OXYGEN-EFFECT FREE ANALYTE SENSOR

• US 20090099434A1
• Filed: 07/14/2008
• Published: 04/16/2009
• Est. Priority Date: 11/15/1999
• Status: Active Grant

• Current Assignee: Abbott Diabetes Care Incorporated (Abbott Laboratories Incorporated)
• Original Assignee: Abbott Diabetes Care Incorporated (Abbott Laboratories Incorporated)
• Inventors: Goti, Yohannes, Heller, Adam, Cho, Hyun, Feldman, Benjamin J., Mao, Fei, Liu, Zenghe, Ouyang, Tianmei
• Granted Patent: US 8,268,143 B2
• Time in Patent Office: Days
• US Class Current: 600/347
• CPC Class Codes: A61B 2560/0223 of calibration, e.g. protocols for calibrating sensors
• CPC Class Codes: A61B 2560/0252 using ambient temperature
• CPC Class Codes: A61B 2560/0276 Determining malfunction
• CPC Class Codes: A61B 5/002 Monitoring the patient using a local or closed circuit, e.g. in a room or building A61B5/0017 takes precedence
• 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 5/4839 combined with drug delivery
• CPC Class Codes: A61M 2205/3576 with non implanted data transmission devices, e.g. using external transmitter or receiver
• CPC Class Codes: A61M 2205/3584 using modem, internet or bluetooth
• CPC Class Codes: A61M 2205/505 Touch-screens; Virtual keyboard or keypads; Virtual buttons; Soft keys; Mouse touches
• CPC Class Codes: A61M 2230/201 Glucose concentration
• CPC Class Codes: A61M 5/1723 using feedback of body parameters, e.g. blood-sugar, pressure measurement of body parameters A61B5/00
• CPC Class Codes: C12Q 1/004 mediator-assisted
• CPC Class Codes: C12Q 1/32 involving dehydrogenase

Abstract

The present invention provides an electrochemical sensor having a sensing chemistry that operates substantially free of any “oxygen effect”. The electrochemical sensors are useful in determining the level of an analyte in a biological sample from a subject. The present invention also provides sensor assemblies including the electrochemical sensors as well as methods of using the same.

Claims

1. An electrochemical sensor, comprising:

at least one substrate comprising a working electrode and a counter electrode;

an dehydrogenase disposed on the working electrode, wherein the dehydrogenase reacts with an analyte of interest resulting in generation of free electrons; and

a redox mediator disposed proximate to the working electrode that assists in the transfer of the free electrons to the working electrode, wherein the redox mediator comprises a transition metal complex having the following formula;

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

3. The sensor of claim 1, wherein the dehydrogenase is glucose dehydrogenase.

4. The sensor of claim 1, wherein glucose dehydrogenase is associated with a co-factor.

5. The sensor of claim 3, wherein the co-factor is flavin adenine dinucleotide (FAD), nicotinamide adenine dinucleotide (NAD), or pyrroloquinoline quinone (PQQ).

6. The sensor of claim 1, wherein the dehydrogenase comprises a complex of glucose dehydrogenase (GDH) and flavin adenine dinucleotide (FAD).

7. The sensor of claim 1, wherein the substrate further comprises a reference electrode.

8. The sensor of claim 1, further comprising a polymeric membrane on the electrode.

9. The sensor of claim 1, wherein the redox mediator further comprises a polymeric backbone and a cross-linker.

10. The sensor of claim 1, wherein the transition metal complex comprises the following formula:

11. The sensor of claim 10, wherein at least one of R₁, R₂, and R′

₁ comprises a reactive group selected from the group consisting of carboxy, activated ester, sulfonyl halide, sulfonate ester, isocyanate, isothiocyanate, epoxide, aziridine, halide, aldehyde, ketone, amine, acrylamide, thiol, acyl azide, acyl halide, hydrazine, hydroxyamine, alkyl halide, imidazole, pyridine, phenol, alkyl sulfonate, halotriazine, imido ester, maleimide, hydrazide, hydroxy, and photo-reactive azido aryl groups.

12. The sensor of claim 11, wherein at least one of R₁, R₂, and R′

₁ is coupled to a polymeric backbone.

13. The sensor of claim 9, wherein the polymeric backbone comprises a poly(vinylpyridine) having the following general structure, where n may be 2, n′

is 17, and n″

is 1;

14. The sensor of claim 9, wherein the cross-linker is polyethylene glycol diglycidyl ether (PEGDGE) having the following general formula:

15. The sensor of claim 9, wherein the redox mediator has the following structure:

16. The sensor of claim 9, wherein the polymeric backbone comprises a poly(vinylpyridine-co-styrene) copolymer.

17. The sensor of claim 9, wherein the cross-linker is triglycidyl glycerol.

18. The sensor of claim 16, wherein the poly(vinylpyridine-co-styrene) copolymer is derivatized by the addition of propylsulfonate and poly(ethyleneoxide) moieties.

