feature 20712 can be damaged, for example, irreparably, by uncoupling housing 20702 and cap 20708, thereby indicating to a user that the housing 20702 and cap 20708 have been previously uncoupled.
  • FIG. 5 is a proximal perspective view depicting a tray 810 with sterilization lid 812 removably coupled thereto, which may be representative of how the package is shipped to and received by a user prior to assembly.
  • FIG. 6A is a proximal perspective cutaway view depicting sensor delivery components within tray 810 in accordance with the disclosed subject matter.
  • Platform 808 is slidably coupled within tray 810.
  • Desiccant 502 is stationary with respect to tray 810.
  • Sensor module 504 is mounted within tray 810.
  • FIG. 6B is a proximal perspective view depicting sensor module 504 in greater detail in accordance with the disclosed subject matter.
  • retention arm extensions 1834 of platform 808 releasably secure sensor module 504 in position.
  • Module 2200 is coupled with connector 2300, sharp module 2500 and sensor (not shown) such that during assembly they can be removed together as sensor module 504. Additional features of the system are contemplated herein such as disclosed in U.S. Application No. 18/220,468, the contents of which is incorporated herein by reference it its entirety.
  • Sensor configurations featuring a single active area that is configured for detection of a corresponding single analyte can employ two-electrode or three-electrode detection motifs, as described further herein in reference to FIGS. 7A-7C.
  • Sensor configurations featuring two different active areas for detection of the same or separate analytes, either upon separate working electrodes or upon the same working electrode, are described separately thereafter in reference to FIGS. 8A-8C.
  • Sensor configurations having multiple working electrodes can be particularly advantageous for incorporating two different active areas within the same sensor tail, since the signal contribution from each active area can be determined more readily.
  • three-electrode sensor configurations can include a working electrode, a counter electrode and a reference electrode.
  • Related two-electrode sensor configurations can include a working electrode and a second electrode, in which the second electrode can function as both a counter electrode and a reference electrode (z.e., a counter/reference electrode).
  • the various electrodes can be at least partially stacked (layered) upon one another and/or laterally spaced apart from one another upon the sensor tail.
  • Suitable sensor configurations can be substantially flat in shape, substantially cylindrical in shape or any suitable shape.
  • the various electrodes can be electrically isolated from one another by a dielectric material or similar insulator.
  • Analyte sensors featuring multiple working electrodes can similarly include at least one additional electrode.
  • the one additional electrode can function as a counter/reference electrode for each of the multiple working electrodes.
  • one of the additional electrodes can function as a counter electrode for each of the multiple working electrodes and the other of the additional electrodes can function as a reference electrode for each of the multiple working electrodes.
  • FIG. 7A shows a diagram of an illustrative two-electrode analyte sensor configuration, which is compatible for use in the disclosure herein. As shown, analyte sensor 700a includes substrate 712 disposed between working electrode 714 and counter/reference electrode 716.
  • working electrode 714 and counter/reference electrode 716 can be located upon the same side of substrate 712 with a dielectric material interposed in between (configuration not shown).
  • Active area 718 is disposed as at least one layer upon at least a portion of working electrode 714.
  • Active area 718 can include multiple spots or a single spot configured for detection of an analyte at a low working electrode potential, as discussed further herein.
  • active area 718 can comprise an electron transfer agent described herein.
  • membrane 720 overcoats at least active area 718.
  • membrane 720 comprises a copolymer of the present disclosure.
  • membrane 720 can include a polyvinylpyridine (e.g., poly(2-vinylpyridine) or poly(4-vinylpyridine)), a polyvinylimidazole, a polyvinylpyridine copolymer (e.g., a copolymer of vinylpyridine and styrene), a polyvinylpyrrolidone, a polyamide, a polylactone, a polyimide, a polylactam, a functionalized polyamide, a functionalized polylactone, a functionalized polyimide, a functionalized polylactam, a polyacrylate, a poly siloxane (e.g., a poly carbosiloxane), a polyurethane, a polyether urethane
  • membrane 720 comprises a copolymer comprising a first monomer, e.g., an acrylamide (e.g., an N-alkyl acrylamide), and a second monomer comprising a heterocycle-containing component, e.g., a vinylpyridine, e.g., 4-vinylpyridine.
  • membrane 720 comprises a copolymer comprising a first monomer, e.g., a styrene, and a second monomer comprising a heterocyclecontaining component, e.g., a vinylpyridine, e.g., 4-vinylpyridine.
  • membrane 720 can include a polyvinylpyridine-co-styrene copolymer.
  • a polyvinylpyridine-co-styrene copolymer can include a polyvinylpyridine-co-styrene copolymer in which a portion of the pyridine nitrogen atoms are functionalized with a non-crosslinked polyethylene glycol tail and a portion of the pyridine nitrogen atoms were functionalized with an alkylsulfonic acid group, e.g., a propylsulfonic acid.
  • a derivatized polyvinylpyridine-co-styrene copolymer for use as a membrane polymer can be the 10Q5 polymer as described in U.S. Patent No. 8,761,857, the content of which is incorporated by reference herein in its entirety.
  • membrane 720 can include hydrophobic and hydrophilic regions.
  • a hydrophobic polymer of a membrane disclosed herein can be a polyurethane or polyether urethane urea.
  • Polyurethane is a polymer produced by the condensation reaction of a diisocyanate and a difunctional hydroxyl-containing material.
  • a polyurea is a polymer produced by the condensation reaction of a diisocyanate and a difunctional amine-containing material.
  • diisocyanates include aliphatic diisocyanates containing from about 3 to about 9 methylene unit and diisocyanates containing cycloaliphatic moieties.
  • membrane 720 can also overcoat some or all of working electrode 714 and/or counter/reference electrode 716, or the entirety of analyte sensor 700a.
  • One or both faces of analyte sensor 700a can be overcoated with membrane 720.
  • Membrane 720 can include one or more polymeric membrane materials having capabilities of limiting analyte flux to active area 718 (i.e., membrane 720 is a mass transport limiting membrane having some permeability for the analyte of interest).
  • the composition and thickness of membrane 720 can vary to promote a desired analyte flux to active area 718, thereby providing a desired signal intensity and stability.
  • Analyte sensor 700a can be operable for assaying an analyte by any of coulometric, amperometric, voltammetric, or potentiometric electrochemical detection techniques.
  • FIGS. 7B and 7C show diagrams of illustrative three-electrode analyte sensor configurations, which are also compatible for use in the disclosure herein.
  • Three-electrode analyte sensor configurations can be similar to that shown for analyte sensor 700a in FIG. 7A, except for the inclusion of additional electrode 717 in analyte sensors 700b and 700c (FIGS. 7B and 7C).
  • additional electrode 717 counter/reference electrode 716 can then function as either a counter electrode or a reference electrode, and additional electrode 717 fulfills the other electrode function not otherwise accounted for.
  • Working electrode 714 continues to fulfill its original function.
  • Additional electrode 717 can be disposed upon either working electrode 714 or electrode 716, with a separating layer of dielectric material in between.
  • dielectric layers 719a, 719b and 719c separate electrodes 714, 716 and 717 from one another and provide electrical isolation.
  • at least one of electrodes 714, 716 and 717 can be located upon opposite faces of substrate 712, as shown in FIG. 7C.
  • electrode 714 working electrode
  • electrode 716 counter electrode
  • electrode 717 reference electrode
  • Reference material layer 730 e.g., Ag/AgCl
  • active area 718 in analyte sensors 700b and 700c can include multiple spots or a single spot.
  • active area 718 can include a redox mediator disclosed herein.
  • analyte sensors 700b and 700c can be operable for assaying an analyte by any of coulometric, amperometric, voltammetric, or potentiometric electrochemical detection techniques.
  • membrane 720 can also overcoat active area 718, as well as other sensor components, in analyte sensors 700b and 700c, thereby serving as a mass transport limiting membrane.
  • the additional electrode 717 can be overcoated with membrane 720.
  • FIGS. 7B and 7C have depicted electrodes 714, 716 and 717 as being overcoated with membrane 720, it is to be recognized that in accordance with the disclosed subject matter, only working electrode 714 is overcoated.
  • the thickness of membrane 720 at each of electrodes 714, 716 and 717 can be the same or different. As in two-electrode analyte sensor configurations (FIG.
  • one or both faces of analyte sensors 700b and 700c can be overcoated with membrane 720 in the sensor configurations of FIGS. 7B and 7C, or the entirety of analyte sensors 700b and 700c can be overcoated. Accordingly, the three-electrode sensor configurations shown in FIGS. 7B and 7C should be understood as being non-limiting of the embodiments disclosed herein, with alternative electrode and/or layer configurations remaining within the scope of the present disclosure.
