Abnormal output detection system for a biosensor

• US 8,234,076 B2
• Filed: 10/17/2008
• Issued: 07/31/2012
• Est. Priority Date: 05/08/2006
• Status: Active Grant

• Current Assignee: Ascensia Diabetes Care Holdings AG (PHC Holdings Corporation)
• Original Assignee: Bayer Healthcare LLC (Bayer AG)
• Inventors: Carpenter, Scott, Nelson, Christine D., Wu, Huan-Ping
• Primary Examiner(s): Negin, Russell S
• Application Number:
  US12/253,440
• Publication Number:
  US 20090099787A1
• Time in Patent Office: 1,383 Days
• Field of Search: None
• US Class Current: 702/19
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/14546 for measuring analytes not otherwise provided for, e.g. ions, cytochromes
• CPC Class Codes: A61B 5/1486 using enzyme electrodes, e.g. with immobilised oxidase
• CPC Class Codes: C12Q 1/001 Enzyme electrodes
• 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: G16B 20/00 ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
• CPC Class Codes: G16B 5/00 ICT specially adapted for modelling or simulations in systems biology, e.g. gene-regulatory networks, protein interaction networks or metabolic networks
• CPC Class Codes: G16C 20/10 Analysis or design of chemical reactions, syntheses or processes

Abstract

A biosensor has an abnormal output detection system that determines whether an output signal from the redox reaction of an analyte has a normal or abnormal shape or configuration. The abnormal output detection system improves the accuracy and precision of the biosensor in determining whether an output signal has a shape or configuration that may not provide an accurate and/or precise analysis of a biological fluid. The biosensor generates an output signal in response to the redox reaction of the analyte. The biosensor normalizes the output signal and compares the normalized output signal with one or more control limits. The biosensor may generate an error signal when the normalized output signal is not within the control limits.

Claims

1. A method for increasing biosensor precision and/or accuracy, comprising:

applying a pulsed input signal to a sample of a biological fluid, the pulses of the input signal separated by relaxations where the electrical signal is off;

generating an output signal from a redox reaction of an analyte in the sample, where the output signal is responsive to the pulses of the input signal;

measuring the output signal from the redox reaction of the analyte in the sample;

normalizing the output signal from the redox reaction of the analyte in the sample, where the output signal is responsive to an analyte concentration in the sample;

comparing the normalized output signal from at least two of the pulses separated by relaxations to at least one control limit, where the at least one control limit represents an acceptable variation of the normalized output signal; and

generating an error signal when the normalized output signal is not within the at least one control limit.

2. The method of claim 1, where the normalizing includes determining a difference between at least one base output value and at least two measured output values of the output signal, where the at least one base output value is used in the normalizing of the at least two measured output values.

3. The method of claim 2, where the input signal includes a gated amperometric input signal including pulses and the output signal is responsive to the pulses of the gated amperometric input signal.

4. The method of claim 3, where the gated amperometric input signal comprises at least five pulses.

5. The method of claim 4, where the normalized current value of the fourth pulse, R₄, is represented by the following equation:

6. The method of claim 5, where R₄ is greater than or equal to 0.45, and where R₄ is less than or equal to 0.85.

7. The method of claim 4, where the normalized current value of the fifth pulse, R₅, is represented by the following equation:

8. The method of claim 7, where R₅ is greater than or equal to 0.45, and where R₅ is less than or equal to 0.85.

9. The method of claim 4, where the ratio of the normalized current value of the fourth pulse to the normalized current value of the fifth pulse is represented by the following equation:

10. The method of claim 9, where Ratio is greater than or equal to 0.75, and where Ratio is less than or equal to 1.25.

11. The method of claim 2, where the at least one base output value is a different measured output value of the output signal than at least one of the at least two measured output values.

12. The method of claim 1, where the normalizing includes dividing at least one output value of the output signal by a first output value from a pulse of the output signal.

13. The method of claim 1, where the sample of the biological fluid is whole blood, further comprising:

separating normalized current values of the output signal in response to underlying current profiles; and

selecting the at least one control limit to include an acceptable variation of the normalized current values about a mean using statistical techniques.

14. The method of claim 1, where a normalized output signal within the at least one control limit provides an accurate and/or precise analysis of the biological fluid and where a normalized output signal not within the at least one control limit does not provide an accurate and/or precise analysis of the sample of the biological fluid.

15. The method of claim 1, further comprising determining the at least one control limit from a statistical analysis of laboratory results.

16. The method of claim 1, further comprising detecting when the sample connects at least two electrodes with a polling input signal, where the input signal comprises the polling input signal and an assay input signal.

17. The method of claim 16, where the polling input signal has a polling pulse width of less than about 300 ms, and where the polling input signal has a polling pulse interval of less than about 1 sec.

18. The method of claim 17, where the polling input signal has a polling pulse width in the range of about 0.5 ms through about 75 ms, and where the polling input signal has a polling pulse interval in the range of about 5 ms through about 300 ms.

19. The method of claim 16, where the assay input signal has an assay pulse width of less than about 5 sec, and where the assay input signal has an assay pulse interval of less than about 15 sec.

20. The method of claim 19, where the assay input signal has an assay pulse width in the range of about 0.1 sec through about 3 sec, and where the assay input signal has an assay pulse interval in the range of about 0.2 sec through about 6 sec.

21. The method of claim 16, further comprising:

applying the polling input signal during a polling period, where the polling period is less than about 180 sec; and

applying the assay input signal during an assay period, where the assay period is less than about 180 sec.

22. The method of claim 16, further comprising:

applying the polling input signal during a polling period, where the polling period is in the range of about 0.1 sec through about 10 sec; and

applying the assay input signal during an assay period, where the assay period is in the range of about 1 sec through about 100 sec.

23. The method of claim 16, further comprising:

applying a polling input signal to the sample for about 1.25 sec where the polling input signal has a polling pulse width of about 5-10 ms and a polling pulse interval of about 125 ms; and

applying an assay input signal to the sample for about 7 sec, where the assay input signal has an assay pulse width of about 1 sec and an assay pulse interval of about 1.5 sec.

24. The method of claim 23, where the polling input signal has a potential of about 400 mV, where the assay input signal has a first pulse with a potential of about 400 mV, where the assay input signal has at least one other pulse with a potential of about 200 mV.

25. The method of claim 16, further comprising applying the assay input signal when a polling output signal is greater than or equal to a polling threshold.

26. The method of claim 25, where the polling threshold is about 250 nA.

27. The method of claim 1, where the measuring the output signal comprises measuring the output signal intermittently.

28. The method of claim 27, where the measuring the output signal intermittently comprises measuring at least eight current values in at least one pulse of the output signal.