Method and apparatus for assay of electrochemical properties

• US 8,512,546 B2
• Filed: 01/24/2012
• Issued: 08/20/2013
• Est. Priority Date: 08/21/2003
• Status: Active Grant

• Current Assignee: Agamatrix Incorporated (AgaMatrix Holdings LLC d/b/a WaveForm Diabetes)
• Original Assignee: Agamatrix Incorporated (AgaMatrix Holdings LLC d/b/a WaveForm Diabetes)
• Inventors: Iyengar, Sridhar G., Harding, Ian
• Primary Examiner(s): Noguerola, Alex
• Application Number:
  US13/356,827
• Publication Number:
  US 20120205259A1
• Time in Patent Office: 574 Days
• Field of Search: 205/775, 205/777.5, 205/792, 205/789, 20440301-40315, 204416-419, 204/424
• US Class Current: 205/775
• 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: C12Q 1/001 Enzyme electrodes
• CPC Class Codes: C12Q 1/004 mediator-assisted
• CPC Class Codes: C12Q 1/006 for glucose
• CPC Class Codes: G01N 27/26 by investigating electrochemical variables; by using electrolysis or electrophoresis
• CPC Class Codes: G01N 27/3274 Corrective measures, e.g. error detection, compensation for temperature or hematocrit, calibration coding of calibration information G01N33/48771
• CPC Class Codes: G01N 27/4168 Oxidation-reduction potential, e.g. for chlorination of water water analysis G01N33/18

Abstract

The presence of a select analyte such as glucose in the sample is evaluated in an electrochemical system using a conduction cell-type apparatus. A potential or current is generated between the two electrodes of the cell sufficient to bring about oxidation or reduction of the analyte or of a mediator in an analyte-detection redox system, thereby forming a chemical potential gradient of the analyte or mediator between the two electrodes after the gradient is established, the applied potential or current is discontinued and an analyte-independent signal is obtained from the relaxation of the chemical potential gradient. The analyte-independent signal is used to correct the analyte-dependent signal obtained during application of the potential or current.

Claims

1. In a method for electrochemical determination of an analyte in a sample disposed in a conduction cell the improvement comprising the step of applying a correction based on an analyte-independent measurement on the sample to an analyte-dependent measurement on the sample to produce a corrected determination of analyte, wherein the analyte-independent measurement is obtained by observation of potential difference between electrodes of the conduction cell at one or more times after an external potential has first applied to and then removed from conduction cell.

2. The improvement of claim 1, wherein the analyte-independent measurement is the time from the removal of the applied potential for the measured potential to reach a predetermined value.

3. The improvement of claim 1, wherein the analyte-independent measurement is the potential at a predetermined time after the removal of the applied potential.

4. The improvement of claim 1, wherein the analyte-independent measurement is a measure of the rate of decay of the potential after the removal of the applied potential.

5. The improvement of claim 4, wherein the measure of the rate of decay is the slope of a plot of potential versus time during a pre-deter fined time interval after the removal of the applied potential.

6. The improvement of claim 4, wherein the measure of the rate of decay is the slope of a plot of log(potential) versus time during a pre-determined time interval after the removal of the applied potential.

7. The improvement of claim 4, wherein the measure of the rate of decay is the slope of a plot of 1/(potential)² versus time during a pre-determined time interval after the removal of the applied potential.

8. A method of evaluating a sample for the presence of a select analyte comprising the steps of:

(a) introducing the sample into a space between two electrodes of a conduction cell;

(b) applying a potential between the two electrodes sufficient to bring about oxidation or reduction of the analyte or of a mediator in an analyte-detection redox system, thereby forming a chemical potential gradient of the analyte or mediator between the two electrodes;

(c) after the gradient is established, discontinuing the applied potential and obtaining an analyte-independent signal reflecting relaxation of the chemical potential gradient;

(d) obtaining an analyte-dependent signal during the application of the potential from measurement of a current transient before a steady state current is reached, and

(e) correcting the analyte-dependent signal obtained in step (d) using the analyte-independent signal obtained in step (c) to obtain a corrected analyte-dependent signal indicative of the presence of the selected analyte in the sample.

