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EP-4397242-B1 - ANALYTE SENSORS WITH A SENSING SURFACE HAVING SMALL SENSING SPOTS

EP4397242B1EP 4397242 B1EP4397242 B1EP 4397242B1EP-4397242-B1

Inventors

  • HOSS, UDO
  • LE, PHU
  • WANG, YI
  • FUJIMOTO, FRANK DAVID
  • QIAN, SUYUE
  • TRAN, LAM

Dates

Publication Date
20260513
Application Date
20111208

Claims (17)

  1. An analyte sensor (500, 700, 800) comprising: a first working electrode (501, 720, 770, 820) and at least one further electrode (503); wherein the first working electrode (501, 720, 770, 820) comprises a sensing surface comprising: a first layer comprising a first array of two or more individual sensing elements (508, 710, 760, 810) disposed on the sensing surface of the first working electrode and disposed laterally to each other; and a second layer comprising a second array of two or more sensing elements, each aligned on top of a corresponding sensing element of the first array of sensing elements; wherein each sensing element comprises an analyte-responsive enzyme; and wherein each sensing element further comprises a polymeric electron transfer agent to transfer electrons between an analyte and the first working electrode.
  2. The analyte sensor of claim 1, wherein the at least one further electrode is a reference electrode, a counter electrode, or a counter/reference electrode.
  3. The analyte sensor of claim 1 or 2, wherein the at least one further electrode is a counter/reference electrode.
  4. The analyte sensor of any one of claims 1-3, wherein the analyte-responsive enzyme in the sensing elements of the first array and the second array are the same.
  5. The analyte sensor of any one of claims 1-4, wherein the analyte-responsive enzyme in the sensing elements of the first array and the second array comprise a glucose-responsive enzyme.
  6. The analyte sensor of any one of claims 1-5, wherein the analyte-responsive enzyme in the sensing elements of the first array and the second array comprise glucose oxidase.
  7. The analyte sensor of any one of claims 1-6, wherein the polymeric electron transfer agent comprises a transition metal compound or complex.
  8. The analyte sensor of any one of claims 1-7, wherein the polymeric electron transfer agent comprises a ruthenium-containing complex or an osmium-containing complex.
  9. The analyte sensor of any one of claims 1-8, wherein the polymeric electron transfer agent comprises one or more ligands covalently bound to a polymer having at least one nitrogen-containing heterocycle such as a pyridine or an imidazole.
  10. The analyte sensor of any one of claims 1-9, wherein the sensing elements of the first layer and the sensing element of the second layer are contiguous.
  11. The analyte sensor of any one of claims 1-10, further comprising a flux limiting membrane that covers the sensing elements.
  12. The analyte sensor of any one of claims 1-11, further comprising a sensor control unit with factory-determined calibration measurements input or stored therein such that no user calibration or recalibration of the analyte sensor is required during use.
  13. The analyte sensor of any one of claims 1-3, wherein the analyte-responsive enzyme comprises a glucose-responsive enzyme.
  14. The analyte sensor of any one of claims 1-3 or 13, wherein the analyte-responsive enzyme comprises glucose oxidase.
  15. The analyte sensor of any one of claims 1-3, 13, or 14, wherein the sensing elements comprise polyethylene glycol.
  16. The analyte sensor of any one of claims 1-3 or 13-15, further comprising a membrane disposed over the sensing elements that limits flux of analyte to the sensing elements.
  17. The analyte sensor of any one of claims 1-3 or 13-16, further comprising a sensor control unit with factory-determined calibration measurements which are (i) input into the sensor control unit using a receiver of the sensor control unit; or (ii) stored in a calibration data storage unit within the sensor control unit.

Description

INTRODUCTION In many instances it is desirable or necessary to regularly monitor the concentration of particular constituents in a fluid. A number of systems are available that analyze the constituents of bodily fluids such as blood, urine and saliva. Examples of such systems conveniently monitor the level of particular medically significant fluid constituents, such as, for example, cholesterol, ketones, vitamins, proteins, and various metabolites or blood sugars, such as glucose. Diagnosis and management of patients suffering from diabetes mellitus, a disorder of the pancreas where insufficient production of insulin prevents normal regulation of blood sugar levels, requires carefully monitoring of blood glucose levels on a daily basis. A number of systems that allow individuals to easily monitor their blood glucose are currently available. Such systems include electrochemical biosensors, including those that comprise a glucose sensor that is adapted for insertion into a subcutaneous site within the body for the continuous monitoring of glucose levels in bodily fluid of the subcutaneous site (see for example, U.S. Patent No. 6,175,752 to Say et al). A person may obtain a blood sample by withdrawing blood from a blood source in his or her body, such as a vein, using a needle and syringe, for example, or by lancing a portion of his or her skin, using a lancing device, for example, to make blood available external to the skin, to obtain the necessary sample volume for in vitro testing. The person may then apply the fresh blood sample to a test strip, whereupon suitable detection methods, such as calorimetric, electrochemical, or photometric detection methods, for example, may be used to determine the person's actual blood glucose level. The foregoing procedure provides a blood glucose concentration for a particular or discrete point in time, and thus, must be repeated periodically, in order to monitor blood glucose over a longer period. In addition to the discrete or periodic, in vitro, blood glucose-monitoring systems described above, at least partially implantable, or in vivo, blood glucose-monitoring systems, which are constructed to provide continuous in vivo measurement of an individual's blood glucose concentration, have been described and developed. Such analyte monitoring devices are constructed to provide for continuous or automatic monitoring of analytes, such as glucose, in the blood stream or interstitial fluid. Such devices include electrochemical sensors, at least a portion of which are operably positioned in a blood vessel or in the subcutaneous tissue of a user. While continuous glucose monitoring is desirable, there are several challenges associated with optimizing manufacture protocols to improve yield and uniformity of the sensing elements of the biosensors constructed for in vivo use. Accordingly, further development of manufacturing techniques and methods, as well as analyte-monitoring devices, systems, or kits employing the same, is desirable. WO 2010/028708 discloses an electrode system for measuring the concentration of an analyte under in-vivo conditions wherein the enzyme layer of the working electrode is provided in the form of multiple fields that are arranged at a distance from each other on the conductor of the working electrode. The enzyme layer can contain metal oxide particles, preferably manganese dioxide particles, as catalytic redox mediator. US 2009/198117 and US 2009/308742 discloses analyte sensors having nanostructured electrodes. US 2008/214916 discloses delivery of a fluid via a device or mechanism that is also capable of in vivo sensing of one or more analytes. US 2005/230270 discloses carbon nanotube nanoelectrode arrays for sensing. US 2005/051427 discloses an electrode array for use in an electrochemical device. Summary of the Invention The claimed invention is set out in the appended claims. Thus, in one aspect, the invention relates to an analyte sensor, comprising:a first working electrode and at least one further electrode; wherein the first working electrode comprises a sensing surface comprising: a first layer comprising a first array of two or more individual sensing elements disposed on the sensing surface of the first working electrode and disposed laterally to each other; anda second layer comprising a second array of two or more sensing elements, each aligned on top of a corresponding sensing element of the first array of sensing elements;wherein each sensing element comprises an analyte-responsive enzyme; andwherein each sensing element further comprises a polymeric electron transfer agent to transfer electrons between an analyte and the first working electrode. It will be appreciated that methods as disclosed herein are not part of the claimed invention. SUMMARY Embodiments of the present disclosure relate to analyte determining methods and devices (e.g., electrochemical analyte monitoring systems) that have a sensing surface that includes two or more