# US 12,216,074 B2 · Biosensors and methods for determining analyte concentration in the kinetic potential region of redox mediators

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- Number: US 12,216,074 B2
- Document ID: US12216074B2
- Status: Granted
- Kind: B2
- Application number: 17/956,185
- Filed: 2022-09-29
- Published: 2024-03-21
- Granted: 2025-02-04
- Earliest claimed: 2021-10-01
- Assignees: Pacific Diabetes Technologies, Inc.
- Applicants: Pacific Diabetes Technologies, Inc.
- Inventors: Thomas Seidl; William Kenneth Ward; Huan-Ping Wu
- Web page: https://patentgrep.com/patent/US12216074B2

## CPC

- G01N 27/26: by investigating electrochemical variables; by using electrolysis or electrophoresis
- A61B 5/14532: {for measuring glucose, e.g. by tissue impedance measurement}
- A61B 5/14865: {invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors}
- A61B 5/1495: Calibrating or testing of in-vivo probes
- G01N 27/3274: {Corrective measures, e.g. error detection, compensation for temperature or hematocrit, calibration (coding of calibration information G01N33/48771)}
- A61B 5/1486: using enzyme electrodes, e.g. with immobilised oxidase
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)
- A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D)

## Abstract

Methods and devices useful for determining the analyte concentration of a sample using output currents obtained from an input potential in the kinetic potential region of a redox mediator are disclosed. Preferably, the input potential used to generate the output currents from the kinetic potential region of the redox mediator is continually increasing with time after initiating the analysis. A method of selecting an initial input potential within the kinetic potential region of a redox mediator based on the sensitivity of an individual or batch of subcutaneously insertable test sensors also is described. A method of selecting an analysis input potential within the kinetic potential region of redox mediator based on the sensitivity of an individual subcutaneously inserted test sensor also is described where the analysis input potential is increased with insertion time.

## Claims

### Claim 1

A method for determining an analyte concentration in a sample, the method comprising:
applying a first and second calibration input potentials to a subcutaneously inserted test sensor, where the first and second calibration input potentials are within a kinetic potential region of a redox mediator of the test subcutaneously inserted test sensor;
measuring output currents responsive to the first and the second calibration input potentials from the subcutaneously inserted test sensor;
determining a regression sensitivity relationship from the measured output currents responsive to the first and the second calibration input potentials;
determining a first analysis input potential within the kinetic potential region of the redox mediator from the regression sensitivity relationship;
applying the first analysis input potential to the subcutaneously inserted test sensor;
modifying a first redox state to a second redox state of the redox mediator, where a concentration of the first redox state of the redox mediator is responsive to an analyte concentration in a sample;
measuring output currents responsive to the first analysis input potential from the subcutaneously inserted test sensor;
determining the analyte concentration of the sample in response to the measured output currents responsive to the first analysis input potential; and
reporting the determined analyte concentration to a user.

### Claim 2 (depends on 1)

The method of claim 1, further comprising obtaining predetermined calibration information before the applying the first and second calibration input potentials to the subcutaneously inserted test sensor.

### Claim 3 (depends on 2)

The method of claim 2, where the first analysis input potential is responsive to a sensitivity of the subcutaneously inserted test sensor and to a manufactured sensitivity of multiple not-subcutaneously inserted test sensors.

### Claim 4 (depends on 2)

The method of claim 2, where the predetermined calibration information includes an input potential ramping routine, an initial input potential, and the first and second calibration input potential values altered for a specific lot of test sensors.

### Claim 5 (depends on 1)

The method of claim 1, where the first analysis input potential is responsive to a sensitivity of the subcutaneously inserted test sensor.

### Claim 6 (depends on 5)

The method of claim 5, where the sensitivity arises from subcutaneous insertion and a manufactured sensitivity of the test sensor.

### Claim 7 (depends on 1)

The method of claim 1, where the determining the regression sensitivity relationship comprises use of a reference analyte concentration of the sample.

### Claim 8 (depends on 7)

The method of claim 7, where the determining the regression sensitivity relationship includes modifying the measured output currents responsive to the first and second calibration input potentials by the reference analyte concentration of the sample.

### Claim 9 (depends on 1)

The method of claim 1, where the regression sensitivity relationship comprises a slope and an intercept.

### Claim 10 (depends on 9)

The method of claim 9, where the determining the analysis input potential comprises using a relationship: the first analysis input potential=the slope*a selected sensitivity+the intercept.

