ANALYTE SENSOR APPARATUSES HAVING IMPROVED ELECTRODE CONFIGURATIONS AND METHODS FOR MAKING AND USING THEM

• US 20100025238A1
• Filed: 07/31/2008
• Published: 02/04/2010
• Est. Priority Date: 07/31/2008
• Status: Abandoned Application

• Current Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Inventors: Wolfe, Katherine T., Veljella, Ratnakar, Jin, Enjoo, Shah, Rajiv, Soundararajan, Gopikrishnan, Gottlieb, Rebecca K., Mastrototaro, John J., Cooper, Kenneth W., Kannard, Brian T.
• Application Number:
  US12/184,046
• Publication Number:
  US 20100025238A1
• Time in Patent Office: Days
• US Class Current: 204/401
• 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 5/6848 Needles
• CPC Class Codes: A61B 5/6849 in combination with a needle set

Abstract

Embodiments of the invention provide analyte sensors having optimized elements and/or configurations of elements as well as methods for making and using such sensors. Typical embodiments of the invention include glucose sensors used in the management of diabetes.

Claims

1. An analyte sensor apparatus for implantation within a mammal, the analyte sensor apparatus comprising:

an elongated base layer;

a conductive layer disposed on the base layer and comprising a reference electrode, a working electrode and a counter electrode;

an analyte sensing layer disposed on the conductive layer;

an analyte modulating layer disposed on the analyte sensing layer, wherein the analyte modulating layer comprises a composition that modulates the diffusion of an analyte diffusing through the analyte modulating layer; and

a cover layer disposed on the analyte sensor apparatus, wherein the cover layer comprises an aperture positioned on the cover layer so as to facilitate;

an analyte present in the mammal contacting and diffusing through the analyte modulating layer; and

contacting the analyte sensing layer.

2. The analyte sensor apparatus of claim 1, wherein the apparatus comprises a plurality of working electrodes, counter electrodes and reference electrodes.

3. The analyte sensor of claim 2, wherein the plurality of working, counter and reference electrodes are grouped together as a unit and positionally distributed on the conductive layer in a repeating pattern of units.

4. The analyte sensor of claim 3, wherein:

the elongated base layer is made from a material that allows the sensor to twist and bend while implanted in vivo; and

the electrodes are grouped in a configuration that facilitates an in vivo fluid contacting at least one of working electrode as the sensor apparatus twists and bends when the sensor is implanted in vivo.

5. The analyte sensor of claim 3, wherein the electrodes are grouped in a repeating pattern of units that allows the sensor to continue to function if a portion of the sensor having one or more electrodes is dislodged from an in vivo environment and exposed to an ex vivo environment.

6. The analyte sensor of claim 3, wherein the electrodes are grouped in the unit so that a first electrode is disposed in a region proximal to a first edge of the elongated base layer;

a second electrode is disposed in a region proximal to an opposite edge of the elongated base layer; and

a third is disposed in a region of the elongated base layer that is between the first electrode and the second electrode.

7. The analyte sensor apparatus of claim 1, wherein the aperture is positioned on the cover layer proximal to the reference electrode so that a fluid comprising the analyte contacts the reference electrode first;

or

the aperture is positioned on the cover layer so that a fluid comprising the analyte contacts the reference electrode, the working electrode and the counter electrode in a sequential manner.

8. The analyte sensor apparatus of claim 1, wherein the aperture is positioned on the cover layer directly over the reference electrode, the working electrode and the counter electrode.

9. The analyte sensor apparatus of claim 1, wherein the analyte sensing layer comprises an oxidoreductase that generates hydrogen peroxide upon exposure to a ligand for the oxidoreductase, wherein the amount of hydrogen peroxide generated by the polypeptide is proportional to the amount of ligand exposed to the polypeptide.

10. The analyte sensor of claim 1, wherein a pulsed voltage is used to obtain a signal from an electrode.

11. The analyte sensor apparatus of claim 1, wherein the sensor comprises a plurality of reference electrodes, working electrodes or counter electrodes disposed near the aperture in a repetitive configuration that inhibits shadowing of one or more electrodes in the repetitive configuration.

