System error compensation of analyte concentration determinations

• US 10,330,629 B2
• Filed: 03/11/2014
• Issued: 06/25/2019
• Est. Priority Date: 03/14/2013
• Status: Active Grant

• Current Assignee: Ascensia Diabetes Care Holdings AG (PHC Holdings Corporation)
• Original Assignee: Ascensia Diabetes Care Holdings AG (PHC Holdings Corporation)
• Inventors: Wu, Huan-Ping
• Primary Examiner(s): Vanni, G Steven
• Application Number:
  US14/774,684
• Publication Number:
  US 20160025673A1
• Time in Patent Office: 1,932 Days
• Field of Search: None
• CPC Class Codes: G01N 27/3274 Corrective measures, e.g. error detection, compensation for temperature or hematocrit, calibration coding of calibration information G01N33/48771
• CPC Class Codes: G01N 33/723 Glycosylated haemoglobin

Abstract

During analyte analysis, errors may be introduced into an analysis by both the biosensor system used to perform the analysis and by errors in the output signal measured by the measurement device of the biosensor. For a reference sample, system error may be determined through the determination of relative error. However, during an analysis of a test sample with the measurement device of the biosensor system, true relative error cannot be known. A pseudo-reference concentration determined during the analysis may be used as a substitute for true relative error. The present invention introduces the determination of a pseudo-reference concentration determined during the analysis as a substitute for the true relative error and uses an anchor parameter to compensate for the system error in the analysis-determined pseudo-reference concentration.

Claims

1. A method of operating a biosensor system for determining an analyte concentration in a sample, the method comprising:

providing a biosensor system in the form of an analytical instrument including

a measurement device having electrical circuitry communicatively coupled to a processor, a storage medium, a signal generator, and a sensor interface, the processor having instructions and data stored in the storage medium, and

a test sensor having a base and a sample interface, the base forming a reservoir and a channel with an opening, the reservoir being in electrical or optical communication with the measurement device;

receiving a biological fluid sample in the opening of the reservoir, the biological fluid sample flowing through the channel to fill at least in part the reservoir of the test sensor, the biological fluid sample including the analyte;

in response to receiving the biological fluid sample in the reservoir, generating an input signal, by the processor, from the signal generator;

transmitting the input signal by the sensor interface to the sample interface for applying the input signal to the biological fluid sample;

in response to the input signal and a concentration of an analyte in the biological fluid sample, generating and measuring, by the processor, at least one analyte responsive output signal from the test sensor, the at least one analyte responsive output signal being one or more of an electrical output signal generated by a redox reaction or a light-generated output signal in response to a light-identifiable species;

determining, by the processor, a pseudo-reference concentration value from the at least one analyte responsive output signal, the pseudo-reference concentration value being a substitute for true relative error;

determining, by the processor, at least one anchor parameter in response to the pseudo-reference concentration value, the at least one anchor parameter compensating for system error and being determined by subtracting the pseudo-reference concentration value from an initial analyte concentration determined with the measurement device, and then, dividing by the pseudo-reference concentration value;

incorporating, by the processor, the at least one anchor parameter into a compensation relationship;

determining, by the processor, a final compensated analyte concentration of the biological fluid sample in response to the compensation relationship; and

outputting, by the processor, the final compensated analyte concentration to one or more of a display, a remote receiver, or a storage medium.

2. The method of claim 1, further comprising:

measuring at least one extraneous stimulus responsive output signal from the biological fluid sample;

selecting a sample analyte concentration value as the pseudo-reference concentration value, where the sample analyte concentration value for multiple analyses is on average closer to an actual analyte concentration of the biological fluid sample than would be independently determined from the one analyte responsive output signal; and

determining the pseudo-reference concentration value in response to the one analyte responsive output signal and primary compensation

determining the at least one anchor parameter in response to the pseudo-reference concentration value and one analyte responsive output signal, where the at least one anchor parameter is a concentration anchor parameter=(the initial analyte concentration determined from the one analyte responsive output signal without compensation the pseudo-reference concentration value determined with compensation)/the pseudo-reference concentration value determined with compensation.

3. The method of claim 1,

where the measuring at least one analyte responsive output signal comprises measuring at least two analyte responsive output signals from the biological fluid sample and

where the determining a pseudo-reference concentration value comprises selecting a sample analyte concentration value as the pseudo-reference concentration value, where the sample analyte concentration value for multiple analyses is on average closer to an actual analyte concentration of the biological fluid sample than would be independently determined from the at least two analyte responsive output signals.

4. The method of claim 3, where the determining a pseudo-reference concentration value comprises:

determining the initial analyte concentration of each of the at least two analyte responsive output signals and

averaging the initial analyte concentrations.

5. The method of claim 3, where the determining at least one anchor parameter comprises:

determining a first anchor parameter in response to a first normalized output signal value and a pseudo-reference signal, where the first normalized output signal value is responsive to a first analyte response output signal and a normalizing relationship;

determining a second anchor parameter in response to a second normalized output signal value and the pseudo-reference signal, where the second normalized output signal value is responsive to a second analyte response output signal and the normalizing; and

determining the pseudo-reference signal in response to the pseudo-reference concentration value and a normalized reference correlation.

