Method and apparatus for assay of electrochemical properties

• US 20050069892A1
• Filed: 02/10/2003
• Published: 03/31/2005
• Est. Priority Date: 02/10/2002
• 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 S.
• Granted Patent: US 7,601,249 B2
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: A61B 2562/04 Arrangements of multiple sensors of the same type
• CPC Class Codes: A61B 5/1468 using chemical or electrochemical methods, e.g. by polarographic means A61B5/1486 takes precedence
• CPC Class Codes: A61B 5/1473 invasive, e.g. introduced into the body by a catheter A61B5/1482 takes precedence
• CPC Class Codes: A61B 5/1495 Calibrating or testing of in-vivo probes
• CPC Class Codes: A61B 5/7203 for noise prevention, reduction or removal
• CPC Class Codes: G01N 17/02 Electrochemical measuring systems for weathering, corrosion or corrosion-protection measurement
• CPC Class Codes: G01N 27/26 by investigating electrochemical variables; by using electrolysis or electrophoresis
• CPC Class Codes: G01N 27/3273 Devices therefor, e.g. test element readers, circuitry details not specific to biochemical electrodes G01N33/4875
• CPC Class Codes: G01N 27/3274 Corrective measures, e.g. error detection, compensation for temperature or hematocrit, calibration coding of calibration information G01N33/48771

Abstract

A method for monitoring a select analyte in a sample in an electrochemical system. The method includes applying to the electrochemical system a time-varying potential superimposed on a DC potential to generate a signal; and discerning from the signal a contribution from the select analyte by resolving an estimation equation based on a Faradaic signal component and a nonfaradaic signal component.

Claims

1. A method for monitoring a select analyte in a sample in an electrochemical system, comprising:

applying to the electrochemical system a time-varying potential superimposed on a DC potential to generate a signal; and

discerning from the signal a contribution from the select analyte by resolving an estimation equation based on a Faradaic signal component and a nonfaradaic signal component.

2. The method of claim 1, wherein the nonfaradaic signal component is indicative of an environmental factor of the electrochemical system.

3. The method of claim 1, wherein the Faradaic signal component is indicative of a concentration of the select analyte.

4. The method of claim 1, wherein the DC potential is approximately 0 volts.

5. The method of claim 1, wherein the time-varying potential comprises a substantially sinusoid potential waveform of approximately less than 50 mV peak-to-peak amplitude.

6. The method of claim 1, wherein the time-varying potential is a waveform used in cyclic voltammetry.

7. The method of claim 1, wherein the time-varying potential is a step function.

8. The method of claim 1, wherein the time-varying potential has a variation greater than 50 mV and capacitive information is extracted by an estimation equation.

9. The method of claim 1, wherein capacitive information is extracted from the nonfaradaic signal component by spectral analysis.

10. The method of claim 1, wherein the time-varying potential is a sinusoid potential and the estimation equation uses information from a fundamental frequency of the signal.

11. A method of determining a volume of a sample present in an electrochemical system, wherein the electrochemical system includes an electrode having a surface, wherein the surface includes a contact portion and a non-contact portion, wherein the contact portion of the electrode is in electrolytic contact with the sample and the non-contact portion of the electrode is not in contact with the sample, comprising:

applying a potential stimulus to the system to generate a signal;

measuring the signal;

computing at least one parameter of all or some portion of the generated signal; and

determining a surface area of the contact portion by resolving an estimation equation based on the at least one parameter, wherein the surface area corresponds to a portion in electrolytic contact with the sample.

12. The method of claim 11, wherein the at least one parameter contains capacitive information about the electrochemical system.

13. The method of claim 11, wherein the volume of the sample present in an electrochemical cell is resolved by an estimation equation based on the surface area and dimensions of the electrochemical cell.

14. The method of claim 11, wherein the electrochemical system is comprised of at least two planar electrodes in a parallel plate geometry.

15. The method of claim 11, wherein the electrochemical system is comprised of at least two electrodes on a support substrate lying on the same geometric plane.

16. A method of determining a plurality of environmental factors in an electrochemical system, wherein the electrochemical system includes an electrode having a surface, wherein the surface includes a contact portion and a non-contact portion, wherein the contact portion of the electrode is in electrolytic contact with the sample and the non-contact portion of the electrode is not in contact with the sample, comprising:

applying a time-varying potential stimulus to the system to generate a signal;

measuring the signal;

computing at least one parameter of all or some portion of the signal;

and determining values of the plurality of environmental factors by resolving an estimation equation based on the at least one parameter.

17. The method of claim 16, wherein the at least one parameter contains capacitive information about the electrochemical system.

18. The method of claim 16, wherein the electrochemical system includes an electrode having a surface area, wherein the surface area in electrolytic contact with the sample is determined by resolving the estimation equation based on the at least one parameter.

