Determining analyte concentrations in biological fluids with abnormal output detection

• US 9,301,717 B2
• Filed: 06/28/2012
• Issued: 04/05/2016
• Est. Priority Date: 05/08/2006
• Status: Active Grant

• Current Assignee: Ascensia Diabetes Care Holdings AG (PHC Holdings Corporation)
• Original Assignee: Ascensia Diabetes Care Holdings AG (PHC Holdings Corporation)
• Inventors: Carpenter, Scott, Nelson, Christine D., Wu, Huan-Ping
• Primary Examiner(s): NEGIN, RUSSELL SCOTT
• Application Number:
  US13/536,310
• Publication Number:
  US 20120271559A1
• Time in Patent Office: 1,377 Days
• Field of Search: None
• US Class Current: 1/1
• 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 biosensor for determining an analyte concentration in a biological fluid, comprising:

a sensor strip having a sample interface on a base, where the sample interface is adjacent to a reservoir formed by the base; and

a measuring device having a processor connected to a sensor interface, where the sensor interface has electrical communication with the sample interface;

where the processor directs a signal generator to provide 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;

where the processor receives 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;

where the processor measures the output signal from the redox reaction of the analyte in the sample;

where the processor normalizes 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, the normalized output signal being indicative of the analyte concentration in the sample;

where the processor compares 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 at least one transition of the output signal from normal to abnormal;

where the processor generates an error signal when the normalized output signal is not within the at least one control limit, the error signal being indicative of an error in analysis of the analyte concentration in the sample; and

where the processor calculates a ratio of a first normalized current value from one of the pulses to a second normalized current value from another pulse.

2. The biosensor of claim 1, where the processor determines a difference between at least one base output value and at least two measured output values of the output signal, where the processor uses at least one base output value in the normalizing of the at least two measured output values.

3. The biosensor 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 biosensor of claim 3, where the output signal comprises at least five pulses.

5. The biosensor 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.

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

7. The biosensor of claim 5, where the normalized current value of the fifth pulse, R₅, is represented by the following equation:

8. The biosensor of claim 5, 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:

9. The biosensor of claim 1, where the processor divides at least one output value of the output signal by a first output value from a pulse of the output signal.

10. The biosensor of claim 1, where the at least one control limit is predetermined from a statistical analysis of laboratory results.

11. The biosensor of claim 1, where the input signal comprises a polling input signal and an assay input signal.

12. The biosensor of claim 11, where the polling input signal has a polling pulse width of less than about 300 ms and a polling pulse interval of less than about 1 sec.

13. The biosensor of claim 11, 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.

14. The biosensor of claim 11, where the processor applies the polling input signal during a polling period of less than about 180 sec, and where the processor applies the assay input signal during an assay period of less than about 180 sec.

15. The biosensor of claim 11, where the processor applies the polling input signal during a polling period in the range of about 0.1 sec through about 10 sec, and where the processor applies the assay input signal during an assay period in the range of about 1 sec through about 100 sec.

16. The biosensor of claim 11,

where the processor applies 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, a polling pulse interval of about 125 ms, and a potential of about 400 mV;

and

where the processor applies 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, an assay pulse interval of about 1.5sec, a first pulse with a potential of about 400 mV, and at least one other pulse with a potential of about 200 mV.

17. The biosensor of claim 11, where the processor further comprises comparator circuitry and the processor applies the assay input signal when a polling output signal is greater than or equal to a polling threshold of about 250 nA.

18. The biosensor of claim 11, where the processor directs a signal generator to provide the assay input signal to a sensor interface.

19. The biosensor of claim 18, where the sensor interface applies the assay input signal to the sample through electrodes in the sample interface.

20. The biosensor of claim 11, where the processor directs a signal generator to provide the polling input signal to a sensor interface.

21. The biosensor of claim 1, where a normal output signal within the at least one control limit provides an accurate and/or precise analysis of the biological fluid and where an abnormal 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.

22. The biosensor of claim 1, where the sample of the biological fluid is whole blood, where the processor separates normalized current values of the output signal in response to underlying current profiles, and where the processor selects the at least one control limit to include an acceptable variation of the normalized current values about a mean using statistical techniques.

23. A method of operating a biosensor system for determining an analyte concentration in a biological fluid sample, the biosensor system including a measurement device and a test sensor, the measurement device having a processor, the measurement device being in electrical or optical communication with a reservoir of the test sensor, the method comprising:

applying, by the processor of the measurement device, a pulsed electrical input signal to a sample of a biological fluid located in the reservoir of the test sensor, the pulses of the input signal separated by relaxations where the signal is off;

generating, by the processor of the measurement device, 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, by the processor of the measurement device, the output signal from the redox reaction of the analyte in the sample;

normalizing, by the processor of the measurement device, 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, the normalized output signal being indicative of the analyte concentration in the sample;

comparing, by the processor of the measurement device, a 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 at least one transition of the output signal from normal to abnormal;

generating, by the processor of the measurement device, an error signal when the normalized output signal is not within the at least one control limit, the error signal being indicative of an error in analysis of the analyte concentration in the sample;

calculating, by the processor of the measurement device, a ratio of a first normalized current value from one of the pulses to a second normalized current value from another one of the pulses; and

where the analyte undergoes a redox reaction when the input signal is applied to the sample.