Heterocyclic nitrogen containing polymers coated analyte monitoring device and methods of use

• US 20080179187A1
• Filed: 01/31/2007
• Published: 07/31/2008
• Est. Priority Date: 01/31/2007
• Status: Active Grant

• Current Assignee: Abbott Diabetes Care Incorporated (Abbott Laboratories)
• Original Assignee: Abbott Diabetes Care Incorporated (Abbott Laboratories)
• Inventors: Cho, Hyun, Feldman, Benjamin J., Ouyang, Tianmei
• Granted Patent: US 8,808,515 B2
• Time in Patent Office: Days
• US Class Current: 204/400
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• 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: A61B 5/6849 in combination with a needle set
• CPC Class Codes: A61K 38/28 Insulins
• CPC Class Codes: C12Q 1/001 Enzyme electrodes
• CPC Class Codes: C12Q 1/006 for glucose
• CPC Class Codes: G01N 27/3271 Amperometric enzyme electrodes for analytes in body fluids, e.g. glucose in blood amperometry per se G01N27/49; aspects concerning the enzyme reagent C12Q1/001
• CPC Class Codes: G01N 27/3272 Test elements therefor, i.e. disposable laminated substrates with electrodes, reagent and channels optical biosensors G01N33/52
• CPC Class Codes: G01N 27/3335 the membrane containing at least one organic component G01N27/3271 takes precedence; aspects concerning the enzyme reagent in enzyme electrodes C12Q1/001

Abstract

The present invention is directed to membranes composed of heterocyclic nitrogen groups, such as vinylpyridine and to electrochemical sensors equipped with such membranes. The membranes are useful in limiting the diffusion of an analyte to a working electrode in an electrochemical sensor so that the sensor does not saturate and/or remains linearly responsive over a large range of analyte concentrations. Electrochemical sensors equipped with membranes described herein demonstrate considerable sensitivity and stability, and a large signal-to-noise ratio, in a variety of conditions.

Claims

1. An electrochemical sensor, comprising:

a working electrode comprising;

a sensing layer in contact with a conductive material of the electrode;

a membrane disposed over the sensing layer, wherein the membrane comprises a crosslinker and a polymer having the formula;

2. The electrochemical sensor of claim 1, wherein the sensing layer of the working electrode comprises a glucose-responsive enzyme.

3. The electrochemical sensor of claim 1, wherein the sensing layer of the working electrode comprises a redox mediator.

4. The electrochemical sensor of claim 3, wherein the redox mediator comprises a complex selected from the group consisting of a ruthenium-containing complex and an osmium-containing complex.

5. The electrochemical sensor of claim 3, wherein the redox mediator is non-leachable with respect to the working electrode.

6. The electrochemical sensor of claim 3, wherein the redox mediator is immobilized on the working electrode.

7. The electrochemical sensor of claim 1, wherein the polymer comprises the formula:

8. The electrochemical sensor of claim 1, wherein the crosslinker comprises a poly(ethylene glycol).

9. The electrochemical sensor of claim 8, wherein the poly(ethylene glycol) is a poly(ethylene glycol) diglycidyl ether.

10. The electrochemical sensor of claim 1, wherein the membrane limits flux of glucose or lactate thereacross.

11. The electrochemical sensor of claim 1, wherein the membrane limits flux of glucose or lactose thereacross in vivo.

12. An electrode for use in a biosensor, comprising:

a sensing layer in contact with a conductive material of the electrode, and

a membrane disposed over the sensing layer, wherein the membrane comprises a crosslinker and a polymer having the formula;

13. The electrode of claim 12, wherein the sensing layer of the working electrode comprises a glucose-responsive enzyme.

14. The electrode of claim 12, wherein the sensing layer of the working electrode comprises a redox mediator.

15. The electrode 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.

16. The electrode of claim 14, wherein the redox mediator is non-leachable with respect to the working electrode.

17. The electrode of claim 14, wherein the redox mediator is immobilized on the working electrode.

18. The electrode of claim 12, wherein the polymer comprises the formula:

19. The electrode of claim 12, wherein the crosslinker comprises a poly(ethylene glycol).

20. The electrode of claim 19, wherein the poly(ethylene glycol) is a poly(ethylene glycol) diglycidyl ether.

21. The electrode of claim 12, wherein the membrane limits flux of glucose or lactate thereacross.

22. The electrode of claim 12, wherein the membrane limits flux of glucose or lactose thereacross in vivo.

23. 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, wherein the membrane comprises a crosslinker and a polymer having the formula;

24. The analyte sensor of claim 23, wherein the sensing layer of the working electrode comprises a glucose-responsive enzyme.