### Claim 11 (depends on 1)

The method of claim 1, where the determining the analyte concentration of the sample comprises correlating the measured output currents with the analyte concentration of the sample using a conversion function.

### Claim 12 (depends on 1)

The method of claim 1, further comprising modifying the first analysis input potential with an input potential ramping routine.

### Claim 13 (depends on 1)

The method of claim 1, further comprising determining a second analysis input potential, measuring output currents responsive to the second analysis input potential, and determining the analyte concentration of the sample in response to the measured output currents responsive to the second analysis input potential.

### Claim 14 (depends on 1)

The method of claim 1, where the first analysis input potential continually increases after the application of the first analysis input potential to the subcutaneously inserted test sensor.

### Claim 15 (depends on 1)

The method of claim 1, where the measured output currents responsive to the first analysis input potential are substantially linear.

### Claim 16 (depends on 1)

The method of claim 1, where the output currents measured in response to the first analysis input potential are accurately correlatable to the analyte concentration of the sample within 30 minutes to 3 hours of subcutaneously inserting the test sensor into a subject.

### Claim 17 (depends on 1)

The method of claim 1, where the redox mediator is osmium-complex based.

### Claim 18 (depends on 1)

The method of claim 1, where the first analysis input potential is a lower potential than a plateau oxidation potential of the redox mediator.

### Claim 19 (depends on 1)

The method of claim 1, where the first analysis input potential is determined within 0.1 to 0.3 hours of subcutaneously inserting the test sensor into a subject.

### Claim 20 (depends on 1)

The method of claim 1, where movement of the analyte to working and counter electrodes of the subcutaneously inserted test sensor is non-diffusion-limited.

### Claim 21 (depends on 1)

The method of claim 1, where the output currents responsive to the first analysis input potential change in response to changes in the first analysis input potential.

### Claim 22 (depends on 1)

The method of claim 1, where the first and second calibration input potentials are applied to a subcutaneously inserted test sensor for 1 minute to 30 minutes after subcutaneously inserting the test sensor into a subject.

### Claim 23

A method of determining an initial input potential for a test sensor based on the manufactured sensitivity of the test sensor, for performing an analysis of a sample with the test sensor, the method comprising:
applying a first and second calibration input potentials to a test sensor contacting a sample, where the first and second calibration input potentials are within a kinetic potential region of a redox mediator of the test sensor;
measuring output currents responsive to the first and the second calibration input potentials from the test sensor;
determining a regression sensitivity relationship from the measured output currents responsive to the first and the second calibration input potentials using a known laboratory analyte concentration or a reference analyte concentration of the sample by modifying the measured output currents responsive to the first and the second calibration input potentials with the known laboratory analyte concentration or the reference analyte concentration of the sample;
determining an initial input potential by multiplying a slope from the regression sensitivity relationship by a selected sensitivity and combining with an intercept from the regression sensitivity relationship.

### Claim 24 (depends on 23)

The method of claim 23, where the initial input potential is incorporated into predetermined calibration information for the test sensor.

### Claim 25

A method of determining an initial input potential for a test sensor based on the manufactured sensitivity of the test sensor, for performing an analysis of a sample with the test sensor, the method comprising:
applying a first and second calibration input potentials to multiple test sensors contacting a sample, where the first and the second calibration input potentials are within a kinetic potential region of a redox mediator of the test sensor;
measuring output currents responsive to the first and the second calibration input potentials from the multiple test sensors;
determining a first calibration input potential regression relationship and a second calibration input potential regression relationship from the output currents measured from the multiple test sensors and a known laboratory analyte concentration or a reference analyte concentration to obtain a first calibration input potential change rate and a second calibration input potential change rate;
determining pair point relationship for a single test sensor from a rising slope (RS) value of the single test sensor, a selected sensitivity, and the intercept of the first and second calibration input potential regression relationships;
determining a change rate relationship from the first and second calibration input potentials and the first and second calibration input potential change rates; and
determining an initial input potential for the test sensor from the change rate relationship and a single test sensor change rate determined from the pair point relationship.

### Claim 26 (depends on 25)

The method of claim 25, where the initial input potential is incorporated into predetermined calibration information for the test sensor.

