Biosensor and methods of use thereof

• US 6,999,810 B2
• Filed: 09/08/2004
• Issued: 02/14/2006
• Est. Priority Date: 03/13/1998
• Status: Expired due to Term

• Current Assignee: LifeScan IP Holdings, LLC
• Original Assignee: Animas Technologies LLC (Johnson & Johnson)
• Inventors: Berner, Bret, Potts, Russell O., Tierney, Michael J., Tamada, Janet, Parris, Norman A., Kim, Lynn
• Primary Examiner(s): Nasser, Robert L.
• APPLICATION: US 20050027179A1
• Time in patent office: 524 Days
• Field of Search: 600345-350, 600/365, 204/400, 204/403, 435/14, 435/25, 435/286.6, 435/80, 436/8, 436/17, 436149-151, 702/19, 702 22- 23, 73/10.1, 73/10.2, 42/61, 42/681, 42/63, 42/67, 42/820.1, 42/820.3
• US Class Current: 600/345
• CPC Class Codes: A61B 5/14514 using means for aiding extraction of interstitial fluid, e.g. microneedles or suction
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/1486 using enzyme electrodes, e.g. with immobilised oxidase
• CPC Class Codes: A61B 5/1495 Calibrating or testing of in-vivo probes
• CPC Class Codes: A61N 1/30 Apparatus for iontophoresis, i.e. transfer of media in ionic state by an electromotoric force into the body, or cataphoresis

Abstract

An automated system for continual transdermal extraction of analytes present in a biological system is provided. The system can be used for detecting and/or measuring the concentration of the analyte using an electrochemical biosensor detection means. The system optionally uses reverse iontophoresis to carry out the continual transdermal extraction of the analytes.

Claims

1. A sensor element comprising

a sensing electrode that reacts electrochemically with hydrogen peroxide to provide a detectable signal, the sensing electrode comprising

platinum, graphite, a polymer matrix, and a geometric surface area that ranges from about 0.1 in about 3 cm², wherein the electrode is affixed to a non-conductive surface, has a background current that ranges from about 2 to about 60 nA or less when measured in a buffer solution at an applied potential of 0.6V, and has a sensitivity of at least about 6 to about 180 nA/μ

M of hydrogen peroxide when measured in a buffer solution at an applied potential of 0.6V.

2. The sensor element of claim 1, wherein the sensor element further comprises a counter electrode and a reference electrode.

3. The sensor element of claim 1, wherein the non-conductive surface is a rigid or flexible substrate.

4. The sensor element of claim 1, wherein, for the sensing electrode, the platinum and graphite are dispersed within a polymer matrix.

5. The sensor element of claim 1, wherein the sensing electrode has a surface area of about 0.5 to about 2 cm².

6. The sensor element of claim 1, wherein the sensing electrode has a surface area of about 1 cm².

7. The sensor element of claim 6, wherein the sensing electrode has a background current of about 20 nA or less, and a sensitivity of at least about 60 nA/μ

M of hydrogen peroxide.

8. The sensor element of claim 1, wherein the sensing electrode has a surface area of about 0.1 cm².

9. The sensor element of claim 8, wherein the sensing electrode has a background current of about 2 nA or less and sensitivity of at least about 6 nA/μ

M of hydrogen peroxide.

10. The sensor element of claim 1, wherein the sensing electrode has a surface area about 3 cm², a background current of about 60 nA or less, and sensitivity of at least about 180 nA/μ

M of hydrogen peroxide.

11. The sensor element of claim 1, wherein the polymer matrix is an electrochemically inert binder.

12. The sensor element of claim 11, wherein the binder comprises a polymer or resin binder.

13. The sensor element of claim 12, wherein the binder is a polymer comprising a polymer selected from the group consisting of vinyl, acrylic, epoxy, phenoxy, and polyester polymers.

14. A method for monitoring an amount or concentration of an analyte present in a biological system, the method comprising

contacting the analyte with an enzyme that reacts with the analyte to produce hydrogen peroxide;

detecting the hydrogen peroxide with a sensor element comprising a sensing electrode that reacts electrochemically with hydrogen peroxide to produce a detectable signal, the sensing electrode comprising platinum, graphite, a polymer matrix, and a geometric surface area that ranges from about 0.1 to about 3 cm², wherein the electrode is affixed to a non-conductive surface, has a background current that ranges from about 2 to about 60 nA or less when measured in a buffer solution at an applied potential of 0.6V, and has a sensitivity of at least about 6 to about 180 nA/μ

M of hydrogen peroxide when measured in a buffer solution at an applied potential of 0.6V; and

measuring the detectable signal, wherein the detectable signal is related to analyte amount or concentration in the biological system.

15. The method of claim 14, wherein the biological system is a mammalian subject.

16. The method of claim 15, wherein the analyte is extracted across a skin or mucosal surface.

17. The method of claim 14, wherein the analyte is glucose and the enzyme comprises glucose oxidase.

18. The method of claim 14, wherein the sensor element further comprises a counter electrode and a reference electrode.

19. The method of claim 14, further comprising correlating the measured detectable signal with an amount or concentration of analyte in the biological system.

20. The method of claim 14, wherein the analyte is provided using a sampling technique comprising a sampling technique selected from the group consisting of iontophoresis, sonophoresis, suction, electroporation, thermal poration, passive diffusion, microfine lances, microfine cannulas, and laser.

