Biosensor and methods of use thereof

• US 6,816,742 B2
• Filed: 02/13/2004
• Issued: 11/09/2004
• Est. Priority Date: 03/13/1998
• Status: Expired due to Term

• Current Assignee: LifeScan IP Holdings, LLC
• Original Assignee: Cygnus, Inc. (Johnson & Johnson)
• Inventors: Tamada, Janet, Berner, Bret, Potts, Russell O., Tierney, Michael J., Parris, Norman A., Kim, Lynn
• Primary Examiner(s): Nasser, Robert L.
• Application Number:
  US10/778,721
• Publication Number:
  US 20040167383A1
• Time in Patent Office: 270 Days
• Field of Search: 600/345-350, 600/365, 435/14, 435/808, 435/286.6, 435/25, 436/8, 436/17, 436/149-151, 702/19, 702/22, 702/23, 73/10.1, 73/10.2, 422/6.1, 422/68.1, 422/63, 422/67, 422/82.01, 422/82.03, 204/400, 204/403
• 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 sampling system for monitoring the concentration of an analyte present in a subject, said sampling system comprising:

a sensing device comprising a collection reservoir comprising an enzyme capable of reacting with the analyte to produce hydrogen peroxide and 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, and

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

2. The sampling system of claim 1, wherein the sensor element comprises a platinum-group metal-containing electrode.

3. The sampling system of claim 2, wherein the platinum-group metal is platinum.

4. The sampling system of claim 3, wherein the electrode comprises about 3-7% by weight of platinum dispersed in a polymer matrix.

5. The sampling system of claim 1, wherein the sensor element includes a sensing electrode, a counter electrode, and a reference electrode.

6. The sampling system of claim 1, wherein the sampling system uses a minimally invasive or non-invasive sampling technique selected from the group consisting of sonophoresis, iontophoresis, suction, electroporation, thermal poration, passive diffusion, microfine lances or cannulas, and laser poration.

7. The sampling system of claim 1, wherein the analyte is glucose, and the enzyme is glucose oxidase.

8. The sampling system of claim 1, wherein the electrode has a geometric area of about 1 cm², a background current of about 20 nA, and a sensitivity of about 60 nA/μ

M of hydrogen peroxide.

9. The sampling system of claim 1, wherein the electrode is printed onto a rigid or flexible substrate.

10. The sampling system of claim 1, wherein the sampling system uses a minimally invasive sampling technique of subcutaneous implants or insertions.

11. The sampling system of claim 1, wherein the sampling system uses an invasive sampling technique selected from the group consisting of needle sampling, syringe sampling, and vacuum sampling.

12. The sampling system of claim 1, wherein the collection reservoir further comprises a reservoir selected from the group is selected from the group consisting of a hydrogel, tube, vial, capillary collection device, cannula, and miniaturized flow paths.

13. The sampling system of claim 12, wherein said reservoir comprises a miniaturized etched, ablated or molded flow path.

14. The sampling system of claim 1, wherein said one or more microprocessors further comprise programming to correlate a measurement obtained from the detectable signal with the concentration of the analyte in the subject.

15. The sampling system of claim 14, wherein said programming to correlate comprises calibrating the sampling system at a calibration time point wherein the detectable signal obtained from the sampling system at that time point is correlated to a blood analyte concentration at that time point as determined by direct blood testing of the subject.

16. A method for monitoring the concentration of an analyte present in a subject, wherein the sampling system of claim 1 is in operative contact with the subject, said method comprising:

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

detecting the hydrogen peroxide with the sensor element which reacts electrochemically with the hydrogen peroxide to produce a detectable signal;

measuring the detectable signal to provide a measurement; and

correlating the measurement obtained from the detectable signal with a concentration of the analyte in the subject.

17. The method of claim 16, wherein the subject is a mammalian subject.

18. The method of claim 17, wherein the analyte is transdermally extracted.

19. The method of claim 16, wherein the analyte is present in the subject at a concentration ranging from about 0.1 to 200 millimolar (mM).

20. The method of claim 16, wherein the analyte is glucose, and the enzyme is glucose oxidase.

21. The method of claim 16, wherein the sensor element includes a sensing electrode, a counter electrode, and a reference electrode.

22. The method of claim 16, wherein said subject includes skin, and the sampling system uses a minimally invasive or non-invasive sampling technique comprising enhancement of skin permeability by pricking the skin with micro-needles.

23. The method of claim 16, further comprising performing said contacting, detecting, measuring, and correlating, continually or continuously to monitor the concentration of the analyte in the subject.

24. The method of claim 16, wherein said correlating of the measurement obtained from the detectable signal with the concentration of the analyte in the subject comprises calibrating the sampling system at a calibration time point wherein the detectable signal obtained from the sampling system at that time point is correlated to a blood analyte concentration at that time point as determined by direct blood testing of the subject.

25. The method of claim 16, wherein the sampling system uses a minimally invasive or non-invasive sampling technique selected from the group consisting of sonophoresis, iontophoresis, suction, electroporation, thermal poration, passive diffusion, microfine lances or cannulas, and laser poration.

26. The method of claim 16, wherein the sampling system uses a minimally invasive sampling technique of subcutaneous implants or insertions.

27. The method of claim 16, wherein the sampling system uses an invasive sampling technique selected from the group consisting of needle sampling, syringe sampling, and vacuum sampling.

28. The method of claim 16, wherein the collection reservoir further comprises a reservoir selected from the group is selected from the group consisting of a hydrogel, tube, vial, capillary collection device, cannula, and miniaturized flow paths.

29. The method of claim 27, wherein said reservoir comprises a miniaturized etched, ablated or molded flow path.