  • FIG. 8A shows an illustrative configuration for sensor 803 having a single working electrode with two different active areas disposed thereon.
  • FIG. 8A is similar to FIG. 7A, except for the presence of two active areas upon working electrode 814: first active area 818a and second active area 818b, which are responsive to the same or different analytes and are laterally spaced apart from one another upon the surface of working electrode 814.
  • Active areas 818a and 818b can include multiple spots or a single spot configured for detection of each analyte.
  • the composition of membrane 820 can vary or be compositionally the same at active areas 818a and 818b.
  • First active area 818a and second active area 818b can be configured to detect their corresponding analytes at working electrode potentials that differ from one another, as discussed further below.
  • FIGS. 8B and 8C show cross-sectional diagrams of illustrative three-electrode sensor configurations for sensors 804 and 805, respectively, each featuring a single working electrode having first active area 818a and second active area 818b disposed thereon.
  • FIGS. 8B and 8C are otherwise similar to FIGS. 7B and 7C and can be better understood by reference thereto.
  • the composition of membrane 820 can vary or be compositionally the same at active areas 818a and 818b.
  • any one of active areas 818a and 818b can comprise a redox mediator described herein.
  • only one of active areas 2818a and 818b can comprise a redox mediator described herein.
  • only active area 818a includes a redox mediator described herein.
  • only active area 818b includes a redox mediator described herein.
  • both active areas 818a and 818b comprise a redox mediator described herein.
  • the electron transfer agent present in active area 818a is different from the redox mediator present in 818b.
  • the electron transfer agent present in active area 818a is the same redox mediator present in 818b.
  • Illustrative sensor configurations having multiple working electrodes are described in further detail in reference to FIGS. 9-10C. Although the following description is primarily directed to sensor configurations having two working electrodes, it is to be appreciated that more than two working electrodes can be incorporated through extension of the disclosure herein. Additional working electrodes can be used to impart additional sensing capabilities to the analyte sensors beyond just a first analyte and a second analyte.
  • FIG. 9 shows a cross-sectional diagram of an illustrative analyte sensor configuration having two working electrodes, a reference electrode and a counter electrode, which is compatible for use in the disclosure herein.
  • analyte sensor 900 includes working electrodes 904 and 906 disposed upon opposite faces of substrate 902.
  • First active area 910a is disposed upon the surface of working electrode 904, and second active area 910b is disposed upon the surface of working electrode 906.
  • Counter electrode 920 is electrically isolated from working electrode 904 by dielectric layer 922
  • reference electrode 921 is electrically isolated from working electrode 906 by dielectric layer 923.
  • Outer dielectric layers 930 and 932 are positioned upon reference electrode 921 and counter electrode 920, respectively.
  • Membrane 940 can overcoat at least active areas 910a and 910b, according to the disclosed subject matter, with other components of analyte sensor 900 or the entirety of analyte sensor 900.
  • Non-limiting examples of polymers that can be included in membrane 940 are disclosed herein with respect to membrane 720.
  • membrane 940 comprises a copolymer of the present disclosure.
  • membrane 940 comprises a copolymer comprising a first monomer, e.g., an acrylamide (e.g., an N-alkyl acrylamide), and a second monomer comprising a heterocyclecontaining component, e.g., a vinylpyridine, e.g., 4-vinylpyridine.
  • membrane 940 can include a first monomer, e.g., a styrene, and a second monomer comprising a heterocycle-containing component, e.g., a vinylpyridine, e.g., 4- vinylpyridine.
  • membrane 940 can include a polyvinylpyridine-co-styrene copolymer.
  • membrane 940 can include a polyurethane polymer.
  • membrane 940 can be continuous but vary compositionally upon active area 910a and/or upon active area 910b in order to afford different permeability values for differentially regulating the analyte flux at each location.
  • the one or more electrodes can be overcoated with a first membrane portion 940a and/or a second membrane portion 940b.
  • different membrane formulations can be sprayed and/or printed onto the opposing faces of analyte sensor 900. Dip coating techniques can also be appropriate, particularly for depositing at least a portion of a bilayer membrane upon one of active areas 910a and 910b.
  • membrane 940 can be the same or vary compositionally at active areas 910a and 910b.
  • membrane 940 can include a bilayer overcoating active area 910a and be a homogeneous membrane overcoating active area 910b, or membrane 940 can include a bilayer overcoating active areas 910b and be a homogeneous membrane overcoating active area 910a.
  • one of the first membrane portion and the second membrane portion can comprise a bilayer membrane and the other of the first membrane portion and the second membrane portion can comprise a single membrane polymer, according to the subject matter of the present disclosure.
  • an analyte sensor can include more than one membrane 940, e.g., two or more membranes.
  • an analyte sensor can include a membrane that overcoats the one or more active areas, e.g., 910a and 910b, and an additional membrane that overcoats the entire sensor as shown in FIG. 9.
  • a bilayer membrane can be formed over the one or more active areas, e.g., 910a and 910b.
  • the two membranes can have different polymeric compositions.
  • a first membrane can include a copolymer of the present disclosure and the second membrane can include a different polymer.
  • any one of active areas 910a and 910b can comprise an electron transfer agent described herein.
  • only one of active areas 910a and 910b can comprise a redox mediator described herein.
  • only active area 910a includes a redox mediator described herein.
  • only active area 910b includes a redox mediator described herein.
  • both active areas 910a and 910b comprise a redox mediator described herein.
  • the redox mediator present in active area 910a is different from the electron transfer agent present in 910b.
  • the redox mediator present in active area 910a is the same electron transfer agent present in 910b.
  • FIG. 9 Alternative sensor configurations having multiple working electrodes and differing from the configuration shown in FIG. 9 can feature a counter/reference electrode instead of separate counter and reference electrodes 920, 921, and/or feature layer and/or membrane arrangements varying from those expressly depicted.
  • a counter/reference electrode instead of separate counter and reference electrodes 920, 921, and/or feature layer and/or membrane arrangements varying from those expressly depicted.
  • the positioning of counter electrode 920 and reference electrode 921 can be reversed from that depicted in FIG. 9.
  • working electrodes 904 and 906 need not necessarily reside upon opposing faces of substrate 902 in the manner shown in FIG. 9.
  • suitable sensor configurations can feature electrodes that are substantially planar in character, it is to be appreciated that sensor configurations featuring non-planar electrodes can be advantageous and particularly suitable for use in the disclosure herein.
  • substantially cylindrical electrodes that are disposed concentrically with respect to one another can facilitate deposition of a mass transport limiting membrane, as described hereinbelow.
  • concentric working electrodes that are spaced apart along the length of a sensor tail can facilitate membrane deposition through sequential dip coating operations, in a similar manner to that described above for substantially planar sensor configurations.
  • FIGS. 10A-10C show perspective views of analyte sensors featuring two working electrodes that are disposed concentrically with respect to one another. It is to be appreciated that sensor configurations having a concentric electrode disposition but lacking a second working electrode are also possible in the present disclosure.
  • FIG. 10A shows a perspective view of an illustrative sensor configuration in which multiple electrodes are substantially cylindrical and are disposed concentrically with respect to one another about a central substrate.
  • analyte sensor 1000 includes central substrate 1002 about which all electrodes and dielectric layers are disposed concentrically with respect to one another.
  • working electrode 1010 is disposed upon the surface of central substrate 1002, and dielectric layer 1012 is disposed upon a portion of working electrode 1010 distal to sensor tip 1004.
  • Working electrode 1020 is disposed upon dielectric layer 1012, and dielectric layer 1022 is disposed upon a portion of working electrode 1020 distal to sensor tip 1004.
  • Counter electrode 1030 is disposed upon dielectric layer 1022, and dielectric layer 1032 is disposed upon a portion of counter electrode 1030 distal to sensor tip 1004.
  • Reference electrode 1040 is disposed upon dielectric layer 1032, and dielectric layer 1042 is disposed upon a portion of reference electrode 1040 distal to sensor tip 1004. As such, exposed surfaces of working electrode 1010, working electrode 1020, counter electrode 1030, and reference electrode 1040 are spaced apart from one another along longitudinal axis B of analyte sensor 1000.
