Methods of detecting high antioxidant levels during electrochemical measurements and failsafing an analyte concentration therefrom

• US 9,594,045 B2
• Filed: 09/11/2015
• Issued: 03/14/2017
• Est. Priority Date: 03/15/2013
• Status: Active Grant

• Current Assignee: Roche Diabetes Care Inc. (Roche Holding AG)
• Original Assignee: Roche Diabetes Care Inc. (Roche Holding AG)
• Inventors: Buck, Harvey B. Jr., Carpenter, Scott E., Pan, Zheng Zheng
• Primary Examiner(s): Noguerola, Alexander
• Application Number:
  US14/852,114
• Publication Number:
  US 20160011140A1
• Time in Patent Office: 550 Days
• US Class Current: 1/1
• 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

Methods are disclosed for measuring an analyte concentration in a fluidic sample. Such methods further allow one to provide an error code or correct and/or compensate for interferents such as an antioxidant before providing an analyte concentration. The measurement methods utilize information obtained from test sequences having at least one DC block, such as a slow-ramped bi-polar waveform, where a closed circuit condition is maintained during the DC block. The methods use information relating to status of a redox mediator feature during the electrochemical analysis to provide an antioxidant failsafe if the antioxidant is interfering with the analyte concentration. Also disclosed are devices, apparatuses and systems incorporating the various measurement methods.

Claims

1. A method of electrochemically measuring an analyte in a fluid sample in the presence of an antioxidant, the method comprising the steps of:

applying an electrical test sequence to an electrochemical biosensor, the biosensor comprising;

an electrode system,

a reagent including a redox mediator in electrical communication with the electrode system, and

a receptacle configured to contact the fluid sample provided to the biosensor,

with the fluid sample in fluidic contact with the reagent, wherein the test sequence comprises at least two direct current (DC) blocks, wherein a first DC block includes a slow-ramp bi-polar (SRBP) waveform having at least one SRBP recovery potential, wherein a second DC block includes a sequence alternating between at least one excitation potential and at least one recovery potential, and wherein a closed circuit condition of the electrode system is maintained during the at least two DC blocks;

measuring current response information to the first DC block, including information from the at least one SRBP recovery potential;

measuring current response information to the second DC block, including the at least one excitation potential and the at least one recovery potential;

evaluating quantitatively a level of the antioxidant present in the fluid sample based at least in part upon current response information to the SRBP waveform; and

determining an analyte concentration of the fluid sample based at least in part upon current response information from the excitation current response and the recovery current response, the determining compensating for the antioxidant.

2. The method of claim 1 further comprising the step of displaying a failsafe if the level of the antioxidant is above a predetermined threshold.

3. The method of claim 2, wherein the failsafe is an error code or a specific failsafe message.

4. The method of claim 1, wherein the redox mediator is a nitrosoanaline (NA)-derived redox mediator.

5. The method of claim 4, wherein the NA-derived redox mediator is N,N-bis(hydroxyethyl)-3-methoxy-4-nitrosoanaline hydrochloride.

6. The method of claim 1, wherein the SRBP waveform is at least one of a triangular potential waveform, a trapezoidal potential waveform or a sinusoidal potential waveform.

7. The method of claim 1, wherein the SRBP waveform alternates between about −

450 mV to about +450 mV at equal ramp rates, or wherein the SRBP waveform alternates between about −

450 mV to about +450 mV at two different ramp rates.

8. The method of claim 7, where the ramp rates are between about 3 mV/msec and about 9 mV/msec.

9. The method of claim 1, wherein the second DC block alternates between about +450 mV to about 0 mV for the at least one excitation potential to the at least one recovery potential.

10. The method of claim 1, wherein the second DC block is applied prior to the at least one DC block.

11. The method of claim 1, wherein the test sequence further comprises an alternating current (AC) block.

12. The method of claim 11, wherein the test sequence includes in ordered sequence the AC block, the second DC block, and the first DC block.

13. The method of claim 1, wherein the antioxidant is ascorbate.

14. The method of claim 1, wherein the biosensor is configured for operation in connection with a self-monitoring blood glucose (SMBG) system.