12. The analyte sensor apparatus of claim 1, wherein the sensor is operatively coupled to:

a sensor input capable of receiving a signal from the sensor that is based on a sensed physiological characteristic value in the mammal; and

a processor coupled to the sensor input, wherein the processor is capable of characterizing one or more signals received from the sensor.

13. The analyte sensor apparatus of claim 12, wherein:

the sensor comprises three working electrodes, one counter electrode and one reference electrode;

at least one working electrode is coated with an analyte sensing layer comprising glucose oxidase;

at least one working electrode is not coated with an analyte sensing layer comprising glucose oxidase.

14. The analyte sensor apparatus of claim 13, wherein the processor is capable of characterizing a plurality of signals received from the sensor by:

(a) comparing a first signal received from a working electrode coated with glucose oxidase with a second signal received from a working electrode not coated with glucose oxidase so as to obtain information on a background signal that is not based on a sensed physiological characteristic value in the mammal, wherein the sensed characteristic value is glucose concentration;

or

(b) comparing a first signal received from a working electrode coated with glucose oxidase with a second signal received from a working electrode not coated with glucose oxidase so as to obtain information on a signal generated by an interfering compound.

15. The analyte sensor of claim 14, wherein the interfering compound is acetaminophen, ascorbic acid, bilirubin, cholesterol, creatinine, dopamine, ephedrine, ibuprofen, L-dopa, methyldopa, salicylate, tetracycline, tolazamide, tolbutamide, triglycerides or uric acid.

16. The analyte sensor apparatus of claim 13, wherein two working electrodes are coated with glucose oxidase and the processor is capable of obtaining information on glucose concentrations in the mammal by comparing the signals received from the two working electrodes coated with glucose oxidase.

17. The analyte sensor apparatus of claim 1, wherein at least one electrode is formed from a flexible electrically conductive wire.

18. The analyte sensor apparatus of claim 17, wherein the flexible electrically conductive wire is disposed in the apparatus in a coiled configuration.

19. The analyte sensor apparatus of claim 17, wherein the cover layer comprises a plurality of apertures and is formed from a sheath made from a biocompatible polymeric material.

20. The analyte sensor apparatus of claim 17, wherein the analyte modulating layer is coated over at least 75% of the surface of the electrically conductive wire

21. The analyte sensor apparatus of claim 1, wherein the analyte sensing layer comprises an oxidoreductase polypeptide crosslinked to a carrier polypeptide by a crosslinking compound having the formula:

L₁-CH₂—

(CH₂—

O—

CH₂)_n—

CH₂-L₂

wherein L₁ and L₂ comprise N-Hydroxysuccinimide or pentafluorophenyl moieties and n is equal to 5, 6, 7, 8, 9 or 10.

22. The analyte sensor apparatus of claim 21, wherein L₁ and L₂ comprise N-Hydroxysuccinimide moieties that covalently bond to amine moieties on the oxidoreductase polypeptide and the carrier polypeptide.

23. The analyte sensor apparatus of claim 21, wherein the oxidoreductase polypeptide comprises an enzyme selected from the group consisting of glucose oxidase, glucose dehydrogenase, lactate oxidase, hexokinase and lactose dehydrogenase.

24. The analyte sensor of claim 21, wherein n is equal to 5.

25. The analyte sensor apparatus of claim 21, wherein the crosslinking compound is bis N-succinimidyl-[pentaethylene glycol]ester comprising polyethylene glycol moieties so as to make the analyte sensing layer with more flexible and hydrophilic than a crosslinking compound that does not contain polyethylene glycol moieties.

26. The analyte sensor apparatus of claim 1, wherein a barrier element is disposed on the apparatus so as to inhibit spreading of a layer disposed on an electrode.

27. The analyte sensor apparatus of claim 26, wherein the barrier element is disposed on the apparatus so as to encircle a reactive surface on an electrode.

28. The analyte sensor apparatus of claim 1, wherein the elongated base layer is constructed from a dielectric ceramic material.

