Voltammetric systems for assaying biological analytes
View Patent ↗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.
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.