### Claim 27

An analyte measurement device, comprising:
a processor in electrical communication with a signal generator and a storage medium,
where the processor is configured to measure output currents responsive to input potentials,
where the signal generator is configured to provide the input potentials to working and counter electrodes of a test sensor and transferring output currents responsive to the input potentials from the test sensor to the processor;
where the processor is configured to instruct the signal generator to apply a first and second calibration input potentials to the test sensor, where the first and second calibration input potentials are within a kinetic potential region of a redox mediator of the test sensor;
where the processor is configured to measure output currents responsive to the first and the second calibration input potentials;
where the processor is configured to determine a regression sensitivity relationship from the measured output currents responsive to the first and the second calibration input potentials;
where the processor is configured to determine a first analysis input potential within the kinetic potential region of the redox mediator from the regression sensitivity relationship;
where the processor is configured to instruct the signal generator to apply the first analysis input potential to the test sensor;
where the processor is configured to measure output currents responsive to the first analysis input potential from the test sensor;
where the processor is configured to determine the analyte concentration of a sample in response to the measured output currents responsive to the first analysis input potential; and
where the processor is configured to report the determined analyte concentration to a user.

### Claim 28 (depends on 27)

The analyte measurement device of claim 27, where the processor is configured to obtain predetermined calibration information and store the predetermined calibration information in the storage medium.

### Claim 29 (depends on 28)

The analyte measurement device of claim 28, where the first analysis input potential is responsive to a sensitivity of the test sensor and to a manufactured sensitivity of multiple test sensors.

### Claim 30 (depends on 28)

The analyte measurement device of claim 28, where the predetermined calibration information includes an input potential ramping routine, an initial input potential, and the first and second calibration input potential values altered for a specific lot of test sensors.

### Claim 31 (depends on 27)

The analyte measurement device of claim 27, where the first analysis input potential is responsive to a sensitivity of the subcutaneously inserted test sensor.

### Claim 32 (depends on 27)

The analyte measurement device of claim 27, where the determining the regression sensitivity relationship comprises use of a reference analyte concentration of the sample supplied by the user.

### Claim 33 (depends on 32)

The analyte measurement device of claim 32, where the determining the regression sensitivity relationship includes modifying the measured output currents responsive to the first and second calibration input potentials by the reference analyte concentration of the sample.

### Claim 34 (depends on 27)

The analyte measurement device of claim 27, where the regression sensitivity relationship includes a slope and an intercept.

### Claim 35 (depends on 34)

The analyte measurement device of claim 34, where the determining the analysis input potential comprises using a relationship stored in the storage medium as follows: the first analysis input potential=the slope*a selected sensitivity+the intercept.

### Claim 36 (depends on 27)

The analyte measurement device of claim 27, where the determining the analyte concentration of the sample comprises correlating the measured output currents with the analyte concentration of the sample using a conversion function stored in the storage medium.

### Claim 37 (depends on 27)

The analyte measurement device of claim 27, where the processor is configured to modify the first analysis input potential with an input potential ramping routine stored in the storage medium.

### Claim 38 (depends on 27)

The analyte measurement device of claim 27, where the processor is configured to determine a second analysis input potential, to measure output currents responsive to the second analysis input potential, and to determine the analyte concentration of the sample in response to the measured output currents responsive to the second analysis input potential.

### Claim 39 (depends on 27)

The analyte measurement device of claim 27, where the processor is configured to continually increase the first analysis input potential after the applying the first analysis input potential to the test sensor.

### Claim 40 (depends on 27)

The analyte measurement device of claim 27, where the output currents responsive to the first analysis input potential measured by the processor are substantially linear.

### Claim 41 (depends on 27)

The analyte measurement device of claim 27, where the processor is configured to accurately correlate the output currents measured by the processor in response to the first analysis input potential to the analyte concentration within 30 minutes to 3 hours of subcutaneous insertion of the test sensor into a subject.

### Claim 42 (depends on 27)

The analyte measurement device of claim 27, where the first analysis input potential is a lower potential than a plateau oxidation potential of the redox mediator.

### Claim 43 (depends on 27)

The analyte measurement device of claim 27, where the processor is configured to determine the first analysis input potential within 0.1 to 0.3 hours of subcutaneous insertion of the test sensor into a subject.

### Claim 44 (depends on 27)

The analyte measurement device of claim 27, where the processor is configured to apply the first and the second calibration input potentials to the test sensor for 1 minute to 30 minutes after subcutaneous insertion of the test sensor into a subject.

