Reference Electrodes Having An Extended Lifetime for Use in Long Term Amperometric Sensors

• US 20090294301A1
• Filed: 06/02/2008
• Published: 12/03/2009
• Est. Priority Date: 06/02/2008
• Status: Active Grant

• Current Assignee: Abbott Diabetes Care Incorporated (Abbott Laboratories)
• Original Assignee: Abbott Diabetes Care Incorporated (Abbott Laboratories)
• Inventors: FELDMAN, BENJAMIN J., OUYANG, TIANMEI, LIU, ZENGHE
• Granted Patent: US 8,155,722 B2
• Time in Patent Office: Days
• US Class Current: 205/775
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/14546 for measuring analytes not otherwise provided for, e.g. ions, cytochromes
• CPC Class Codes: A61B 5/14865 invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors
• CPC Class Codes: A61B 5/1495 Calibrating or testing of in-vivo probes
• CPC Class Codes: C12Q 1/006 for glucose

Abstract

The present application provides Ag/AgCl based reference electrodes having an extended lifetime that are suitable for use in long term amperometric sensors. Electrochemical sensors equipped with reference electrodes described herein demonstrate considerable stability and extended lifetime in a variety of conditions.

Claims

1. A reference electrode for use in electrochemical sensor, comprising:

a layer of Ag/AgCl having a lateral surface and a layer of permselective coating comprising poly(vinylpyridine-co-styrene) disposed over the lateral surface of the layer of Ag/AgCl.

2. The reference electrode of claim 1, wherein the permselective coating comprises poly(2-vinylpyridine-co-styrene).

3. The reference electrode of claim 1, wherein the permselective coating comprises poly(4-vinylpyridine-co-styrene).

4. The reference electrode of claim 1, wherein at least a portion of the reference electrode is adapted to be subcutaneously positioned in a subject.

5. An electrochemical sensor, comprising:

a working electrode comprising a sensing layer in contact with a conductive material of the electrode and a membrane disposed over the sensing layer; and

a reference electrode comprising a layer of Ag/AgCl having a lateral surface and a layer of permselective coating comprising poly(vinylpyridine-co-styrene) disposed over the lateral surface of the layer of Ag/AgCl,

wherein the reference electrode is in electrochemical communication with the working electrode.

6. The electrochemical sensor of claim 5, wherein the permselective coating comprises poly(2-vinylpyridine-co-styrene).

7. The electrochemical sensor of claim 5, wherein the permselective coating comprises poly(4-vinylpyridine-co-styrene).

8. The electrochemical sensor of claim 5, wherein the sensing layer of the working electrode comprises a glucose-responsive enzyme.

9. The electrochemical sensor of claim 5, wherein the sensing layer of the working electrode comprises a redox mediator.

10. The electrochemical sensor of claim 9, wherein the redox mediator comprises a complex selected from the group consisting of a ruthenium-containing complex and an osmium-containing complex.

11. The electrochemical sensor of claim 9, wherein the redox mediator is non-leachable with respect to the working electrode.

12. The electrochemical sensor of claim 9, wherein the redox mediator is immobilized on the working electrode.

13. The electrochemical sensor of claim 5, wherein at least a portion of the electrochemical sensor is adapted to be subcutaneously positioned in a subject.

14. An analyte sensor assembly, comprising:

an electrochemical sensor comprising a flexible substrate comprising

(i) at least one working electrode comprising a sensing layer and a membrane disposed over the sensing layer,

(ii) at least one reference electrode comprising a layer of Ag/AgCl having a lateral surface and a layer of permselective coating comprising poly(vinylpyridine-co-styrene) disposed over the lateral surface of the layer of Ag/AgCl,

(iii) at least one contact pad coupled to each of the working and reference electrodes,

wherein the electrochemical sensor is adapted for implantation of a portion of the electrochemical sensor comprising the working and reference electrodes through skin; and

an electrochemical sensor control unit comprising

(i) a housing adapted for placement on skin;

(ii) a plurality of conductive contacts disposed on the housing and configured for coupling to the contact pads of the electrochemical sensor; and

(iii) an rf transmitter disposed in the housing and coupled to the plurality of conductive contacts for transmitting data obtained using the electrochemical sensor.

15. The analyte sensor assembly of claim 14, wherein the permselective coating comprises poly(2-vinylpyridine-co-styrene).

16. The analyte sensor assembly of claim 14, wherein the permselective coating comprises poly(4-vinylpyridine-co-styrene).

17. The analyte sensor assembly of claim 14, wherein the sensing layer of the working electrode comprises a glucose-responsive enzyme.

18. The analyte sensor assembly of claim 14, wherein the sensing layer of the working electrode comprises a redox mediator.

19. The analyte sensor assembly of claim 14, wherein the redox mediator comprises a complex selected from the group consisting of a ruthenium-containing complex and an osmium-containing complex.

20. The analyte sensor assembly of claim 18, wherein the redox mediator is non-leachable with respect to the working electrode.

21. The analyte sensor assembly of claim 18, wherein the redox mediator is immobilized on the working electrode.

22. The analyte sensor assembly of claim 14, wherein the membrane limits flux of glucose or lactate thereacross.

23. The analyte sensor assembly of claim 14, wherein the membrane limits flux of glucose or lactose thereacross in vivo.

24. A method for monitoring a level of an analyte using the analyte monitoring system of claim 14, the method comprising:

inserting the electrochemical sensor into skin of a patient;

attaching the electrochemical sensor control unit to the skin of the patient;

coupling a plurality of conductive contacts disposed in the sensor control unit to a plurality of contact pads disposed on the sensor;

collecting data, using the sensor control unit, regarding a level of an analyte from signals generated by the sensor;

transmitting the collected data to the display unit using the rf transmitter of the sensor control unit; and

displaying an indication of the level of the analyte on the display of the display unit.

25. The method of claim 24, wherein the analyte is glucose.

26. The method of claim 24, wherein collecting data comprises generating signals from the sensor and processing the signals into data.

27. The method of claim 24, wherein the data comprises the signals from the sensor.

28. The method of claim 24, further comprising activating an alarm if the data indicates an alarm condition.

29. The method of claim 24, further comprising administering a drug in response to the data.

30. The method of claim 29, wherein the drug is insulin.

31. The method of claim 30, further comprising obtaining a calibration value from a calibration device to calibrate the data.

32. The method of claim 31, wherein the calibration device is coupled to the display unit.

33. The method of claim 32, further comprising transmitting the calibration value from a transmitter in the display unit to a receiver in the sensor control unit.