METHOD AND DEVICE FOR DETERMINING A CONCENTRATION OF AT LEAST ONE ANALYTE

• US 20190310221A1
• Filed: 06/14/2019
• Published: 10/10/2019
• Est. Priority Date: 12/21/2016
• Status: Active Grant

• Current Assignee: Roche Diagnostics Operations Incorporated (Roche Holding AG)
• Original Assignee: Roche Diagnostics Operations Incorporated (Roche Holding AG)
• Inventors: Marquant, Michael, Evgin, Samuel, Klein, Melanie
• Granted Patent: US 11,125,712 B2
• Time in Patent Office: Days
• 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

A method for determining a concentration of at least one analyte in bodily fluid, comprising: a signal generation step, wherein an excitation voltage signal is generated by a signal generator, wherein the excitation voltage signal comprises a poly frequent alternating current (AC) voltage and a direct current (DC) voltage profile, wherein the poly frequent AC voltage comprises at least two frequencies; a signal application step, wherein the excitation voltage signal is applied to at least two measurement electrodes; a measurement step, wherein a response is measured by using the measurement electrodes; an evaluation step, wherein an AC current response for each frequency and a DC current response are evaluated from the response; a determination step, wherein the concentration of the analyte is determined from the DC current response and from one or both of the phase and impedance information by using at least one predetermined relationship.

Claims

1. A method for determining a concentration of at least one analyte in bodily fluid, the method comprising the following steps:

at least one signal generation step, wherein at least one excitation voltage signal is generated by at least one signal generator device, wherein the excitation voltage signal comprises at least one poly frequent alternating current (AC) voltage and at least one direct current (DC) voltage profile, wherein the poly frequent AC voltage comprises at least two frequencies;

at least one signal application step, wherein the excitation voltage signal is applied to at least two measurement electrodes, which are in contact with the bodily fluid and which are adapted to determine the analyte electrically or electrochemically;

at least one measurement step, wherein a response is measured by using the measurement electrodes;

at least one evaluation step, wherein an AC current response for each frequency and a DC current response are evaluated from the response by at least one evaluation device, and wherein for each frequency at least one phase information and at least one impedance information is evaluated from the AC current response by the evaluation device;

at least one determination step, wherein the concentration of the analyte is determined from the DC current response and from one or both of the phase information and impedance information by using at least one predetermined relationship,

wherein the AC voltage and DC profile are superimposed to form the excitation voltage signal.

2. The method according to claim 1, wherein the predetermined relationship is

bG=Σ

_i=1ⁿa_iDC_ie<sup>Σ

m=1fbmiYmi+cmiPmi</sup>,

wherein bG is the determined analyte concentration, i denotes the number of measurement time points, wherein i, n, f and m are natural integer numbers, m denotes the number of frequencies, a_i, b_i, c_i are weighting coefficients, Ym_j are admittance values from AC response at different frequencies at time points, Pm_j are phase angle values from AC response at different frequencies at time points and DC_i are DC response values at selected DC response time points.

3. The method according to claim 1, wherein the predetermined relationship is

4. The method according to claim 3, wherein the predetermined relationship is,

5. The method according to claim 3, wherein the predetermined relationship is

6. The method according to claim 1, wherein the method comprises determining a predetermined relationship between the concentration of the analyte and the DC current response, the phase information and impedance information.

7. The method according to claim 1, wherein in the determination step the concentration of the analyte is determined in consideration of interference effects and production tolerances.

8. The method according to claim 1, wherein the AC voltage has a magnitude less than 30 mV rms.

9. The method according to claim 1, wherein the method further comprises at least one selection step, wherein in the selection step from the measurement time points at least one DC time point is selected, wherein the DC time point is a time point at which the DC response current is used in the determination step.

10. The method according to claim 1, wherein the DC voltage profile comprises a time profile, wherein DC voltage profile is selected from the group consisting of:

a voltammetric voltage profile;

an amperometric voltage profile.

11. The method according to claim 1, wherein in the evaluation step the AC current response and the DC current response are separated using at least one two-way analog electronic filter, which splits the signals between about 100 Hz and 500 Hz, wherein below 100 Hz the response is analyzed as DC and above 500 Hz it is analyzed as AC.

12. The method according to claim 1, wherein the predetermined relationship is one or more of selected, determined and verified by mathematical methods selected from the group consisting of multivariate analysis, multilinear principal component analysis, neuronal nets, moving mesh, lasso method, boosted random forest and bootstrapping, on at least one training data set.

13. The method according to claim 1, wherein the method comprises at least one fail safe step, wherein the fail safe step comprises determining if the analyte concentration is valid within predetermined limits.

14. The method according to claim 1, wherein the method comprises a sample application step, wherein a sample of bodily fluid is brought in contact with the measurement electrodes.

15. An analytical device for determining a concentration of at least one analyte in bodily fluid, the analytical device comprising:

at least one signal generator device adapted to generate at least one excitation voltage signal, wherein the excitation voltage signal comprises at least one poly frequent alternating current (AC) voltage and at least one direct current (DC) voltage profile, wherein the poly frequent AC voltage comprises at least two frequencies;

at least one measurement unit, wherein the measurement unit is adapted to receive a response,

at least one evaluation device adapted to evaluate an AC current response for each frequency and a DC current response from the response, wherein the evaluation device is adapted to evaluate for each frequency at least one phase information and at least one impedance information is evaluated from the AC current response,

wherein the evaluation device is adapted to determine a concentration of the analyte from the DC current response and from one or both of the phase information and impedance information by using at least one predetermined relationship,

wherein the AC voltage and DC profile are superimposed to form the excitation voltage signal.

16. The analytical device according to the claim 15, wherein the signal generator is adapted to apply the excitation voltage signal to at least two measurement electrodes of at least one test element.

17. A test element analysis system for determining a concentration of at least one analyte in bodily fluid, comprising:

at least one analytical device according to claim 15;

at least one test element having at least one measuring zone capable of performing at least one change being characteristic for the analyte, wherein the test element comprises at least two measuring electrodes.