  • first active areas 1014a and second active areas 1014b which are responsive to different analytes, are disposed upon the exposed surfaces of working electrodes 1010 and 1020, respectively, thereby allowing contact with a fluid to take place for sensing.
  • active areas 1014a and 1014b have been depicted as three discrete spots in FIG. 10 A, it is to be appreciated that fewer or greater than three spots, including a continuous layer of active area, can be present in alternative sensor configurations.
  • any one of active areas 1014a and 1014b can comprise an electron transfer agent described herein.
  • only one of active areas 1014a and 1014b can comprise a redox mediator described herein.
  • only active area 1014a includes a redox mediator described herein.
  • only active area 1014b includes a redox mediator described herein.
  • both active areas 1014a and 1014b comprise a redox mediator described herein.
  • the redox mediator present in active area 1014a is different from the electron transfer agent present in 1014b.
  • the redox mediator present in active area 1014a is the same electron transfer agent present in 1014b.
  • FIG. 10A sensor 1000 is partially coated with membrane 1050 upon working electrodes 1010 and 1020 and active areas 1014a and 1014b disposed thereon.
  • FIG. 10B shows an alternative sensor configuration in which the substantial entirety of sensor 1001 is overcoated with membrane 1050.
  • Membrane 1050 can be the same or vary compositionally at active areas 1014a and 1014b.
  • membrane 1050 can include a bilayer overcoating active area 1014a and be a homogeneous membrane overcoating active area 1014b.
  • Nonlimiting examples of polymers that can be included in membrane 1050 are disclosed herein with respect to membrane 720 and membrane 940.
  • membrane 1050 comprises a copolymer of the present disclosure.
  • membrane 1050 comprises a copolymer comprising a first monomer, e.g., an acrylamide e.g., an N-alkyl acrylamide), and a second monomer comprising a heterocyclecontaining component, e.g., a vinylpyridine, e.g., 4-vinylpyridine.
  • membrane 1050 can include a first monomer, e.g., a styrene, and a second monomer comprising a heterocycle-containing component, e.g., a vinylpyridine, e.g., 4- vinylpyridine.
  • membrane 1050 can include a polyvinylpyridine-co-styrene copolymer.
  • membrane 940 can include a polyurethane polymer.
  • an analyte sensor can further include an interference domain as shown in FIG. 20.
  • FIG. 20 illustrates an exemplary cross-sectional diagram of an in vivo portion of an analyte sensor.
  • an in vivo portion of an analyte sensor can further include an interference domain (e.g., shown as 2003 of FIG. 20).
  • the interference domain can include a polymer domain that restricts the flow of one or more interferants, e.g., to the surface of the working electrode.
  • the interference domain can function as a molecular sieve that allows analytes and other substances that are to be measured by the working electrode to pass through, while preventing passage of other substances such as interferents.
  • the interferents can affect the signal obtained at the working electrode.
  • Non-limiting examples of interferents can include acetaminophen, ascorbate, ascorbic acid, bilirubin, cholesterol, creatinine, dopamine, ephedrine, ibuprofen, L-dopa, methyldopa, salicylate, tetracycline, tolazamide, tolbutamide, triglycerides, urea, and uric acid.
  • the interference domain 2003 is located between the working electrode (e.g., the electroactive surface of the working electrode 2002) and the active area 2004, e.g., as shown in FIG. 20.
  • the interference domain is located between the active area 2004 and the membrane 2005.
  • the interference domain is part of the membrane and not a separate membrane. Alternatively, the interference domain is a separate from the membrane.
  • the interference domain can include a thin, hydrophobic membrane that is non-swellable and restricts diffusion of high molecular weight species.
  • the interference domain can be permeable to relatively low molecular weight substances, such as hydrogen peroxide, while restricting the passage of higher molecular weight substances, such as ketones, glucose, acetaminophen and/or ascorbic acid.
  • Non-limiting examples of polymers that can be utilized in the interference domain can include polyurethanes, polymers having pendant ionic groups, and polymers having controlled pore size.
  • the interference domain can be formed from one or more cellulosic derivatives.
  • Non-limiting examples of cellulosic derivatives include polymers such as cellulose acetate, cellulose acetate butyrate, 2-hydroxyethyl cellulose, cellulose acetate phthalate, cellulose acetate propionate, cellulose acetate trimellitate and the like.
  • FIGS. 10A and 10B can differ from that expressly depicted.
  • the positions of counter electrode 1030 and reference electrode 1040 can be reversed from the depicted configurations in FIGS. 10A and 10B.
  • the positions of working electrodes 1010 and 1020 are not limited to those that are expressly depicted in FIGS. 10A and 10B.
  • FIG. 10C shows an alternative sensor configuration to that shown in FIG. 10B, in which sensor 1005 contains counter electrode 1030 and reference electrode 1040 that are located more proximal to sensor tip 1004 and working electrodes 1010 and 1020 that are located more distal to sensor tip 1004.
  • Sensor configurations in which working electrodes 1010 and 1020 are located more distal to sensor tip 1004 can be advantageous by providing a larger surface area for deposition of active areas 1014a and 1014b (five discrete sensing spots illustratively shown in FIG. 10C), thereby facilitating an increased signal strength in some cases.
  • central substrate 1002 can be omitted in any concentric sensor configuration disclosed herein, wherein the innermost electrode can instead support subsequently deposited layers.
  • one or more electrodes of an analyte sensor described herein can be a wire electrode.
  • the sensor tail (e.g., in vivo portion) 1800 can include a working electrode 1802 and a reference electrode 1803 disposed upon the working electrode, e.g., disposed coaxially over the working electrode.
  • the reference electrode can be helically wound around the working electrode.
  • an insulator e.g., 1804 can be disposed between the working and reference electrodes.
  • portions of the electrodes can be exposed to allow reaction of the one or more enzymes with an analyte on the electrode (e.g. , 1802).
  • the electroactive surface e.g., carbon or platinum electroactive surface
  • the wire working electrode can be exposed at the distal tip 1802 or exposed at the proximal end 1805.
  • a sensing layer is disposed over the exposed electroactive surface 1802.
  • each electrode can be formed from a fine wire with a diameter of from about 0.001 inches or less to about 0.010 inches or more.
  • the working electrode can have a diameter of from about 0.001 inches or less to about 0.010 inches or more, e.g., from about 0.002 inches to about 0.008 inches or from about 0.004 inches to about 0.005 inches.
  • an electrode can be formed from a plated insulator, a plated wire or bulk electrically conductive material.
  • the working electrode can comprise a wire formed from a conductive material, such as platinum, platinum-iridium, palladium, graphite, gold, carbon, conductive polymer, alloys or the like.
  • the conductive material can be a permeable conductive material.
  • the electrodes can be formed by a variety of manufacturing techniques (e.g., bulk metal processing, deposition of metal onto a substrate or the like), the electrodes can be formed from plated wire (e.g., platinum on steel wire) or bulk metal (e.g., platinum wire).
  • the electrode can be formed from tantalum wire, e.g., covered with platinum.
  • the reference electrode can function as a reference electrode alone or as a dual reference and counter electrode.
  • the reference electrode can be formed from silver, silver/silver chloride, or the like.
  • the reference electrode can be juxtaposed and/or twisted with or around the working electrode.
  • the reference electrode is helically wound around the working electrode.
  • the assembly of wires can be coated or adhered together with an insulating material so as to provide an insulating attachment.
  • additional electrodes can be included in the sensor tail (e.g., in vivo portion).
  • a three- electrode system a working electrode, a reference electrode and a counter electrode
  • an additional working electrode e.g., an electrode for detecting a second analyte
  • the sensor comprises two working electrodes
  • the two working electrodes can be juxtaposed around which the reference electrode is disposed upon (e.g., helically wound around the two or more working electrodes).
  • the two or more working electrodes can extend parallel to each other.
  • the reference electrode is disposed coaxially over the working electrode (e.g. , the reference electrode is coiled around the working electrode) and extends towards the distal end (ie., in vivo end) of the sensor tail.
  • the reference electrode can extend (e.g., helically) to the exposed region of the working electrode.
  • one or more working electrodes are helically wound around a reference electrode.
  • the working electrodes can be formed in a double-, triple-, quad- or greater helix configuration along the length of the sensor tail (for example, surrounding a reference electrode, insulated rod or other support structure).
  • the electrodes e.g., two or more working electrodes, are coaxially formed.
  • the electrodes all share the same central axis.
  • the working electrode comprises a tube with a reference electrode disposed or coiled inside, including an insulator therebetween.
  • the reference electrode comprises a tube with a working electrode disposed or coiled inside, including an insulator therebetween.