25. The analyte sensor of claim 23, wherein the sensing layer of the working electrode comprises a redox mediator.

26. The analyte sensor of claim 25, wherein the redox mediator comprises a complex selected from the group consisting of a ruthenium-containing complex and an osmium-containing complex.

27. The analyte sensor of claim 25, wherein the redox mediator is non-leachable with respect to the working electrode.

28. The analyte sensor of claim 25, wherein the redox mediator is immobilized on the working electrode.

29. The analyte sensor of claim 23, wherein the polymer comprises the formula:

30. The analyte sensor of claim 23, wherein the crosslinker comprises a poly(ethylene glycol).

31. The analyte sensor of claim 30, wherein the poly(ethylene glycol) is a poly(ethylene glycol) diglycidyl ether.

32. The analyte sensor of claim 23, wherein the membrane limits flux of glucose or lactate thereacross.

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

34. A method for monitoring a level of an analyte using the analyte monitoring system of claim 23, 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.

35. The method of claim 34, wherein the analyte is glucose.

36. The method of claim 34, wherein the polymer comprises the formula:

37. The method of claim 34, wherein the crosslinker comprises a poly(ethylene glycol).

38. The method of claim 37, wherein the poly(ethylene glycol) is a poly(ethylene glycol) diglycidyl ether.

39. The method of claim 34, wherein collecting data comprises generating signals from the sensor and processing the signals into data.

40. The method of claim 34, wherein the data comprises the signals from the sensor.

41. The method of claim 34, further comprising activating an alarm if the data indicates an alarm condition.

42. The method of claim 34, further comprising administering a drug in response to the data.

43. The method of claim 42, wherein the drug is insulin.

44. The method of claim 43, further comprising obtaining a calibration value from a calibration device to calibrate the data.

45. The method of claim 44, wherein the calibration device is coupled to the display unit.

46. The method of claim 45, further comprising transmitting the calibration value from a transmitter in the display unit to a receiver in the sensor control unit.

47. A membrane for use in an electrochemical sensor, comprising:

a crosslinker; and

a polymer having the formula;

48. The membrane of claim 47, wherein l is substituted with an aryl, alkoxy, alkenyl, alkynyl, -F, -Cl, -OH, aldehyde, ketone, ester, or amide.

49. The membrane of claim 47, wherein D is styrene or C1-C18 alkyl methacrylate.

50. The membrane of claim 47, wherein the polymer has a formula selected from the group consisting of:

51. The membrane of claim 47, wherein the polymer has a molecular weight of between about 50,000-1,000,000 kD.

52. The membrane of claim 47, wherein the polymer further comprises a B-containing copolymer such that the polymer has the formula:

53. The membrane of claim 52, wherein B is selected from a group consisting of a chelator, a negatively charged constituent, a hydrophobic hydrocarbon constituent, a hydrophilic hydroxyl or polyhydroxy constituent, a silicon polymer, and a poly(ethylene glycol).

54. The membrane of claim 52, wherein B is a poly(ethylene glycol) having a molecular weight of from about 100 to about 20,000 kD.

55. The membrane of claim 52, wherein the polymer has a formula selected from the group consisting of:

56. An electrochemical sensor, comprising:

a working electrode comprising;

a sensing layer in contact with a conductive material of the electrode;

a membrane disposed over the sensing layer, the membrane comprising a crosslinker and a polymer having the formula;

57. The electrochemical sensor of claim 56, wherein l is substituted with an aryl, alkoxy, alkenyl, alkynyl, -F, -Cl, -OH, aldehyde, ketone, ester, or amide.

58. The electrochemical sensor of claim 56, wherein D is styrene or C1-C18 alkyl methacrylate.

59. The electrochemical sensor of claim 56, wherein the polymer has a formula selected from the group consisting of:

60. The electrochemical sensor of claim 56, wherein the polymer has a molecular weight of between about 50,000-1,000,000 kD.