### Claim 45

A biosensor system for determining an analyte concentration in a sample, comprising:
a test sensor comprising working and counter electrodes and a redox mediator;
a measurement device comprising a processor in electrical communication with a signal generator and a storage medium, where the working and the counter electrodes are in electrical communication with the signal generator;
where the processor is configured to measure output currents responsive to input potentials from the test sensor,
where the signal generator is configured to provide the input potentials to the working and the counter electrodes and transferring output currents responsive to the input potentials from the working and the counter electrodes to the processor;
where the processor is configured to instruct the signal generator to apply a first and second calibration input potentials to the working and the counter electrodes, where the first and second calibration input potentials are within a kinetic potential region of the redox mediator;
where the processor is configured to measure output currents responsive to the first and the second calibration input potentials;
where the processor is configured to determine a regression sensitivity relationship from the measured output currents responsive to the first and the second calibration input potentials;
where the processor is configured to determine a first analysis input potential within the kinetic potential region of the redox mediator from the regression sensitivity relationship;
where the processor is configured to instruct the signal generator to apply the first analysis input potential to the working and the counter electrodes;
where the processor is configured to measure output currents responsive to the first analysis input potential from the working and the counter electrodes;
where the processor is configured to determine the analyte concentration of a sample in response to the measured output currents responsive to the first analysis input potential; and
where the processor is configured to report the determined analyte concentration to a user.

### Claim 46 (depends on 45)

The biosensor system of claim 45, where the processor is configured to obtain predetermined calibration information and store the predetermined calibration information in the storage medium.

### Claim 47 (depends on 46)

The biosensor system of claim 46, where the first analysis input potential is responsive to a sensitivity of the test sensor and to a manufactured sensitivity of multiple test sensors.

### Claim 48 (depends on 46)

The biosensor system of claim 46, where the predetermined calibration information includes an input potential ramping routine, an initial input potential, and the first and second calibration input potential values altered for a specific lot of test sensors.

### Claim 49 (depends on 45)

The biosensor system of claim 45, where the first analysis input potential is responsive to a sensitivity of the subcutaneously inserted test sensor.

### Claim 50 (depends on 45)

The biosensor system of claim 45, where the determining the regression sensitivity relationship comprises use of a reference analyte concentration of the sample supplied by the user.

### Claim 51 (depends on 50)

The biosensor system of claim 50, where the determining the regression sensitivity relationship includes modifying the measured output currents responsive to the first and second calibration input potentials by the reference analyte concentration of the sample.

### Claim 52 (depends on 45)

The biosensor system of claim 45, where the regression sensitivity relationship includes a slope and an intercept.

### Claim 53 (depends on 52)

The biosensor system of claim 52, where the determining the analysis input potential comprises using a relationship stored in the storage medium as follows: the first analysis input potential=the slope*a selected sensitivity+the intercept.

### Claim 54 (depends on 45)

The biosensor system of claim 45, where the determining the analyte concentration of the sample comprises correlating the measured output currents with the analyte concentration of the sample using a conversion function stored in the storage medium.

### Claim 55 (depends on 45)

The biosensor system of claim 45, where the processor is configured to modify the first analysis input potential with an input potential ramping routine stored in the storage medium.

### Claim 56 (depends on 45)

The biosensor system of claim 45, where the processor is configured to determine a second analysis input potential, to measure output currents responsive to the second analysis input potential, and to determine the analyte concentration of the sample in response to the measured output currents responsive to the second analysis input potential.

### Claim 57 (depends on 45)

The biosensor system of claim 45, where the processor is configured to continually increase the first analysis input potential after the applying the first analysis input potential to the test sensor.

### Claim 58 (depends on 45)

The biosensor system of claim 45, where the output currents responsive to the first analysis input potential measured by the processor are substantially linear.

### Claim 59 (depends on 45)

The biosensor system of claim 45, where the processor is configured to accurately correlate the output currents measured by the processor in response to the first analysis input potential to the analyte concentration of the sample within 30 minutes to 3 hours of subcutaneously inserting the test sensor into a subject.

### Claim 60 (depends on 45)

The biosensor system of claim 45, where the first analysis input potential is a lower potential than a plateau oxidation potential of the redox mediator.

### Claim 61 (depends on 45)

The biosensor system of claim 45, where the processor is configured to determine the first analysis input potential within 0.1 to 0.3 hours of subcutaneously inserting the test sensor into a subject.

### Claim 62 (depends on 45)

The biosensor system of claim 45, where the processor is configured to apply the first and the second calibration input potentials to the working and the counter electrodes for 1 minute to 30 minutes after subcutaneously inserting the test sensor into a subject.