  • a polymer (e.g., insulating) rod can be provided, wherein the one or more electrodes (e.g., one or more electrode layers) are disposed upon (e.g., by electro-plating).
  • a metallic (e.g., steel or tantalum) rod or wire is provided, coated with an insulating material (described herein), onto which the one or more working and reference electrodes are disposed upon.
  • the present disclosure provides a sensor, e.g., a sensor tail, that comprises one or more tantalum wires, where a conductive material is disposed upon a portion of the one or more tantalum wires to function as a working electrode.
  • a sensor e.g., a sensor tail
  • the platinum - clad tantalum wire is covered with an insulating material (e.g., 1801 and 1804 of FIG. 18), where the insulating material is partially covered with a silver/silver chloride composition to function as a reference and/or counter electrode (e.g., 1803 of FIG. 18).
  • a portion of the insulator e.g., shown as 1801 in FIG. 18
  • a portion of the insulator can be stripped or otherwise removed to expose the electroactive surface of the working electrode, e.g., shown as 1802 in FIG. 18.
  • a portion of the insulator can be removed by hand, excimer lasing, chemical etching, laser ablation, gritblasting or the like.
  • a portion of the electrode can be masked prior to depositing the insulator to maintain an exposed electroactive surface area.
  • the portion of the insulator that is stripped and/or removed can be from about 0.1 mm or less to about 2 mm or more in length, e.g., from about 0.5 mm to about 0.75 mm in length.
  • the insulator can be a non-conductive polymer.
  • the insulator can comprise parylene, fluorinated polymers, polyethylene terephthalate, polyvinylpyrrolidone, polyurethane, polyimide, other nonconducting polymers, or any suitable combination thereof. Glass or ceramic materials can also be used in the insulator layer.
  • an in vivo portion of the analyte sensor 1900 and 2000 can include a wire working electrode 1901 and 2001 as shown in FIGS. 19 and 20.
  • the working 1901 or 2001 can include an electroactive surface 1902 or 2002, e.g. , a carbon electroactive surface or a platinum electroactive surface.
  • sensing layer 1903 can be disposed upon the electroactive surface 1902.
  • interference domain 2003 is disposed upon electroactive surface 2002 and sensing layer 2004 can be disposed upon interference domain 2003 as shown in FIG. 20.
  • a membrane 1904 and 2005 can be disposed upon sensing layer 1903 and 2004 as shown in FIGS. 19 and 20.
  • membrane 1904 and 2005 is an analyte limiting barrier.
  • Biochemical sensors can be described by one or more sensing characteristics.
  • a common sensing characteristic is referred to as the biochemical sensor’s sensitivity, which is a measure of the sensor's responsiveness to the concentration of the chemical or composition it is designed to detect.
  • this response can be in the form of an electrical current (amperometric) or electrical charge (coulometric).
  • the response can be in a different form, such as a photonic intensity (e.g., optical light).
  • the sensitivity of a biochemical analyte sensor can vary depending on a number of factors, including whether the sensor is in an in vitro state or an in vivo state.
  • FIG. 11 is a graph depicting the in vitro sensitivity of an amperometric analyte sensor.
  • the in vitro sensitivity can be obtained by in vitro testing the sensor at various analyte concentrations and then performing a regression (e.g., linear or non-linear) or other curve fitting on the resulting data.
  • the analyte level that corresponds to a given current can be determined from the slope and intercept of the sensitivity.
  • Sensors with a non-linear sensitivity require additional information to determine the analyte level resulting from the sensor's output current, and those of ordinary skill in the art are familiar with manners by which to model non-linear sensitivities.
  • the in vitro sensitivity can be the same as the in vivo sensitivity, but in other examples a transfer (or conversion) function is used to translate the in vitro sensitivity into the in vivo sensitivity that is applicable to the sensor's intended in vivo use.
  • Calibration is a technique for improving or maintaining accuracy by adjusting a sensor's measured output to reduce the differences with the sensor's expected output.
  • One or more parameters that describe the sensor's sensing characteristics, like its sensitivity, are established for use in the calibration adjustment.
  • Certain in vivo analyte monitoring systems require calibration to occur after implantation of the sensor into the user or patient, either by user interaction or by the system itself in an automated fashion.
  • the user performs an in vitro measurement (e.g., a blood glucose (BG) measurement using a finger stick and an in vitro test strip) and enters this into the system, while the analyte sensor is implanted.
  • the system compares the in vitro measurement with the in vivo signal and, using the differential, determines an estimate of the sensor's in vivo sensitivity.
  • the in vivo sensitivity can then be used in an algorithmic process to transform the data collected with the sensor to a value that indicates the user's analyte level.
  • This and other processes that require user action to perform calibration are referred to as “user calibration.”
  • Systems can require user calibration due to instability of the sensor's sensitivity, such that the sensitivity drifts or changes over time.
  • multiple user calibrations e.g., according to a periodic (e.g., daily) schedule, variable schedule, or on an as-needed basis
  • a degree of user calibration for a particular implementation, generally this is not preferred as it requires the user to perform a painful or otherwise burdensome BG measurement and can introduce user error.
  • Some in vivo analyte monitoring systems can regularly adjust the calibration parameters through the use of automated measurements of characteristics of the sensor made by the system itself (e.g., processing circuitry executing software).
  • the repeated adjustment of the sensor's sensitivity based on a variable measured by the system (and not the user) is referred to generally as “system” (or automated) calibration, and can be performed with user calibration, such as an early BG measurement, or without user calibration.
  • system calibrations are typically necessitated by drift in the sensor's sensitivity over time.
  • the embodiments described herein can be used with a degree of automated system calibration, preferably the sensor’s sensitivity is relatively stable over time such that post-implantation calibration is not required.
  • Factory calibration refers to the determination or estimation of the one or more calibration parameters prior to distribution to the user or healthcare professional (HCP).
  • the calibration parameter can be determined by the sensor manufacturer (or the manufacturer of the other components of the sensor control device if the two entities are different).
  • Many in vivo sensor manufacturing processes fabricate the sensors in groups or batches referred to as production lots, manufacturing stage lots, or simply lots. A single lot can include thousands of sensors.
  • Sensors can include a calibration code or parameter which can be derived or determined during one or more sensor manufacturing processes and coded or programmed, as part of the manufacturing process, in the data processing device of the analyte monitoring system or provided on the sensor itself, for example, as a bar code, a laser tag, an RFID tag, or other machine-readable information provided on the sensor.
  • a calibration code or parameter which can be derived or determined during one or more sensor manufacturing processes and coded or programmed, as part of the manufacturing process, in the data processing device of the analyte monitoring system or provided on the sensor itself, for example, as a bar code, a laser tag, an RFID tag, or other machine-readable information provided on the sensor.
  • the calibration code or parameter can be automatically transmitted or provided to the data processing device in the analyte monitoring system.
  • Some in vivo analyte monitoring system operate with a sensor that can be one or more of factory calibrated, system calibrated, and/or user calibrated.
  • the sensor can be provided with a calibration code or parameter which can allow for factory calibration. If the information is provided to a receiver (for example, entered by a user), the sensor can operate as a factory calibrated sensor. If the information is not provided to a receiver, the sensor can operate as a user calibrated sensor and/or a system calibrated sensor.
  • programming or executable instructions can be provided or stored in the data processing device of the analyte monitoring system, and/or the receiver/controller unit, to provide a time varying adjustment algorithm to the in vivo sensor during use. For example, based on a retrospective statistical analysis of analyte sensors used in vivo and the corresponding glucose level feedback, a predetermined or analytical curve or a database can be generated which is time based, and configured to provide additional adjustment to the one or more in vivo sensor parameters to compensate for potential sensor drift in stability profile, or other factors.
  • the analyte monitoring system can be configured to compensate or adjust for the sensor sensitivity based on a sensor drift profile.
  • a time varying parameter P(t) can be defined or determined based on analysis of sensor behavior during in vivo use, and a time varying drift profile can be determined.
