Lyotropic Liquid Crystal Coated Analyte Monitoring Device and Methods of Use

• US 20080177164A1
• Filed: 11/30/2007
• Published: 07/24/2008
• Est. Priority Date: 11/30/2006
• Status: Active Grant

• Current Assignee: Abbott Diabetes Care Incorporated (Abbott Laboratories Incorporated)
• Original Assignee: Abbott Diabetes Care Incorporated (Abbott Laboratories Incorporated)
• Inventors: Rowinski, Pawel, Heller, Adam, Feldman, Benjamin
• Granted Patent: US 8,255,034 B2
• Time in Patent Office: Days
• US Class Current: 600/347
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/1468 using chemical or electrochemical methods, e.g. by polarographic means A61B5/1486 takes precedence
• 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: C12Q 1/006 for glucose
• CPC Class Codes: Y10T 29/49117 Conductor or circuit manufacturing

Abstract

The present invention is directed to membranes composed liquid crystals having continuous aqueous channels, such as a lyotropic liquid crystal, including a cubic phase lyotropic liquid crystal, 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 of the present invention demonstrate considerable sensitivity and stability, and a large signal-to-noise ratio, in a variety of conditions.

Claims

1. An electrochemical analyte sensor, comprising:

a working electrode comprising;

a sensing layer in contact with the electrode;

a cubic phase lyotropic liquid crystal membrane associated with the sensing layer, and

a counter or a reference or a counter/reference electrode in electrochemical communication with the working electrode.

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 2, wherein the glucose-responsive enzyme is a wired enzyme.

5. The electrochemical sensor of claim 2, wherein the glucose-responsive enzyme is a glucose-dehydrogenase.

6. The electrochemical sensor of claim 5, wherein the glucose-dehydrogenase is an FAD-dependent glucose dehydrogenase.

7. The electrochemical sensor of claim 5, wherein the glucose-dehydrogenase is glucose oxidase.

8. The electrochemical sensor of claim 3, wherein the redox mediator comprises a ruthenium-containing complex and/or an osmium-containing complex.

9. The electrochemical sensor of claim 1, wherein the cubic phase lyotropic liquid crystal is substantially non-hydrolyzable in the presence of a lipase.

10. The electrochemical sensor of claim 1, wherein the cubic phase lyotropic liquid crystal comprises a compound of the formula:

11. The electrochemical sensor of claim 10, wherein the cubic phase lyotropic liquid crystal comprises Vitamin E acetate.

12. The electrochemical sensor of claim 1, wherein the sensor is adapted so that at least a portion of the sensor is positionable beneath the skin of a user.

13. The electrochemical sensor of claim 1, wherein the sensor comprises an anticlotting agent.

14. The electrochemical sensor of claim 13, wherein the anticlotting agent is heparin.

15. The electrochemical sensor of claim 13, wherein the cubic phase lyotropic liquid crystal comprises the anticlotting agent.

16. The electrochemical sensor of claim 1, wherein the cubic phase lyotropic liquid crystal membrane is adapted to limit the flux of glucose or lactate thereacross.

17. The electrochemical sensor of claim 1, wherein the analyte is glucose.

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

a sensing layer in contact with the electrode, and

a cubic phase lyotropic liquid crystal membrane associated with the sensing layer.

19. The electrode of claim 18, wherein the sensing layer comprises a glucose-responsive enzyme.

20. The electrode of claim 18, wherein the sensing layer of the working electrode comprises a redox mediator.

21. The electrode of claim 20, wherein the redox mediator comprises a complex selected from the group consisting of a ruthenium-containing complex and an osmium-containing complex.

22. The electrode of claim 19, wherein the glucose-responsive enzyme is a wired enzyme.

23. The electrode of claim 19, wherein the glucose-responsive enzyme is a glucose-dehydrogenase.

24. The electrode of claim 23, wherein the glucose-dehydrogenase is an FAD-dependent glucose dehydrogenase.

25. The electrode of claim 23, wherein the glucose-dehydrogenase is glucose oxidase.

26. The electrode of claim 20, wherein the redox mediator comprises a ruthenium-containing complex and/or an osmium-containing complex.

27. The electrode of claim 18, wherein the cubic phase lyotropic liquid crystal is substantially non-hydrolyzable in the presence of a lipase.

28. The electrode of claim 18, wherein the cubic phase lyotropic liquid crystal comprises a compound of the formula:

29. The electrode of claim 28, wherein the cubic phase lyotropic liquid crystal comprises Vitamin E acetate.

30. The electrode of claim 18, wherein the cubic phase lyotropic liquid crystal membrane is adapted to limit the flux of glucose or lactate thereacross.

31. The electrode of claim 18, wherein the cubic phase lyotropic liquid crystal membrane is adapted to limit the flux of glucose or lactate thereacross in vivo.