9. The method of claim 8, wherein the two electrodes of the conduction cells are less than 200 microns apart.

10. The method of claim 8, wherein the two electrodes of the conduction cell are in a coplanar arrangement.

11. The method of claim 8, wherein the two electrodes of the conduction cell have different areas.

12. The method of claim 8, wherein the potential applied in step (b) is time-invariant.

13. The method of claim 12, wherein the two electrodes of the conduction cells are less than 200 microns apart.

14. The method of claim 12, wherein the two electrodes of the conduction cell are in a coplanar arrangement.

15. The method of claim 12, wherein the two electrodes of the conduction cell have different areas.

16. The method of claim 8, wherein the analyte-independent measurement is the time from the removal of the applied potential for the measured potential to reach a predetermined value.

17. The method of claim 8, wherein the analyte-independent measurement is the potential at a predetermined time after the removal of the applied potential.

18. The method of claim 8, wherein the analyte-independent measurement is a measure of the rate of decay of the potential after the removal of the applied potential.

19. The method of claim 18, wherein the measure of the rate of decay is the slope of a plot of potential versus time during a pre-determined time interval after the removal of the applied potential.

20. The method of claim 18, wherein the measure of the rate of decay is the slope of a plot of log(potential) versus time during a pre-determined time interval after the removal of the applied potential.

21. The method of claim 18, wherein the measure of the rate of decay is the slope of a plot of 1/(potential)² versus time during a pre-determined time interval after the removal of the applied potential.

22. A method for determining an effective transport parameter (P_T) for a sample disposed in an electrochemical cell, wherein the electrochemical cell comprises at least a first and second electrodes in contact with the sample, said method comprising the step of:

(a) applying an external potential between the first and second electrodes to generate a current and a chemical potential gradient in the sample between the first and second electrodes;

(b) interrupting the external potential to establish a zero current state, and

(c) observing the potential difference between the first and second electrodes after the interruption of the external potential,

wherein the observed potential difference provides a measure of the effective transport parameter P_T.

23. The method of claim 22, wherein the first and second electrodes are coplanar.

24. The method of claim 23, wherein the potential difference is observed to determine the time interruption of the removal of the applied potential for the measured potential to reach a predetermined value as the measure of P_T.

25. The method of claim 23, wherein the potential difference is observed to determine the potential at a predetermined time after the removal of the applied potential as the measure of P_T.

26. The method of claim 23, wherein the potential difference is observed to determine the rate of decay of the potential after the removal of the applied potential as a measure of P_T.

27. The method of claim 26, wherein the rate of decay is the slope of a plot of potential versus time during a pre-determined time interval after the removal of the applied potential.

28. The method of claim 26 wherein the measure of the rate of decay is the slope of a plot of log(potential) versus time during a pre-determined time interval after the removal of the applied potential.

29. The method of claim 22, wherein the step of interrupting the potential is performed by creating an open circuit between the electrodes.

30. The method of claim 29, wherein the first and second electrodes are coplanar.

31. The method of claim 30, wherein the potential difference is observed to determine the time interruption of the removal of the applied potential for the measured potential to reach a predetermined value as the measure of P_T.

32. The method of claim 31, wherein the potential difference is observed to determine the potential at a predetennined time after the removal of the applied potential as the measure of P_T.

33. The method of claim 30, wherein the potential difference is observed to determine the rate of decay of the potential after the removal of the applied potential as a measure of P_T.

34. The method of claim 33, wherein the rate of decay is the slope of a plot of potential versus time during a pre-determined time interval after the removal of the applied potential.

35. The method of claim 33 wherein the measure of the rate of decay is the slope of a plot of log(potential) versus time during a pre-determined time interval after the removal of the applied potential.

36. The method of claim 22, wherein the step of interrupting the potential is performed by placing a high impedance component into the circuit between the electrodes.

37. The method of claim 36, wherein the first and second electrodes are coplanar.

38. The method of claim 37, wherein the potential difference is observed to determine the time interruption of the removal of the applied potential for the measured potential to reach a predetermined value as the measure of P_T.

39. The method of claim 37, wherein the potential difference is observed to determine the potential at a predetermined time after the removal of the applied potential as the measure of P_T.

40. The method of claim 37, wherein the potential difference is observed to determine the rate of decay of the potential after the removal of the applied potential as a measure of P_T.

41. The method of claim 40, wherein the rate of decay is the slope of a plot of potential versus time during a pre-determined time interval after the removal of the applied potential.

42. The method of claim 41 wherein the measure of the rate of decay is the slope of a plot of log(potential) versus time during a pre-determined time interval after the removal of the applied potential.