  • the compensation or adjustment to the sensor sensitivity can be programmed in the receiver unit, the controller or data processor of the analyte monitoring system such that the compensation or the adjustment or both can be performed automatically and/or iteratively when sensor data is received from the analyte sensor.
  • the adjustment or compensation algorithm can be initiated or executed by the user (rather than selfinitiating or executing) such that the adjustment or the compensation to the analyte sensor sensitivity profile is performed or executed upon user initiation or activation of the corresponding function or routine, or upon the user entering the sensor calibration code.
  • each sensor in the sensor lot (in some instances not including sample sensors used for in vitro testing) can be examined non- destructively to determine or measure its characteristics such as membrane thickness at one or more points of the sensor, and other characteristics including physical characteristics such as the surface area/volume of the active area can be measured or determined.
  • Such measurement or determination can be performed in an automated manner using, for example, optical scanners or other suitable measurement devices or systems, and the determined sensor characteristics for each sensor in the sensor lot is compared to the corresponding mean values based on the sample sensors for possible correction of the calibration parameter or code assigned to each sensor.
  • the sensitivity is approximately inversely proportional to the membrane thickness, such that, for example, a sensor having a measured membrane thickness of approximately 4% greater than the mean membrane thickness for the sampled sensors from the same sensor lot as the sensor, the sensitivity assigned to that sensor is the mean sensitivity determined from the sampled sensors divided by 1.04.
  • the sensitivity is approximately proportional to active area of the sensor, a sensor having measured active area of approximately 3% lower than the mean active area for the sampled sensors from the same sensor lot, the sensitivity assigned to that sensor is the mean sensitivity multiplied by 0.97.
  • the assigned sensitivity can be determined from the mean sensitivity from the sampled sensors, by multiple successive adjustments for each examination or measurement of the sensor.
  • examination or measurement of each sensor can additionally include measurement of membrane consistency or texture in addition to the membrane thickness and/or surface are or volume of the active sensing area.
  • the membrane includes a resistance domain.
  • FIG. 12 illustrates a system 1200 for estimating membrane thickness by electrochemical measurements, in accordance with the disclosed subject matter.
  • System 1200 or portions thereof may be associated with an entity, which may include any entity, such as a business, company, or enterprise, that estimates membrane thickness by electrochemical measurements.
  • the entity may be a medical product/device company, a diagnostics company, a pharmaceutical company, and the like.
  • the components of system 1200 may include any suitable combination of hardware, firmware, and software.
  • the components of system 1200 may use one or more elements of the computer system of FIG. 16.
  • system 1200 includes a sensor 1201, a transmitter unit 1202 coupled to the sensor 1201, and a receiver unit 1204 which is configured to communicate with transmitter unit 1202 via a communication link 1203.
  • Receiver unit 1204 may be further configured to transmit data to a data processing terminal 1205 for evaluating the data received by receiver unit 1204.
  • the data processing terminal in accordance with the disclosed subject matter can be configured to receive data directly from transmitter unit 1202 via a communication link 1206 which may optionally be configured for bi-directional communication.
  • FIGS. 13A and 13B illustrate the process of adding a capping membrane of the system.
  • FIG 13 A illustrates a sensor tip 1301 for sensor 1201 of FIG. 12, in accordance with the disclosed subject matter.
  • the sensor tip 1301 includes a membrane coating 1302 and a working electrode 1303 before an application of a capping membrane.
  • FIG. 13B shows the addition of the capping membrane 1304 to the system.
  • the membrane coating 1302 serves as a glucose limiting barrier around sensor tip 1301.
  • the capping membrane 1304 holds the analyte (e.g., glucose).
  • membrane coating 1302 comprises an interference domain. In accordance with the disclosed subject matter, membrane coating 1302 comprises an analyte limiting barrier. In accordance with the disclosed subject matter, membrane coating 1302 comprises a sensing layer. In accordance with the disclosed subject matter, membrane coating 1302 include two or more of an interference domain, a sensing layer and an analyte limiting barrier. For example, but not by way of limitation, membrane 1301 includes an interference domain and an analyte limiting barrier. Alternatively or additionally, membrane coating 1302 includes an interference domain and a sensing layer. In accordance with the disclosed subject matter, membrane coating 1302 includes an interference domain, a sensing layer and an analyte limiting barrier.
  • the capping membrane 1304 comprises a hydrogel membrane such as, but not limited to a P4VP -based membrane, a P4VP-co-PSS- based membrane, a polyvinylpyrrolidone-based membrane, and the like.
  • the working electrode 203 can include a specific type of electrode with well-defined materials that has a known stable potential to which other electrode potentials are referenced.
  • working electrode 1303 represents a sensing layer where signals may be generated and/or detected.
  • the capping membrane 1304 can comprise a thin permeable membrane (e.g., 1 to 50 microns).
  • a permeability measurement of the capping membrane to the analyte can be higher (e.g., 2-10 times greater) than a permeability measurement of the membrane coating to the analyte (e.g., glucose).
  • electrochemical measurements are caused by analyte diffusion (e.g., glucose) from the capping membrane 1304 into the underlaying membrane coating 1302.
  • the electrochemical measurements can cause a signature response that is dependent on the thickness of underlying membrane coating 1302.
  • the analyte can be embedded into the capping membrane 1304 during the production process of system 1200.
  • Analytes can include, but are not limited to, acetyl choline, amylase, bilirubin, carbon dioxide, cholesterol, chorionic gonadotropin, glycosylated hemoglobin (HbAlc), creatine kinase (e.g., CK-MB), creatine, creatinine, DNA, fructosamine, glucose, glucose derivatives, glutamine, growth hormones, hormones, ketones, ketone bodies, lactate, oxygen, peroxide, prostate-specific antigen, proteins, prothrombin, RNA, thyroid stimulating hormone, troponin, and any combination thereof.
  • HbAlc glycosylated hemoglobin
  • CK-MB creatine kinase
  • the glucose response as the capping membrane 1304 thickens shows the effect of analyte (e.g., glucose) diffusion from the capping membrane 1304 (P4VP-CO-PSS membrane) into the membrane coating 1302 and finally to the sensing layer, where the signals are generated.
  • analyte e.g., glucose
  • the signals can include underlying analyte signals in additional to the signal generated by the analyte in the capping membrane 1304.
  • the generated signal can be a sum of the glucose in the interstitial fluid and the glucose in the capping membrane 1304.
  • the signal caused by the underlying analyte signal can be removed (e.g., subtracted) to determine the signal generated by the analyte in the capping membrane 1304.
  • a decaying curve can be modeled and subtracted from the sensor signal to provide underlying analyte signal.
  • This baseline correction can represent the amount of analyte (e.g., glucose) in the solution or interstitial fluid.
  • the glucose in the capping membrane 1304 is used up, and the sensor signal can represent the glucose level in the interstitial fluid.
  • This measured signal can be subtracted from the initial signal to provide the response due to the analyte in the capping membrane 1304, which can be used to determine the membrane thickness.
  • the membrane polymer preparation of membrane coating 1302 comprised a predetermined amount of a formulation called 10Q5, although any other suitable formulation may be used.
  • Formulation 10Q5 is described in U.S. patent application Ser. No. 11/734,272, the disclosure of which is incorporated herein by reference in its entirety.
  • the glucose diffusion is omnidirectional, such that part of the glucose diffuses into the media surrounding sensor 1201 as well without reaching the sensor 1201.
  • the current generated is directly proportional to the amount of glucose that is able to diffuse from the capping layer to the working electrode.
  • the sensor tips 1301 are inserted into the solution of membrane coating 1302 and withdrawn at a well-defined velocity.
  • Well-defined in this context indicates that the velocity is specified and the equipment is verified and/or validated to execute the specified velocity.
  • the process is repeated until the desired membrane thickness is achieved.
  • the membrane coating 1302 is then cured in an environmental chamber.
  • a thicker membrane e.g., 6 dips
  • a delayed signal e.g., 5 dips.
  • FIG. 15 illustrates a graph 1500 of the obtained charge due to glucose diffusion, in accordance with the disclosed subject matter.
  • Graph 1500 includes an x-axis representing 1 over the membrane coating 1302 (i.e., the inverse of membrane thickness in micrometers) and a y-axis representing the charge (in millicoulombs (mC)).
