Voltammetric systems for assaying biological analytes

• US 8,287,717 B2
• Filed: 05/16/2005
• Issued: 10/16/2012
• Est. Priority Date: 05/14/2004
• Status: Active Grant

• Current Assignee: Ascensia Diabetes Care Holdings AG (PHC Holdings Corporation)
• Original Assignee: Bayer Healthcare LLC (Bayer AG)
• Inventors: Wu, Huan-Ping
• Primary Examiner(s): Barton, Jeffrey T
• Assistant Examiner(s): DIETERLE, JENNIFER M
• Application Number:
  US11/596,309
• Publication Number:
  US 20080105568A1
• Time in Patent Office: 2,710 Days
• Field of Search: 20440301-40315, 205/777.5, 205/778, 205/792, 205/775, 205/779, 205/787, 600309-367, 436 62- 71, 436500-548, 422400-430, 422500-570, 422/82.01, 435 4- 4052, 435/39, 435/14, 324/76.11, 702/19
• US Class Current: 205/777.5
• CPC Class Codes: C12Q 1/005 involving specific analytes or enzymes including groups of enzymes, e.g. oxydases; C12Q1/004 takes precedence
• CPC Class Codes: G01N 27/327 Biochemical electrodes , e.g. electrical or mechanical details for in vitro measurements
• CPC Class Codes: G01N 27/3272 Test elements therefor, i.e. disposable laminated substrates with electrodes, reagent and channels optical biosensors G01N33/52
• 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 27/48 using polarography, i.e. measuring changes in current under a slowly-varying voltage
• CPC Class Codes: G01N 27/49 Systems involving the determination of the current at a single specific value, or small range of values, of applied voltage for producing selective measurement of one or more particular ionic species

Abstract

The present invention relates to systems, methods, and devices for determining the concentration of an analyte in a sample. The use of linear, cyclic, or acyclic voltammetric scans and/or semi-integral, derivative, or semi-derivative data treatment may provide for increased accuracy when determining the concentration of an analyte in a sample. Hematocrit compensation in combination with the data treatments may reduce the hematocrit effect with regard to a glucose analysis in whole blood. In another aspect, fast scan rates may reduce the hematocrit effect.

Claims

1. A method of determining a concentration of an analyte in a sample, comprising:

contacting the sample and at least one species of a redox pair;

applying an acyclic scan to the sample,

where the acyclic scan has forward and reverse scans that apply a changing voltage, and

the at least one species of the redox pair undergoes oxidation and/or reduction during the acyclic scan;

measuring current as a function of the changing voltage; and

determining a concentration of an analyte in the sample from the current.

2. The method of claim 1, where the analyte is selected from the group consisting of glucose, cholesterol, triglycerides, lactate, pyruvate, alcohol, bilirubin, uric acid, NAD(P)H, and carbon monoxide.

3. The method of claim 1, wherein the analyte is glucose.

4. The method of claim 1, wherein the forward scan starts at a different voltage than where the reverse scan ends.

5. The method of claim 1, wherein the acyclic scan comprises at least one of a forward scan with more of a current peak than the reverse scan, a reverse scan with more of a current peak than the forward scan, a forward scan starting at most ±

20 mV away from the formal potential E°

′

of the redox pair, and forward and reverse scans substantially excluding the oxidation and reduction peaks of the redox pair.

6. The method of claim 1, wherein the acyclic scan further comprises forward and reverse linear scans within the steady-state region of the redox pair, the scans having a scan range from 10 to 200 mV.

7. The method of claim 1, wherein the acyclic scan further comprises a scan range from 400 to 600 mV.

8. The method of claim 1, wherein the acyclic scan further comprises a scan range from 600 to 1000 mV.

9. The method of claim 1, wherein the acyclic scan further comprises a reversing point selected to provide from 25 to 400 mV of steady-state region.

10. The method of claim 1, further comprising terminating a reverse scan at a potential from 50 to 500 mV negative from a reversing point.

11. The method of claim 1, further comprising terminating a reverse scan when the current of the reverse scan deviates by at least 25% from a steady-state current.

12. The method of claim 1, wherein the acyclic scan comprises at least one voltage generating at least a 100:

1 concentration ratio between two species of the redox pair.

13. The method of claim 1, wherein the acyclic scan further comprises at least one potential at a working electrode of at least 180 mV.

14. The method of claim 1, further comprising inputting at least one steady-state current value into a compensation equation.

15. The method of claim 1, further comprising determining an analyte concentration with a concentration value closer to a reference analyte concentration obtained from a reference instrument than if coulometry were substituted for the acyclic scan.

16. The method of claim 1, where the acyclic scan substantially excludes oxidation and reduction peaks of the redox pair.

17. The method of claim 1, where the forward scan comprises more of a current peak than the reverse scan.

18. The method of claim 1, where the reverse scan comprises more of a current peak than the forward scan.

19. The method of claim 1, where the forward scan starts at most ±

20 mV away from the formal potential E°

′

of the redox pair.

20. The method of claim 1, where the changing voltage is applied continuously.

21. The method of claim 1, wherein the sample comprises a biological sample.

22. The method of claim 21, wherein the sample comprises whole blood.

23. The method of claim 1, further comprising changing the voltage of the acyclic scan at a rate of at least 176 mV/second.

24. The method of claim 23, further comprising changing the voltage of the acyclic scan at a rate of at least 500 mV/second.

25. The method of claim 1, further comprising changing the voltage of the acyclic scan at a rate of at most 175 mV/second.

26. The method of claim 25, further comprising changing the voltage of the acyclic scan at a rate of at most 50 mV/second.

27. The method of claim 1, wherein the acyclic scan further comprises at least 25 mV of steady-state region.

28. The method of claim 27, wherein the steady-state region of the scan comprises a change in electrochemical current with respect to voltage of at most ±

10%.

29. The method of claim 1, further comprising determining the analyte concentration in response to a semi-integral data treatment.

30. The method of claim 29, further comprising semi-integrating current values from the acyclic scan;

and determining a steady-state semi-integral current.

31. The method of claim 29, further comprising separating at least one steady-state current from at least one hematocrit-affected equilibrium current.

32. The method of claim 29, wherein the semi-integral data treatment comprises at least one half-step integration.

33. The method of claim 29, wherein the semi-integral data treatment lacks a time-dependence factor.

34. The method of claim 29, further comprising determining a ratio of a peak current value to a steady-state current value in response to a hematocrit compensation.

35. The method of claim 1, further comprising determining the analyte concentration in response to a derivative data treatment.

36. The method of claim 35, further comprising dividing a negative peak by a positive peak in response to a hematocrit compensation.

37. The method of claim 1, further comprising determining the analyte concentration in response to a semi-derivative data treatment.

38. The method of claim 37, further comprising transforming at least a portion of a voltammetric current region to a peak in response to the semi-derivative data treatment.