32. The electrode of claim 18, wherein the sensing layer comprises an anticlotting agent such as heparin.

33. An analyte sensor assembly, comprising:

an electrochemical sensor comprising a substrate comprising at least one working electrode comprising a sensing layer and a cubic phase lyotropic liquid crystal membrane disposed over the sensing layer, at least one counter electrode, and at least one contact pad coupled to each of the working and counter electrodes, the electrochemical sensor being adapted for implantation of a portion of the electrochemical sensor comprising the working and counter electrodes through skin; and

an electrochemical sensor control unit comprising a housing adapted for placement on skin plurality of conductive contacts disposed on the housing and configured for coupling to the contact pads of the electrochemical sensor;

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

34. The analyte sensor of claim 33, wherein the sensing layer of the working electrode comprises a glucose-responsive enzyme.

35. The analyte sensor of claim 33, wherein the sensing layer of the working electrode comprises a redox mediator.

36. The analyte sensor of claim 35, wherein the redox mediator comprises a ruthenium-containing complex and/or an osmium-containing complex.

37. The analyte sensor of claim 34, wherein the glucose-responsive enzyme is a wired enzyme.

38. The analyte sensor of claim 34, wherein the glucose-responsive enzyme is a glucose-dehydrogenase.

39. The analyte sensor of claim 38, wherein the glucose-dehydrogenase is an FAD-dependent glucose dehydrogenase.

40. The analyte sensor of claim 38, wherein the glucose-dehydrogenase is glucose oxidase.

41. The analyte sensor of claim 33, wherein the cubic phase lyotropic liquid crystal is substantially non-hydrolyzable in the presence of a lipase.

42. The analyte sensor of claim 33, wherein the cubic phase lyotropic liquid crystal comprises a compound of the formula:

43. The analyte sensor of claim 33, wherein the cubic phase lyotropic liquid crystal membrane is adapted to limit the flux of glucose or lactate thereacross.

44. The analyte sensor of claim 33, wherein the cubic phase lyotropic liquid crystal membrane is adapted to limit the flux of glucose or lactose thereacross in vivo.

45. The analyte sensor of claim 33, further comprising an anticlotting agent such as heparin.

47. The method of claim 45, wherein the analyte is glucose.

48. The method of claim 45, wherein the cubic phase lyotropic liquid crystal is substantially non-hydrolyzable in the presence of a lipase.

49. The method of claim 45, wherein the cubic phase lyotropic liquid crystal comprises the compound of the formula:

50. The method of claim 45, wherein the sensor comprises an anticlotting agent such as heparin.

51. The method of claim 45, wherein collecting data comprises generating signals from the sensor and processing the signals into data.

52. The method of claim 45, wherein the data comprises the signals from the sensor.

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

54. The method of claim 45, further comprising administering a drug in response to the data.

55. The method of claim 54, wherein the drug is insulin.

56. The method of claim 45, further comprising obtaining a calibration value from a calibration device to calibrate the data.

57. The method of claim 56, wherein the calibration device is coupled to the display unit.

58. The method of claim 57, further comprising transmitting the calibration value from a transmitter in the display unit to a receiver in the sensor control unit.

46. A method for monitoring a level of an analyte using an analyte sensor assembly, comprising:

an electrochemical sensor comprising a substrate comprising at least one working electrode comprising a sensing layer and a cubic phase lyotropic liquid crystal membrane disposed over the sensing layer, at least one counter electrode, and at least one contact pad coupled to each of the working and counter electrodes, the electrochemical sensor being adapted for implantation of a portion of the electrochemical sensor comprising the working and counter electrodes through skin; and

an electrochemical sensor control unit comprising a housing adapted for placement on skin plurality of conductive contacts disposed on the housing and configured for coupling to the contact pads of the electrochemical sensor;

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

the method further 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.

59. A method of fabricating an electrode for use in a biosensor, comprising:

contacting a sensing layer in contact with a conductive material of an electrode with a cubic phase lyotropic liquid crystal membrane to dispose the cubic phase lyotropic liquid crystal membrane over the sensing layer.

60. The method of claim 59, wherein said contacting is by doctor blading.

61. The method of claim 59, wherein the sensing layer of the working electrode comprises a glucose-responsive enzyme.

62. The method of claim 59, wherein the sensing layer of the working electrode comprises a redox mediator.

63. The method of claim 59, wherein the redox mediator comprises a ruthenium-containing complex and/or an osmium-containing complex.

64. The method of claim 61, wherein the glucose-responsive enzyme is a wired enzyme.

65. The method of claim 61, wherein the glucose-responsive enzyme is a glucose-dehydrogenase.

66. The method of claim 62, wherein the glucose-dehydrogenase is an FAD-dependent glucose dehydrogenase.

67. The method of claim 62, wherein the glucose-dehydrogenase is glucose oxidase.

68. The method of claim 59, wherein the cubic phase lyotropic liquid crystal is substantially non-hydrolyzable in the presence of a lipase.

69. The method of claim 59, wherein the cubic phase lyotropic liquid crystal comprises a compound having the formula:

70. The method of claim 59, wherein the sensing layer comprises an anticlotting agent such as heparin.