  • the obtained charge illustrated in FIG. 15 is due at least in part to glucose diffusion from the capping membrane 1304 to the sensing layer of sensor 1201 as a function of the thickness of membrane coating 1302. In other examples, the charge can be due to natural glucose levels obtained in vivo.
  • Graph 1500 of FIG. 15 shows a plot of the integrated charge between 4 and 10 minutes (0.07 — 0.17 hours as illustrated by the x-axis of FIG.
  • This initial current measurement correlates with the actual thickness of the membrane coating 1302 and can lead to an in-vivo membrane thickness/status checkup.
  • the shape of the sensor current over time is indicative of the membrane thickness.
  • an increase in current after the initial decay happens only with thinner membranes.
  • this sensor configuration may be used for a check of the function of the sensor 1201. For example, when using a thinner membrane sensor configuration, the sensor current after insertion in the body shows a local maximum, as illustrated in FIG. 14 for 3 dips membrane coating + 5 dips capping membrane and for 3 dips membrane coating + 6 dips capping membrane, shortly after the initial current decay. If that local maximum is not present, the sensor 1201 may not be inserted correctly or may not function properly. Algorithms may then trigger a warning and ask for removing and/or replacing of the sensor 1201.
  • Graph 1500 shows the direct relation between the total charge passed through sensor 1201 for a given time (y-axis) correlated to the inverse of the thickness of the membrane coating 1302 (x-axis). As the membrane becomes thicker (left side of x-axis), less current is passed at the beginning of the wear. Increasing the thickness of the capping membrane from 5 dips to 6 dips increases the amount of total loaded glucose. This in turn increases the total charge passed, as illustrated in FIG. 15 by the lower dotted line (corresponding to 5 dips of the capping membrane solution) and the upper dotted line (corresponding to 6 dips of the capping membrane solution) of graph 1500.
  • FIG. 16 shows an example computer system 1600 that may be used by the systems and methods described herein.
  • system 1200 of FIG. 12 may include one or more interface(s) 1610, processing circuitry 1620, memory(ies) 1630, and/or other suitable element(s).
  • Interface 1610 receives input, sends output, processes the input and/or output, and/or performs other suitable operation.
  • Interface 1610 may comprise hardware and/or software.
  • Processing circuitry 1620 performs or manages the operations of the component.
  • Processing circuitry 1620 may include hardware and/or software. Examples of a processing circuitry include one or more computers, one or more microprocessors, one or more applications, etc.
  • processing circuitry 1620 executes logic (e.g., instructions) to perform actions (e.g., operations), such as generating output from input.
  • the logic executed by processing circuitry 1620 may be encoded in one or more tangible, non-transitory computer readable media (such as memory 1630).
  • the logic may comprise a computer program, software, computer executable Instructions, and/or instructions capable of being executed by a computer.
  • the operations of the subject matter can be performed by one or more computer readable media storing, embodied with, and/or encoded with a computer program and/or having a stored and/or an encoded computer program.
  • Memory 1630 (or memory unit) stores information.
  • Memory 1630 may include one or more non-transitory, tangible, computer-readable, and/or computer-executable storage media.
  • Examples of memory 1630 include computer memory (for example, RAM or ROM), mass storage media (for example, a hard disk), removable storage media (for example, a Compact Disk (CD) or a Digital Video Disk (DVD)), database and/or network storage (for example, a server), and/or other computer-readable medium.
  • FIG. 17 illustrates an example method 1700 for estimating membrane thickness by electrochemical measurements, in accordance with the disclosed subject matter.
  • Method 1700 starts at step 1705.
  • a tip of a sensor e.g., sensor 1201 of FIG. 12
  • a membrane coating e.g., membrane coating 1302 of FIG. 13
  • the sensor can have a working electrode such that the membrane coating is disposed over the working electrode.
  • Coating the tip of the sensor with the membrane coating can include dipping the tip of the sensor in an analyte limiting barrier.
  • the analyte limiting barrier can include a glucose limiting barrier.
  • Method 1700 then moves from step 1710 to step 1715.
  • analyte is embedded into a capping membrane (e.g., capping membrane 1304 of FIG. 13).
  • the analyte may include glucose, ketone, lactate, or any other suitable type of analyte.
  • Method 1700 then moves from step 1715 to step 1720.
  • the capping membrane is disposed over at least a portion of the tip (e.g., sensor tip 1301 of FIG. 13) of the sensor.
  • the capping membrane may include a P4VP-co-PSS membrane or a polyurethane based membrane. Disposing the capping membrane over at least a portion of the tip of the sensor can include disposing the capping membrane over the membrane coating. Method 1700 then moves from step 1720 to step 1725.
  • a working electrode of the sensor detects a first plurality of signals over a first period of time.
  • the working electrode can represent a sensing layer where signals can be generated and/or detected.
  • Method 1700 then moves from step 1725 to step 1730, where a first current measurement is determined from the first plurality of signals.
  • Method 1700 then moves from step 1730 to step 1735.
  • the working electrode of the sensor detects a second plurality of signals over a second period of time. For example, the second time period can occur about 30 minutes after the first time period.
  • Method 1700 then moves from step 1735 to step 1740, where a second current measurement is determined from the second plurality of signals.
  • Method 1700 then moves from step 1740 to step 1745.
  • a third current is estimated by subtracting the second current from the first current. Method 1700 then moves from step 1745 to step 1750.
  • a thickness of the membrane coating is estimated based at least on the third current measurement.
  • the third current measurement can represent current generated by diffusion of the analyte from the capping membrane into the membrane coating, as illustrated in FIG. 14.
  • Method 1700 then moves from step 1750 to step 1755, where method 1700 ends.
  • this disclosure describes and illustrates particular steps of method 1700 of FIG. 17 as occurring in a particular order, this disclosure contemplates any suitable steps of method 1700 of FIG. 17 occurring in any suitable order.
  • this disclosure describes and illustrates an example method 1700 for estimating membrane thickness by electrochemical measurements, including the particular steps of method 1700 of FIG. 17, this disclosure contemplates any suitable method for estimating membrane thickness by electrochemical measurements, including any suitable steps, which may include all, some, or none of the steps of method 1700 of FIG. 17, where appropriate.
  • FIG. 17 describes and illustrates particular components, devices, or systems carrying out particular actions, this disclosure contemplates any suitable combination of any suitable components, devices, or systems carrying out any suitable actions.
  • references to an apparatus, system, or a component of an apparatus or system being adapted to, arranged to, capable of, configured to, enabled to, operable to, or operative to perform a particular function encompasses that apparatus, system, component, whether or not it or that particular function is activated, turned on, or unlocked, as long as that apparatus, system, or component is so adapted, arranged, capable, configured, enabled, operable, or operative. Additionally, although this disclosure describes or illustrates particular embodiments as providing particular advantages, particular embodiments may provide none, some, or all of these advantages.
  • a method for estimating a thickness of a membrane coating on an in vivo sensor comprising: providing a sensor having a working electrode; coating a tip of the sensor with a membrane coating such that the membrane coating is disposed over the working electrode; embedding analyte into a capping membrane; disposing the capping membrane over at least a portion of the tip of the sensor; detecting, by the working electrode, a plurality of signals over a period of time; determining current measurements from the plurality of signals; and estimating a thickness of the membrane coating at least in part by analyzing a relationship of the current measurements to the period of time.
  • Clause 4 The method of one of clauses 1-3, wherein the analyte comprises: glucose; ketone, or lactate.
  • Clause 5 The method of any one of clauses 1-4, wherein a permeability measurement of the capping membrane to the analyte is higher than a permeability measurement of the membrane coating to the analyte.
  • Clause 6 The method of any one of clauses 1-5, wherein the capping membrane comprises a P4VP-CO-PSS membrane.
  • Clause 7 The method of any one of clauses 1-6, wherein the disposing the capping membrane over at least a portion of the tip of the sensor includes disposing the capping membrane over the membrane coating. Clause 8. The method of any one of clauses 1-7, wherein the current measurements represent current generated by diffusion of the analyte from the capping membrane into the membrane coating.
  • a system comprising: a sensor having a working electrode operable to detect a plurality of signals over a period of time; a membrane coating disposed over a tip of the sensor such that the membrane coating is disposed over the working electrode; a capping membrane embedded with analyte, wherein the capping membrane is disposed over at least a portion of the tip of the sensor; and a processor operable to: determine current measurements from the plurality of signals; and estimate a thickness of the membrane coating at least in part by analyzing a relationship of the current measurements to the period of time.