19. The sensor of claim 16, wherein the poly(vinylpyridine-co-styrene) copolymer has the following structure:

20. The sensor of claim 16, wherein the polymeric backbone comprises:

a cross-linker; and

a copolymer having the following general structure;

21. An analyte sensor assembly, comprising:

an electrochemical sensor comprising;

at least one substrate comprising a working electrode and a counter electrode,

a working electrode comprising a dehydrogenase disposed thereon, wherein the dehydrogenase reacts with an analyte of interest resulting in generation of free electrons; and

a redox mediator disposed proximate to the working electrode that assists in the transfer of the free electrons to the working electrode, wherein the redox mediator comprises a transition metal complex having the following formula;

22. The analyte sensor assembly of claim 21, wherein at least a portion of the sensor is adapted to be subcutaneously positioned in the subject.

23. The analyte sensor assembly of claim 21, wherein the dehydrogenase is glucose dehydrogenase.

24. The analyte sensor assembly of claim 21, wherein glucose dehydrogenase is associated with a co-factor.

25. The analyte sensor assembly of claim 23, wherein the co-factor is flavin adenine dinucleotide (FAD), nicotinamide adenine dinucleotide (NAD), or pyrroloquinoline quinone (PQQ).

26. The analyte sensor assembly of claim 21, wherein the dehydrogenase comprises a complex of glucose dehydrogenase (GDH) and flavin adenine dinucleotide (FAD).

27. The analyte sensor assembly of claim 21, wherein the substrate further comprises a reference electrode.

28. The analyte sensor assembly of claim 21, further comprising a polymeric membrane on the electrode.

29. The sensor of claim 21, wherein the redox mediator further comprises a polymeric backbone and a cross-linker.

30. The sensor of claim 21, wherein the transition metal complex comprises the following formula:

31. The sensor of claim 30, wherein at least one of R₁, R₂, and R′

₁ comprises a reactive group selected from the group consisting of carboxy, activated ester, sulfonyl halide, sulfonate ester, isocyanate, isothiocyanate, epoxide, aziridine, halide, aldehyde, ketone, amine, acrylamide, thiol, acyl azide, acyl halide, hydrazine, hydroxyamine, alkyl halide, imidazole, pyridine, phenol, alkyl sulfonate, halotriazine, imido ester, maleimide, hydrazide, hydroxy, and photo-reactive azido aryl groups.

32. The sensor of claim 31, wherein at least one of R₁, R₂, and R′

₁ is coupled to a polymeric backbone.

33. The sensor of claim 29, wherein the polymeric backbone comprises a poly(vinylpyridine) having the following general structure, where n may be 2, n′

is 17, and n″

is 1;

34. The sensor of claim 29, wherein the cross-linker is polyethylene glycol diglycidyl ether (PEGDGE) having the following general formula:

35. The sensor of claim 29, wherein the redox mediator has the following structure:

36. The sensor of claim 29, wherein the polymeric backbone comprises a poly(vinylpyridine-co-styrene) copolymer.

37. The sensor of claim 29, wherein the cross-linker is triglycidyl glycerol.

38. The sensor of claim 36, wherein the poly(vinylpyridine-co-styrene) copolymer is derivatized by the addition of propylsulfonate and poly(ethyleneoxide) moieties.

39. The sensor of claim 36, wherein the poly(vinylpyridine-co-styrene) copolymer has the following structure:

40. The sensor of claim 36, wherein the polymeric backbone comprises:

a cross-linker; and

a copolymer having the following general structure;

41. A method for monitoring a level of an analyte using the analyte monitoring system of claim 21, 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.

42. The method of claim 41, wherein the analyte is glucose.

43. The method of claim 41, wherein collecting data comprises generating signals from the sensor and processing the signals into data.

44. The method of claim 41, wherein the data comprises the signals from the sensor.

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

46. The method of claim 41, further comprising administering a drug in response to the data.

47. The method of claim 46, wherein the drug is insulin.

48. The method of claim 47, further comprising obtaining a calibration value from a calibration device to calibrate the data.

49. The method of claim 48, wherein the calibration device is coupled to the display unit.

50. The method of claim 49, further comprising transmitting the calibration value from a transmitter in the display unit to a receiver in the sensor control unit.