29. The analyte sensor apparatus of claim 28, wherein the elongated base layer is at least 100 microns thick.

30. The analyte sensor apparatus of claim 1, wherein an electrode of the apparatus comprises a platinum composition and the apparatus further comprises a titanium composition disposed between the elongated base layer and the conductive layer.

31. The analyte sensor apparatus of claim 1, wherein the apparatus further comprises a gold composition disposed between the titanium composition and the conductive layer.

32. The analyte sensor apparatus of claim 1, further comprising a coating of a Prussian blue composition at a location and in an amount sufficient to mediate an electrical potential of an electrode of the apparatus.

33. The analyte sensor apparatus of claim 1, further comprising an interference rejection layer.

34. The analyte sensor apparatus of claim 33, wherein the interference rejection layer comprises a NAFION composition.

35. The analyte sensor apparatus of claim 1, further comprising an adhesion promoting layer disposed between the analyte sensing layer and the analyte modulating layer.

36. The analyte sensor apparatus of claim 35, wherein a first compound in the adhesion promoting layer is crosslinked to a second compound in the analyte sensing layer.

37. The analyte sensor apparatus of claim 35, wherein the analyte modulating layer is at least 6, 7, 8, 9, 10 or 11 microns thick.

38. The analyte sensor apparatus of claim 1, wherein an electrode exhibits a rounded edge structure.

39. The analyte sensor apparatus of claim 1, further comprising a fuse element that can be triggered after a predetermined period of time or event so as to interrupt a flow of electrical current within the apparatus.

40. The analyte sensor apparatus of claim 12, wherein the processor is capable of comparing a first signal received from a working electrode in response to a first working potential with a second signal received from a working electrode in response to a second working potential, wherein the comparison of the first and second signals at the first and second working potentials can be used to identify a signal generated by an interfering compound.

41. The analyte sensor of claim 40, wherein a working electrode is coated with glucose oxidase and the interfering compound is acetaminophen, ascorbic acid, bilirubin, cholesterol, creatinine, dopamine, ephedrine, ibuprofen, L-dopa, methyldopa, salicylate, tetracycline, tolazamide, tolbutamide, triglycerides or uric acid.

42. The analyte sensor of claim 41, wherein a pulsed voltage is used to obtain a signal from a working electrode.

43. The analyte sensor apparatus of claim 12, wherein the processor is capable of comparing a first signal received from a working electrode coated with glucose oxidase in response to a first working potential with a second signal received from a working electrode coated with glucose oxidase in response to a second working potential, wherein the comparison of the first and second signals at the first and second working potentials can be used to characterize a blood glucose concentration within at least one discreet concentration range.

44. The analyte sensor apparatus of claim 43, wherein the comparison of the first and second signals at the first and second working potentials can be used to characterize a blood glucose concentration within a concentration below 70 mg/dL or above 125 mg/dL.

45. The analyte sensor apparatus of claim 44, wherein at least one working potential is 280, 535 or 635 millivolts.

46. The analyte sensor of claim 1, further comprising a discharge circuit element.

47. The analyte sensor of claim 46, wherein the discharge circuit element is a switch.

48. The analyte sensor of claim 46, further comprising a potentiostat operatively coupled to the sensor to facilitate an electrical discharge from the sensor.

53. The analyte sensor of claim 1, further comprising a processor that detects whether a sensor is sufficiently hydrated for analyte detection by calculating an impedance value;

and comparing the impedance value against a threshold to determine if the sensor is sufficiently hydrated for analyte detection.

54. The analyte sensor of claim 53, further comprising a discharge circuit element.

55. The analyte sensor of claim 53, wherein a pulsed voltage is used to obtain a signal from a working electrode.

49. A method of detecting whether a sensor is sufficiently hydrated for analyte detection, comprising calculating an open circuit potential value between at least two electrodes of the sensor;

and comparing the open circuit potential value against a threshold to determine if the sensor sufficiently hydrated for analyte detection.

50. The method of claim 49, wherein the open circuit potential value is the impedance value.

51. The method of claim 50, further comprising comparing the impedance value against an another threshold to determine if the sensor sufficiently hydrated for analyte detection.

52. The method of claim 49, wherein the impedance value is an approximation of a sum of polarization resistance and/or solution resistance.