  • Clause 14 The system of clause 13, wherein the membrane coating comprises an analyte limiting barrier.
  • Clause 15 The system of any one of clauses 13-14, wherein the analyte limiting barrier comprises a glucose limiting barrier.
  • Clause 17 The system of any one of clauses 13-16, wherein the analyte comprises: glucose; ketone, or lactate.
  • Clause 18 The system of any one of clauses 13-17, wherein a permeability measurement of the capping membrane is higher than a permeability measurement of the membrane coating.
  • Clause 19 The system of any one of clauses 13-18, wherein the capping membrane comprises a P4VP-CO-PSS membrane or a polyurethane membrane.
  • Clause 20 The system of any one of clauses 13-19, wherein the capping membrane is disposed over at least a portion of the membrane coating.
  • Clause 22 The system of any one of clauses 13-21, wherein disposing the capping membrane over at least a portion of the tip of the sensor comprises dipping the tip of the sensor in a P4VP- co-PSS membrane solution.
  • Clause 23 The system of any one of clauses 13-22, wherein analyzing the relationship of the current measurements to the period of time comprises: integrating the current measurements over the period of time; and identifying a local maximum current over the period of time.
  • Clause 24 The system of any one of clauses 13-23, further comprising: detecting, by the working electrode, a second plurality of signals over a second period of time; determining a second current measurement from the second plurality of signals; determining a third current measurement by subtracting the second current measurement from the first current measurement; and estimating a thickness of the membrane coating based at least in part on the third current measurement, wherein the second time period is after the first time period.
  • a sensor comprising: a working electrode, wherein the working electrode is configured to detect a plurality of signals over a period of time; a membrane coating disposed over the working electrode; a capping membrane having analyte embedded therein, wherein the capping membrane is disposed over at least a portion of the tip; and a processor configured to: determine current measurements from the plurality of signals; and estimate a thickness of the membrane coating at least in part by analyzing a relationship of the current measurements to the period of time.
  • Clause 26 The sensor of clause 25, wherein the membrane coating comprises an analyte limiting barrier.
  • Clause 27 The sensor of any one of clauses 25-26, wherein the analyte limiting barrier comprises a glucose limiting barrier.
  • Clause 28 The sensor of any one of clauses 25-27, wherein the membrane coating comprises an interference domain.
  • Clause 29 The sensor of any one of clauses 25-28, wherein the analyte comprises: glucose; ketone, or lactate.
  • Clause 30 The sensor of any one of clauses 25-29, wherein a permeability measurement of the capping membrane is higher than a permeability measurement of the membrane coating.
  • Clause 31 The sensor of any one of clauses 25-30, wherein the capping membrane comprises a P4VP-CO-PSS membrane or a polyurethane membrane.
  • Clause 32 The sensor of any one of clauses 25-31, wherein the capping membrane is disposed over at least a portion of the membrane coating.
  • Clause 34 The sensor of any one of clauses 25-33, wherein disposing the capping membrane over at least a portion of the tip of the sensor comprises dipping the tip of the sensor in a P4VP- co-PSS membrane solution.
  • a method for estimating a thickness of a membrane coating on an in vivo sensor comprising: coating a tip of a sensor with a membrane coating; embedding glucose into a capping membrane; disposing the capping membrane over at least a portion of the tip of the sensor; detecting, by the working electrode, a plurality of signals over a period of time; determining current measurements from the plurality of signals; and estimating a thickness of the membrane coating at least in part by analyzing a relationship of the current measurements to the period of time.
  • Clause 38 The method of clause 37, wherein the current measurements represent current generated by diffusion of the glucose from the capping membrane into the membrane coating.
  • Clause 39 The sensor of any one of clauses 37-38, further comprising: detecting, by the working electrode, a second plurality of signals over a second period of time; determining a second current measurement from the second plurality of signals; determining a third current measurement by subtracting the second current measurement from the first current measurement; and estimating a thickness of the membrane coating based at least in part on the third current measurement, wherein the second time period is after the first time period.
  • a method comprising: providing a sensor having a working electrode; coating a tip of the sensor with a membrane coating such that the membrane coating is disposed over the working electrode; embedding analyte into a capping membrane; disposing the capping membrane over at least a portion of the tip of the sensor; detecting, by a working electrode, a first plurality of signals over a first period of time; determining a first current measurement from the first plurality of signals; detecting, by the working electrode, a second plurality of signals over a second period of time; determining a second current measurement from the second plurality of signals; and determining a third current measurement by subtracting the second current measurement from the first current measurement; and estimating a thickness of the membrane coating based at least in part on the third current measurement; wherein the second time period is after the first time period.
  • Clause 41 The method of clause 40, wherein the second time period is approximately 30 minutes after the first time period.
  • An analyte monitoring system for estimating membrane thickness by electrochemical measurement, comprising: a sensor; a sensor control device, the sensor control device including the sensor and a processor; a sensor applicator operable to deliver the sensor control device to a monitoring location on a user’s skin where the sensor is maintained in position for a period of time; and a reader device operable to communicate with the sensor control device, the reader device including a display, an input component, and a processing core; wherein: the sensor has a working electrode; a membrane coating is disposed over a tip of the sensor such that the membrane coating is disposed over the working electrode; a capping membrane is embedded with analyte, the capping membrane disposed over at least a portion of the tip of the sensor; the membrane coating comprises an analyte limiting barrier is disposed over the tip of the sensor; the capping membrane is disposed over at least a portion of the membrane coating and is embedded with analyte, the capping membrane comprising a P4VP-co-
  • a method for estimating a thickness of a membrane coating on an in vivo sensor comprising: providing a sensor having a tip, the tip comprising a working electrode configured to detect a plurality of signals over a period of time, a membrane coating disposed over the tip, and a capping membrane having analyte embedded therein, wherein the capping membrane is disposed over at least a portion of the tip; detecting, by a working electrode, a plurality of signals over a period of time; determining current measurements from the plurality of signals; and estimating a thickness of the membrane coating at least in part by analyzing a relationship of the current measurements to the period of time.
  • Clause 45 The method of any one of clauses 43-44, wherein the analyte limiting barrier comprises a glucose limiting barrier.
  • Clause 46 The method of any one of clauses 43-45, wherein the analyte comprises: glucose; ketone, or lactate.
  • Clause 47 The method of any one of clauses 43-46, wherein a permeability measurement of the capping membrane is higher than a permeability measurement of the membrane coating.
  • Clause 48 The method of any one of clauses 43-47, wherein the capping membrane comprises a P4VP-co-PSS membrane.
  • Clause 50 The method of any one of clauses 43-49, wherein analyzing the relationship of the current measurements to the period of time comprises: integrating the current measurements over the period of time; and identifying a local maximum current over the period of time.
  • Clause 51 The method of any one of clauses 43-50, further comprising: detecting, by the working electrode, a second plurality of signals over a second period of time; determining a second current measurement from the second plurality of signals; determining a third current measurement by subtracting the second current measurement from the first current measurement; and estimating a thickness of the membrane coating based at least in part on the third current measurement, wherein the second time period is after the first time period.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Physics & Mathematics (AREA)
  • Molecular Biology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pathology (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Medical Informatics (AREA)
  • Optics & Photonics (AREA)
  • Surgery (AREA)
  • Biophysics (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Emergency Medicine (AREA)
  • Measurement Of The Respiration, Hearing Ability, Form, And Blood Characteristics Of Living Organisms (AREA)