6. The method of claim 5,

where the first anchor parameter comprises a first signal anchor parameter=(NR_OSV1−

NR_Pseudo)/NR_Pseudo, where NR_OSV1 is the first normalized output signal value and NR_Pseudo is the pseudo-reference signal and

where the second anchor parameter comprises a second signal anchor parameter=(NR_OSV2−

NR_Pseudo)/NR_Pseudo, where NR_OSV2 is the second normalized output signal value and NR_Pseudo is the pseudo-reference signal value.

7. The method of claim 5, further comprising:

determining the normalizing relationship between at least two analyte responsive output signals and at least two quantified extraneous stimulus values;

determining the at least two quantified extraneous stimulus values from the at least one extraneous stimulus responsive output signal;

measuring at least one extraneous stimulus responsive output signal from at least one reference biological fluid sample;

determining a reference correlation between a reference sample analyte concentration of the at least one reference biological fluid sample and at least two analyte responsive output signals;

determining the at least one normalized reference correlation between at least two normalized analyte responsive output signals and the reference sample analyte concentration; and

determining the at least two normalized analyte responsive output signals from the at least two analyte responsive output signals and the normalizing value.

8. The method of claim 7, where determining the normalizing relationship comprises applying a normalizing relationship regression technique to the at least two analyte responsive output signals and the at least two quantified extraneous stimulus values at a single selected analyte concentration, and where determining the at least one normalized reference correlation comprises applying a normalized reference correlation regression technique to the at least two normalized analyte responsive output signals and the at least one reference sample analyte concentration.

9. The method of claim 7, further comprising:

determining at least two second quantified extraneous stimulus values from the at least one extraneous stimulus responsive output signal;

determining a second normalizing relationship between the at least two normalized analyte responsive output signals and the at least two second quantified extraneous stimulus values;

determining at least two second normalized analyte responsive output signals from the at least two normalized analyte responsive output signals and a second normalizing value; and

determining a second normalized reference correlation between the at least two second normalized analyte responsive output signals and the at least one reference sample analyte concentration.

10. The method of claim 9, where the determining a second normalizing relationship comprises applying a second normalizing relationship regression technique to the at least two normalized analyte responsive output signals and the at least two second quantified extraneous stimulus values at a single selected analyte concentration, and where determining a second normalized reference correlation comprises applying a second normalized reference correlation regression technique to the at least two second normalized analyte responsive output signals and the at least one reference sample analyte concentration.

11. A biosensor system for determining an analyte concentration in a biological fluid sample, the biosensor system being an optical system or an electrochemical system, the biosensor system comprising:

a test sensor having a base and a sample interface, the base forming a reservoir and a channel with an opening, the opening being configured to receive a biological fluid sample and to allow the biological fluid sample to flow through the channel to fill at least in part the reservoir;

a measurement device in electrical or optical communication with the reservoir, the measurement device having electrical circuitry communicatively coupled to a processor, a storage medium, a signal generator, and a sensor interface, the processor having instructions and data stored in the storage medium, the instructions configured such that when executed by the processor the system is enabled so that;

in response to receiving the biological fluid sample in the reservoir, the signal generator applies an electrical or optical input signal to the sensor interface,

the input signal is transmitted by the sensor interface to the sample interface for applying the input signal to the biological fluid sample,

in response to the input signal and to the concentration of the analyte in the biological fluid sample, the processor generates and measures at least one analyte responsive output signal, the output signal being one or more of a light-generated output signal in response to a light-identifiable species and an electrical output signal generated by a redox reaction,

where the processor is capable of measuring at least one analyte responsive output signal,

the processor determines a pseudo-reference concentration value from the at least one analyte responsive output signal, where a pseudo-reference concentration value is a substitute for true relative error,

the processor determines at least one anchor parameter in response to the pseudo-reference concentration value, the at least one anchor parameter compensating for system error and being determined by subtracting the pseudo-reference concentration value from an initial analyte concentration determined with the measurement device, and then, dividing by the pseudo-reference concentration value,

the processor incorporates the at least one anchor parameter into a compensation relationship,

the processor determines a final compensated analyte concentration of the biological fluid sample in response to the compensation relationship, and

the processor outputs the final compensated analyte concentration to one or more of a display, a remote receiver, or a storage medium.

12. The biosensor system of claim 11, wherein the system is further enabled so that:

the processor measures at least one extraneous stimulus responsive output signal and

the processor determines a pseudo-reference concentration value that comprises selecting a sample analyte concentration value as the pseudo-reference concentration value, the sample analyte concentration value for multiple analyses being on average closer to an actual analyte concentration of the biological fluid sample than would be independently determined from the one analyte responsive output signal.

13. The biosensor system of claim 12, wherein the system is further enabled so that the processor determines the pseudo-reference concentration value in response to the one analyte responsive output signal and primary compensation.

14. The biosensor system of claim 13, wherein the system is further enabled so that the processor determines the at least one anchor parameter in response to the pseudo-reference concentration value and the one analyte responsive output signal.

15. The biosensor system of claim 14, where the at least one anchor parameter is a concentration anchor parameter=(the initial analyte concentration determined from the one analyte responsive output signal without compensation the pseudo-reference concentration value determined with compensation)/the pseudo-reference concentration value determined with compensation.