15. The method of claim 1, wherein the biosensor is configured for operation in connection with a self-monitoring blood ketone (SMBK) system.

16. A method of electrochemically measuring an analyte in a fluid sample that may have one or more interferents, the method comprising the steps of:

applying an electrical test sequence to an electrochemical biosensor, the biosensor comprising;

an electrode system,

a reagent including a redox mediator in electrical communication with the electrode system, and

a receptacle configured to contact the fluid sample provided to the biosensor,

with the fluid sample in fluidic contact with the reagent, wherein the test sequence includes a first signal component configured to provide a current response varying as a function of concentration of one or more interferents in the fluid sample, and wherein the test sequence further a second signal component comprising a sequence of potential pulses alternating between an excitation potential configured to produce an excitation current response associated with an electrochemical reaction of an analyte and the reagent and a recovery potential configured to produce a recovery current response associated with a closed circuit recovery of the biosensor;

performing a reagent chemistry health failsafe check based upon an evaluation of the current response to the first signal component indicating the concentration of the one or more interferents; and

determining concentration of the analyte based upon the excitation current response information and the recovery current response information to the second signal component.

17. The method of claim 16, wherein the first signal component is configured to provide a current response varying as a function of concentration of one or more interferents in the fluid sample comprises a slow-ramp bi-polar (SRBP) waveform.

18. The method of claim 17, wherein the SRBP waveform is at least one of a triangular potential waveform, a trapezoidal potential waveform or a sinusoidal potential waveform.

19. The method of claim 16, wherein the redox mediator is a nitrosoanaline (NA)-derived redox mediator.

20. The method of claim 19, wherein the NA-derived redox mediator is N,N-bis(hydroxyethyl)-3-methoxy-4-nitrosoanaline hydrochloride.

21. The method of claim 16 further comprising the step of:

evaluating quantitatively a level of the one or more interferents present in the fluid sample based at least in part upon current response information of the current response, wherein at least one of the one or more interferents is an antioxidant.

22. The method of claim 21, wherein the antioxidant is ascorbate.

23. The method of claim 16, wherein the determining concentration of the analyte step compensates for the at least one interferent.

24. The method of claim 16, wherein if the performing the reagent chemistry health failsafe check step indicates a potential for a clinically significant bias, the analyte concentration is not displayed but instead is failsafed with an appropriate message of suspected interference, reagent layer failure, or even a general biosensor failure.

25. A method of electrochemically measuring an analyte in a fluid sample and providing an antioxidant failsafe, the method comprising the steps of:

evaluating a level of the antioxidant present in the fluid sample based at least in part upon current response information to a slow-ramp bi-polar (SRBP) waveform applied under a closed circuit condition, wherein the SRBP waveform alternates between about −

450 mV to about +450 mV at equal ramp rates, or wherein the SRBP waveform alternates between about −

450 mV to about +450 mV at different ramp rates, wherein the ramp rates are between about 3 mV/msec and about 9 mV/msec, and wherein a failsafe is displayed if the level of the antioxidant is above a predetermined threshold.

26. The method of claim 25, wherein the failsafe is an error code or a specific failsafe message.

27. The method of claim 25, wherein the failsafe is based upon a presence or absence of an expected redox mediator status.

28. The method of claim 27, wherein the redox mediator is a nitrosoanaline (NA)-derived redox mediator.

29. The method of claim 28, wherein the NA-derived redox mediator is N,N-bis(hydroxyethyl)-3-methoxy-4-nitrosoanaline hydrochloride.

30. The method of claim 29, wherein the expected redox mediator status is a quinonediimine (QDI) feature, and wherein the QDI feature is absent.

31. The method of any claim 25, wherein the SRBP waveform is at least one of a triangular potential waveform, a trapezoidal potential waveform or a sinusoidal potential waveform.

32. The method of claim 25, wherein the antioxidant is ascorbate.

33. The method of claim 32, wherein the predetermined threshold is about 3 mg/dL of ascorbate in the fluid sample.