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 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.