21. The method of claim 14, wherein the sensing electrode is in operative contact with a collection reservoir.

22. The method of claim 21, wherein the collection reservoir comprises the enzyme.

23. The method of claim 22, wherein the collection reservoir comprises a hydrogel.

24. A sampling system for monitoring the concentration of an analyte present in a subject, said sampling system comprising:

a sensing device comprising (i) a collection reservoir comprising an enzyme capable of reacting with the analyte to produce hydrogen peroxide, and (ii) a sensor element in operative contact with the reservoir, wherein said sensor element reacts electrochemically with the hydrogen peroxide produced in the reservoir to provide a detectable signal, and said sensor element comprises an electrode having a geometric surface area which ranges from about 0.1 to 3 cm², a background current which ranges from about 2 to 60 nA or less when measured in a buffer solution at 0.6V, and a sensitivity which ranges from about 6 to 180 nA/μ

M of hydrogen peroxide when measured in a buffer solution at 0.6V;

one or more microprocessors in operative communication with the sensing device comprising programming to control operation of the sensing device; and

a sampling device comprising microneedles, microfine lances, or microfine cannulas.

25. The sampling system of claim 24, wherein the sensor element includes a sensing electrode, a counter electrode, and a reference electrode.

26. The sampling system of claim 24, wherein the sampling system also employs a sampling technique selected from the group consisting of sonophoresis, iontophoresis, suction, electroporation, thermal poration, passive diffusion, and laser poration.

27. The sampling system of claim 24, wherein the analyte is glucose, and the enzyme comprises glucose oxidase.

28. The sampling system of claim 24, wherein the electrode is printed onto a rigid or flexible substrate.

29. The sampling system of claim 24, wherein the collection reservoir further comprises a reservoir selected from the group consisting of a hydrogel, tube, vial, capillary collection device, cannula, and miniaturized flow paths.

30. The sampling system of claim 29, wherein said reservoir comprises a miniaturized etched, ablated or molded flow path.

31. A sampling system for monitoring the concentration of an analyte present in a subject, said sampling system comprising:

a sensing device comprising

(i) a collection reservoir comprising an enzyme capable of reacting with the analyte to produce hydrogen peroxide, and

(ii) a sensor element in operative contact with the reservoir, wherein said sensor element reacts electrochemically with the hydrogen peroxide produced in the reservoir to provide a detectable signal, the sensing electrode comprising a platinum-group metal, graphite, a polymer matrix, and a geometric surface area that ranges from about 0.1 to about 3 cm², wherein the electrode has a background current that ranges from about 2 to about 60 nA or less when measured in a buffer solution at an applied potential of 0.6V, and has a sensitivity of at least about 6 to about 180 nA/μ

M of hydrogen peroxide when measured in a buffer solution at an applied potential of 0.6V;

one or more microprocessors in operative communication with the sensing device comprising programming to control operation of the sensing device; and

a sampling device comprising microneedles, microfine lances, or microfine cannulas.

32. The sampling system of claim 31, wherein the sensor element includes a sensing electrode, a counter electrode, and a reference electrode.

33. The sampling system of claim 31, wherein the sampling system also employs a sampling technique selected from the group consisting of sonophoresis, iontophoresis, suction, electroporation, thermal poration, passive diffusion, and laser poration.

34. The sampling system of claim 31, wherein the analyte is glucose, and the enzyme comprises glucose oxidase.

35. The sampling system of claim 31, wherein the electrode is printed onto a rigid or flexible substrate.

36. The sampling system of claim 31, wherein the collection reservoir further comnrises a reservoir selected from the group consisting of a hydrogel, tube, vial, capillary collection device, cannula, and miniaturized flow paths.

37. The sampling system of 36, wherein said reservoir comprises a mnuaturized etched, ablated or molded flow path.

38. A sampling system for monitoring the concentration of an analyte present in a subject, said sampling system comprising:

a sensing device comprising

(i) a collection reservoir comprising an enzyme capable of reacting with the analyte to produce hydrogen peroxide, and

(ii) a sensor element in operative contact with the reservoir, wherein said sensor element reacts electrochemically with the hydrogen peroxide produced in the reservoir to provide a detectable signal, the sensing electrode comprising platinum, graphite, a polymer matrix, and a geometric surface area that ranges from about 0.1 to about 3 cm², wherein the electrode has a background current that ranges from about 2 to about 60 nA or less when measured in a buffer solution at an applied potential of 0.6V, and has a sensitivity of at least about 6 to about 180 nA/μ

M of hydrogen peroxide when measured in a buffer solution at an applied potential of 0.6V;

one or more microprocessors in operative communication with the sensing device comprising programming to control operation of the sensing device; and

a sampling device comprising microneedles, microfine lances, or microfine cannulas.

39. The sampling system of claim 38, wherein the sensor element includes a sensing electrode, a counter electrode, and a reference electrode.

40. The sampling system of claim 38, wherein the sampling system also employs a sampling technique selected from the group consisting of sonophoresis, iontophoresis, suction, electroporation, thermal poration, passive diffusion, and laser poration.

41. The sampling system of claim 38, wherein the analyte is glucose, and the enzyme comprises glucose oxidase.

42. The sampling system of claim 38, wherein the electrode is printed onto a rigid or flexible substrate.

43. The sampling system of claim 38, wherein the collection reservoir further comprises a reservoir selected from the group consisting of a hydrogel, tube, vial, capillary collection device, cannula, and miniaturized flow paths.

44. The sampling system of claim 43, wherein said reservoir comprises a miniaturized etched, ablated or molded flow path.