Method and apparatus for assay of electrochemical properties

• US 7,501,052 B2
• Filed: 08/23/2004
• Issued: 03/10/2009
• 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: Harding, Ian, Iyengar, Sridhar G.
• Primary Examiner(s): NOGUEROLA, ALEXANDER STEPHAN
• Application Number:
  US10/924,510
• Publication Number:
  US 20050109637A1
• Time in Patent Office: 1,660 Days
• Field of Search: 20440301-40315, 205/777.5, 205/778, 205/792, 205/775
• 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 in the sample is evaluated in an 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. This correction allows an improved measurement of analyte concentration because it corrects for device-specific and test specific factors such as transport (mobility) of analyte and/or mediator, effective electrode area, and electrode spacing (and as a result, sample volume), without need for separate calibration values. The analysis can be performed using disposable test strips in a hand held meter, for example for glucose testing.

Claims

1. 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 or current 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 or current and obtaining an analyte-independent signal reflecting relaxation of the chemical potential gradient;

(d) optionally applying a potential or current between the electrodes after the analyte-independent signal is obtained;

(e) obtaining an analyte-dependent signal during the application of the potential or current in step (b) or step (d) or both, and

(f) correcting the analyte-dependent signal obtained in step (e) 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.

2. The method of claim 1, wherein a potential is applied between the electrodes in step (b), and current generated as a result of this applied potential is measured as the analyte-dependent signal.

3. The method of claim 2, wherein the potential is applied until a steady state condition is achieved, and the current is then measured.

4. The method of claim 2, wherein the current is measured before a steady state condition is achieved.

5. The method of claim 1, wherein a current is maintained between the electrodes in step (b), and potential generated as a result of this current is measured as the analyte-dependent signal.

6. The method of claim 5, wherein the current is maintained until a steady state condition is achieved, and the potential is then measured.

7. The method of claim 5, wherein the potential is measured before a steady state condition is achieved.

8. The method of claim 1, wherein the chemical potential gradient prior to relaxation extends across at least 10% of the distance between the electrodes.

9. The method of claim 8, wherein the chemical potential gradient prior to relaxation extends across at least 80% of the distance between the electrodes.

10. The method of claim 9, wherein a potential is applied between the electrodes in step (b), and current generated as a result of this applied potential is measured as the analyte-dependent signal.

11. The method of claim 10, wherein the potential is applied until a steady state condition is achieved, and the current is then measured.

12. The method of claim 10, wherein the current is measured before a steady state condition is achieved.

13. The method of claim 9, wherein a current is maintained between the electrodes in step (b), and potential generated as a result of this current is measured as the analyte-dependent signal.

14. The method of claim 13, wherein the current is maintained until a steady state condition is achieved, and the potential is then measured.

15. The method of claim 13, wherein the potential is measured before a steady state condition is achieved.

16. A method for determining the effective separation distance between a first electrode and a second electrode in an electrochemical cell, the method comprising the steps of:

applying an external force in the form of an applied potential or an applied current to generate a chemical potential gradient between the first electrode and the second electrode;

stopping the application of the external force;

observing the decay of the chemical potential gradient as a function of time; and

computing the effective electrode separation distance from the observed decay of the chemical potential gradient.

17. A method for determining an effective transport property between a first electrode and a second electrode in an electrochemical cell, the method comprising the steps of:

applying an external force in the form of an applied potential or a current to generate a chemical potential gradient between the first electrode and the second electrode;

stopping the application of the external force;

observing the decay of the chemical potential gradient as a function of time; and

computing an effective transport property of the electrochemical system from the observed decay of the chemical potential gradient.

18. An apparatus for determining the presence of an analyte in a sample disposed in an electrochemical cell said electrochemical cell comprising two electrodes between which the sample is placed for analysis, said apparatus comprising:

(a) a housing having a space for receiving the electrochemical cell;

(b) means for applying a potential or a current between the two electrodes of the electrochemical cell when it is received within the housing;

(c) means for measuring oxidation or reduction of an analyte or a mediator in an analyte-detection system occurring within the electrochemical cell when the potential or current is being applied;

(d) means for switching the potential or current off after a period of time during which a chemical potential gradient is established between the two electrodes;

(e) means for monitoring the decay of the chemical potential gradient after the potential or current is switched off;

(f) programmed data processing means for combining the measured oxidation or reduction with the monitored decay to produce an indication of the presence of the analyte in the sample; and

(g) output means for conveying the indication of the presence of the analyte in the sample to a user.

19. The apparatus of claim 18, further comprising an electrochemical cell disposed within the housing.

20. The apparatus of claim 18, wherein the housing is of a size that can be held in a human hand.

21. The apparatus of claim 20, further comprising an electrochemical cell disposed within the housing.

22. The apparatus of claim 21, wherein the electrochemical cell is a single use disposable test strip.