19. The method of claim 16, wherein the electrochemical system includes an electrode having an area, wherein the area is determined by resolving the estimation equation based on the at least one parameter.

20. The method of claim 16, wherein the electrochemical system includes an electrode having a quantity of fouling, wherein the fouling is determined by resolving the estimation equation based on the at least one parameter

21. The method of claim 16, wherein the time-varying potential is a DC bias potential with a sinusoidal potential superimposed.

22. The method of claim 21, wherein the DC bias is approximately 0 volts.

23. The method of claim 21, wherein the estimation equation extracts capacitive information from the signal.

24. The method of claim 21, wherein the sinusoidal potential has less than approximately 50 mV peak-to-peak amplitude.

25. The method of claim 17, wherein the capacitive information is based on an imaginary component of a complex immittance of the electrochemical system

26. The method of claim 17, wherein the time-varying current has an amplitude, wherein the capacitive information is based on the amplitude.

27. The method of claim 17, wherein the capacitive information is based on a rate of decay of the signal.

28. The method of claim 17, wherein the capacitive information is based on a rate of rise of the signal.

29. The method of claim 16, wherein the electrochemical system includes a select analyte in a sample, wherein a volume of the sample is determined.

30. The method of claim 16, wherein the electrochemical system includes a select analyte in a sample, wherein the select analyte is glucose.

31. The method of claim 16, wherein the electrochemical system includes a select analyte in a sample, wherein the select analyte is a carbohydrate.

32. The method of claim 16, wherein the electrochemical system includes a select analyte in a sample, wherein the select analyte is a mediator species.

33. The method of claim 32, wherein the mediator species is a ferrocene/ferrocenium couple.

34. The method of claim 32, wherein the mediator species is a ferrocyanide/ferricyanide couple.

35. A method of estimating an analyte concentration in a sample in an electrochemical system, comprising:

applying a time-varying potential to the system to generate a signal;

measuring the signal;

computing at least one parameter of all or some portion of the signal; and

determining the analyte concentration by resolving an estimation equation based on Faradaic and nonfaradaic signal information.

36. The method of claim 35, wherein the electrochemical system includes an electrode, wherein an area of the electrode is determined by resolving the estimation equation based on the at least one parameter.

37. The method of claim 35, wherein the electrochemical system includes an electrode having a quantity of fouling, wherein the fouling is determined by resolving the estimation equation based on the at least one parameter.

38. The method of claim 35, wherein the extent of electrolytic contact with the sample is determined by resolving an estimation equation based on the at least one parameter.

39. The method of claim 35, wherein the at least one parameter contains capacitive information about the electrochemical system.

40. An apparatus comprising:

a potentiostat circuit for applying a potential waveform to and detecting a resulting current from an electrochemical system; and

at least one memory having program instructions and a processor configured to execute the program instructions to perform the operations of applying a time-varying potential stimulus waveform to the electrode system to generate a current signal;

measuring the generated signal;

computing at least one parameter of a Faradaic component of the measured signal;

computing at least one parameter of a nonfaradaic component of the measured signal;

determining a concentration of a select analyte by use of the at least one Faradaic parameter and the at least one nonfaradaic parameter to resolve an estimation equation for the select analyte; and

determining a value of an environmental factor in the electrochemical system by use of the at least one Faradaic parameter and the at least one nonfaradaic parameter to resolve the estimation equation for the value of the environmental factor.

41. A method of constructing estimation equations for monitoring a select analyte in a sample, comprising:

selecting a time-varying potential waveform to generate a signal when applied to an electrochemical system;

applying the waveform to samples containing multiple different concentrations of the analyte and measuring the resulting signal;

applying the waveform to systems with multiple different environmental factors;

selecting features of the signal to use as parameters;

computing at least one parameter of the signal based on a Faradaic signal component;

computing at least one parameter of the signal based on a nonfaradaic signal component; and

constructing a set of equations that relates analyte concentration and values of environmental factors to the at least one Faradaic parameter and to the at least one nonfaradaic parameter.

42. A method of determining the identity of a sample in electrolytic contact with an electrochemical system, comprising:

applying a time-varying potential to the system to generate a signal;

measuring the generated signal;

computing at least one parameter of all or some portion of the generated signal; and

determining the identity of the sample by comparing the at least one parameter to known parameter values of known samples.

43. The method of claim 42, wherein the electrochemical system is comprised of multiple electrodes in a geometric arrangement.

44. The method of claim 42, wherein the amounts of different samples present in an electrochemical system are estimated.

45. The method of claim 42, wherein the number of electrodes in electrolytic contact with a particular sample is used to estimate the volume of that particular sample.