Abstract

Un capteur, un système et un procédé d'estimation d'épaisseur de membrane par mesure de courant sont proposés. Le procédé consiste à fournir un capteur possédant une électrode de travail et à revêtir une pointe du capteur avec un revêtement de membrane de sorte que le revêtement de membrane est disposé sur l'électrode de travail. Le procédé consiste également à incorporer un analyte dans une membrane de recouvrement et à disposer la membrane de recouvrement sur au moins une partie de la pointe du capteur. Le procédé consiste en outre à détecter, par l'électrode de travail, une pluralité de signaux sur une période, à déterminer des mesures de courant à partir de la pluralité de signaux et à estimer une épaisseur du revêtement de membrane au moins en partie par analyse d'une relation des mesures de courant à la période.
PCT/US2024/052484 2023-10-24 2024-10-23 Systèmes et procédés d'estimation d'épaisseur de membrane par mesure électrochimique Pending WO2025090556A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US202363592605P 2023-10-24 2023-10-24
US63/592,605 2023-10-24

Publications (1)

Publication Number Publication Date
WO2025090556A1 true WO2025090556A1 (fr) 2025-05-01

Family

ID=93432192

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2024/052484 Pending WO2025090556A1 (fr) 2023-10-24 2024-10-23 Systèmes et procédés d'estimation d'épaisseur de membrane par mesure électrochimique

Country Status (1)

Country Link
WO (1) WO2025090556A1 (fr)

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20080039702A1 (en) 2006-08-09 2008-02-14 Abbott Diabetes Care, Inc. Method and System for Providing Calibration of an Analyte Sensor in an Analyte Monitoring System
WO2010099507A1 (fr) 2009-02-26 2010-09-02 Abbott Diabetes Care Inc. Capteurs d'analyte améliorés et procédés de fabrication et d'utilisation de ceux-ci
US8761857B2 (en) 2004-02-09 2014-06-24 Abbott Diabetes Care Inc. Analyte sensor, and associated system and method employing a catalytic agent
US20190274598A1 (en) 2017-08-18 2019-09-12 Abbott Diabetes Care Inc. Systems, devices, and methods related to the individualized calibration and/or manufacturing of medical devices
US20220192553A1 (en) * 2020-12-23 2022-06-23 Abbott Diabetes Care Inc. Analyte sensors for sensing glutamate and methods of using the same
US20230053254A1 (en) * 2021-08-13 2023-02-16 Medtronic Minimed, Inc. Dry electrochemical impedance spectroscopy metrology for conductive chemical layers
WO2023076157A1 (fr) 2021-10-29 2023-05-04 Abbott Diabetes Care Inc. Systèmes, dispositifs et méthodes de surveillance d'analyte

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8761857B2 (en) 2004-02-09 2014-06-24 Abbott Diabetes Care Inc. Analyte sensor, and associated system and method employing a catalytic agent
US20080039702A1 (en) 2006-08-09 2008-02-14 Abbott Diabetes Care, Inc. Method and System for Providing Calibration of an Analyte Sensor in an Analyte Monitoring System
US20190254575A1 (en) 2006-08-09 2019-08-22 Abbott Diabetes Care Inc. Method and System for Providing Calibration of an Analyte Sensor in an Analyte Monitoring System
WO2010099507A1 (fr) 2009-02-26 2010-09-02 Abbott Diabetes Care Inc. Capteurs d'analyte améliorés et procédés de fabrication et d'utilisation de ceux-ci
US20100230285A1 (en) 2009-02-26 2010-09-16 Abbott Diabetes Care Inc. Analyte Sensors and Methods of Making and Using the Same
US20190274598A1 (en) 2017-08-18 2019-09-12 Abbott Diabetes Care Inc. Systems, devices, and methods related to the individualized calibration and/or manufacturing of medical devices
US20220192553A1 (en) * 2020-12-23 2022-06-23 Abbott Diabetes Care Inc. Analyte sensors for sensing glutamate and methods of using the same
US20230053254A1 (en) * 2021-08-13 2023-02-16 Medtronic Minimed, Inc. Dry electrochemical impedance spectroscopy metrology for conductive chemical layers
WO2023076157A1 (fr) 2021-10-29 2023-05-04 Abbott Diabetes Care Inc. Systèmes, dispositifs et méthodes de surveillance d'analyte

Similar Documents

Publication Publication Date Title
US12279867B2 (en) Systems, devices, and methods related to the individualized calibration and/or manufacturing of medical devices
US12350042B2 (en) Continuous analyte measurement systems and systems and methods for implanting them
US11737692B2 (en) Implantable sensor devices, systems, and methods
JP7590439B2 (ja) 複数被検物質を検出するためのセンサアレイシステムおよび方法
JP7542311B2 (ja) 軟質検体センサ
CN107961016B (zh) 具有包括小型感测斑点的感测表面的分析物传感器
US20160183854A1 (en) Analyte monitoring systems, devices, and methods
US20110073475A1 (en) Analyte Sensor
US20140054171A1 (en) Analyte Sensor Utilizing Oxygen as Oxidant
EP3449006A1 (fr) Empilement de chimie in situ pour capteurs de glucose continus
CN112438704B (zh) 生理参数监测仪的校准系统
WO2025090556A1 (fr) Systèmes et procédés d'estimation d'épaisseur de membrane par mesure électrochimique

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 24802390

Country of ref document: EP

Kind code of ref document: A1