Implantable electrochemical biosensor system and method

• US 9,907,499 B2
• Filed: 09/15/2010
• Issued: 03/06/2018
• Est. Priority Date: 09/15/2009
• Status: Active Grant

• Current Assignee: Konamite Limited
• Original Assignee: Agamatrix Incorporated (AgaMatrix Holdings LLC d/b/a WaveForm Diabetes)
• Inventors: Iyengar, Sridhar, Harding, Ian
• Primary Examiner(s): JANG, CHRISTIAN YONGKYUN
• Application Number:
  US12/882,761
• Publication Number:
  US 20110062033A1
• Time in Patent Office: 2,729 Days
• Field of Search: 600345, 600347, 600365
• 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 5/1495 Calibrating or testing of in-vivo probes
• CPC Class Codes: A61B 5/7225 Details of analog processing, e.g. isolation amplifier, gain or sensitivity adjustment, filtering, baseline or drift compensation A61B5/30, A61B5/316 take precedence; transformers for specific applications H01F38/00; amplifiers H03F
• CPC Class Codes: C12Q 1/001 Enzyme electrodes
• CPC Class Codes: C12Q 1/006 for glucose

Abstract

Correction for initial variation in thickness of a polymer layer and for changes in the coating thickness that occur after implantation of a biosensor and therefore provides substantial increase in the accuracy and lifetime of implantable sensors is done using a factor derived from the decay of potential.

Claims

1. A method for determination of the thickness of a polymer layer in an implantable biosensor comprising an electrode and the polymer layer, wherein the polymer layer contains an enzyme, said method comprising the steps of:

(a) placing the biosensor in contact with a solution;

(b) applying a potential (V) to the biosensor sufficient to oxidize or reduce a redox active species in the solution and generate a current,

(c) switching off the applied potential and observing subsequent decay of potential to obtain a plurality of V versus time (t) data points, and

(d) determining the slope (k) of a plot of V versus 1/√

t, wherein the slope (k) provides an indication of the thickness of the polymer layer.

2. The method of claim 1, wherein the redox active species is part of a reversible redox couple and the thickness of the polymer layer is proportional to 1/k.

3. The method of claim 1, wherein the redox active species is part of an irreversible redox couple and the thickness of the polymer layer is proportional to 1/√

k.

4. The method of claim 1, wherein the electrode is platinum.

5. The method claim 1, wherein the electrode is gold.

6. The method of claim 1, wherein for a particular determination of analyte the potential is applied to the biosensor for a period of 60 seconds or less.

7. The method of claim 6, wherein the potential is applied to the biosensor for a period of 40 seconds or less.

8. The method of claim 7, wherein the potential is applied to the biosensor for a period of 10 to 30 seconds.

9. The method of any of claim 6, wherein the V versus t data points are collected during a period of time that is 5 seconds or less after switching off of the applied potential.

10. The method of claim 9, wherein the V versus t data points are collected during a period of time that is 2 seconds or less after switching off of the applied potential.

11. A method for determining an analyte in a sample, comprising the steps of

(a) placing a sample to be tested for analyte in contact with a biosensor comprising an electrode and a polymer layer containing an enzyme,

(b) applying a potential (V) to the biosensor sufficient to oxidize or reduce a redox active species and generate a current,

(c) switching off the applied potential and observing subsequent decay of potential (V) to obtain a plurality of V versus time (t) data points,

(d) determining the slope (k) of a plot of V versus 1/√

t,

(e) determining a correction factor for the thickness of the polymer layer from the slope k,

(f) determining an uncorrected measure of analyte in the sample,

(h) correcting the uncorrected measure of analyte using the correction factor to provide a corrected measure of analyte.

12. The method of claim 11, wherein the analyte is glucose and the enzyme is glucose oxidase.

13. The method of claim 12, wherein the electrode is a platinum electrode.

14. The method of claim 12, wherein the electrode is a gold electrode.

15. The method of claim 11, wherein the uncorrected measure of analyte is a current, I_meas, measured during step (b).

16. The method of claim 15, wherein the correction factor is 1/k if the redox active species is part of a reversible redox couple, and 1/√

k if the redox active species is part of an irreversible redox couple.

17. The method of claim 16, wherein the biosensor is implanted in a living individual, including human individuals, thereby bringing the biosensor into contact with the solution.

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

19. The method of claim 18, wherein the electrode is platinum.

20. The method claim 18, wherein the electrode is gold.

21. The method of claim 17, wherein for a particular determination of analyte the potential is applied to the biosensor for a period of 60 seconds or less.

22. The method of claim 21, wherein the V versus t data points are collected during a period of time that is 5 seconds or less after switching off of the applied potential.