Voltammetric systems for assaying biological analytes

• US 8,871,079 B2
• Filed: 09/12/2012
• Issued: 10/28/2014
• 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): DIETERLE, JENNIFER M
• Application Number:
  US13/611,557
• Publication Number:
  US 20130240377A1
• Time in Patent Office: 776 Days
• Field of Search: 20440301-40315, 205/777.5, 205/778, 205/792, 422/82.01, 422/68.1, 435/287.1, 435/14
• 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 the concentration of an analyte in a sample, comprising:

oxidizing or reducing the analyte,

applying a voltammetric forward linear scan to the sample,

where the forward linear scan applies a changing voltage, and

the sample comprises at least one species of a redox pair;

measuring current as a function of the changing voltage;

applying a data treatment to the measured current; and

determining a concentration of an analyte in the sample in response to the data treatment.

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 2, where the sample comprises blood.

4. The method of claim 1, further comprising applying a voltammetric reverse linear scan to the sample at a reversing point of the forward linear scan.

5. The method of claim 4, where the voltammetric forward and reverse linear scans comprise an acyclic scan.

6. The method of claim 4, where the voltammetric forward and reverse linear scans comprise a cyclic scan.

7. The method of claim 4, where the reverse scan comprises at least 25 mV of steady-state region.

8. The method of claim 7, where the steady-state region of the scan comprises a change in electrochemical current with respect to voltage of at most ±

10%.

9. The method of claim 4, where the reversing point is selected to provide from 25 to 400 mV of steady-state region.

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

11. The method of claim 10, further comprising changing the voltage of the forward scan at a rate of at least 500 mV/second.

12. The method of claim 1, where the forward scan comprises a scan range from 400 to 1000 mV.

13. The method of claim 1, where the forward scan comprises at least one voltage providing at least a 100:

1 concentration ratio between two species of a redox pair.

14. The method of claim 1, where the forward scan comprises at least one potential at a working electrode of at least 180 mV.

15. The method of claim 1, where the data treatment is selected from the group consisting of a semi-integral data treatment, a derivative data treatment, a semi-derivative data treatment, and combinations thereof.

16. The method of claim 1, where the data treatment comprises a semi-integral data treatment.

17. The method of claim 16, where the applying the data treatment comprises semi-integrating the currents from the forward linear scan and determining a steady-state semi-integral current.

18. The method of claim 16, where the semi-integral data treatment separates at least one steady-state current from at least one hematocrit-affected equilibrium current.

19. The method of claim 16, where the semi-integral data treatment comprises at least one half-step integration.

20. The method of claim 16, where the semi-integral data treatment lacks a time-dependence factor.

21. The method of claim 16, further comprising determining a ratio of a peak current value to a steady-state current value in response to a hematocrit compensation.

22. The method of claim 1, where the data treatment comprises a semi-derivative data treatment.

23. The method of claim 22, where the semi-derivative data treatment transforms at least a portion of a voltammetric current region into a peak.

24. The method of claim 1, where the data treatment comprises a derivative data treatment.

25. The method of claim 24, where the derivative data treatment comprises hematocrit compensation comprising dividing a negative peak by a positive peak.

26. The method of claim 1, where the determining comprises hematocrit compensation.

27. The method of claim 26, where the hematocrit compensation comprises determining a ratio of a peak current value to a steady-state current value.

28. The method of claim 1, where the determining comprises inputting at least one steady-state current value into a compensation equation.

29. The method of claim 1, where the determined concentration of the analyte in the sample provides a concentration value closer to that obtained from a reference instrument than if coulometry were substituted for the voltammetric forward linear scan.