SYSTEM AND METHOD FOR DIAGNOSING SENSOR PERFORMANCE USING ANALYTE-INDEPENDENT RATIOMETRIC SIGNALS

• US 20140141524A1
• Filed: 03/14/2013
• Published: 05/22/2014
• Est. Priority Date: 11/20/2012
• Status: Active Grant

• Current Assignee: Becton, Dickinson & Co
• Original Assignee: Becton, Dickinson & Co
• Inventors: Keith, Steven
• Granted Patent: US 10,466,247 B2
• Time in Patent Office: Days
• US Class Current: 436/501
• CPC Class Codes: G01N 21/6428 Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" in vivo A61B5/00; immunoassay G01N33/53
• CPC Class Codes: G01N 33/52 Use of compounds or compositions for colorimetric, spectrophotometric or fluorometric investigation, e.g. use of reagent paper and including single- and multilayer analytical elements immunological elements G01N33/54386; involving labelled immunochemicals G01N33/58; for haemoglobin or occult blood G01N33/72
• CPC Class Codes: G01N 33/66 involving blood sugars, e.g. galactose

Abstract

A system and method are provided for utilizing radiometric fluorescence detection to determine a glucose independent concentration value when measuring frequency bands that do not contain the system isosbestic point. Preferably two bands are chosen such that a first band is below the system isosbestic point, and a second band is above the system isosbestic point, and both points are sufficiently far from the frequency endpoints to maximize the signal to noise ratio.

Claims

1. A method of performing a diagnostic test on an analyte sensor, comprising the steps of:

introducing matrix suspended analyte binding protein to an analyte environment, said binding protein labeled with a dye fluorescing with an intensity spectrum related to a concentration of said analyte concentration in said environment;

measuring a first fluorescent intensity at a first frequency component that is higher than an isosbestic frequency of the dye;

measuring a second fluorescent intensity at a second frequency component that is lower than the isosbestic frequency;

determining a GIIC value based on the first and second fluorescent intensities;

diagnosing a performance of said analyte sensor based on said determination.

2. The method of claim 1, wherein the analyte binding protein is a glucose binding protein.

3. The method of claim 1, wherein said analyte is glucose.

4. The method of claim 1, wherein a ratio between the first frequency component and the second frequency component for the dye is defined by:

R=(R0+Rinf([G]/KD))/(1+[G]/KD)

where

[G] is the analyte concentration;

R is the ratio at a given analyte concentration;

R0 is the ratio of spectral bands at zero analyte concentration;

Rinf is the ratio of spectral bands at infinite (saturating) analyte concentration; and

KD is an apparent dissociation constant for the system.

5. The method of claim 4, wherein the analyte is glucose, and [G] is the glucose concentration.

6. The method of claim 4, wherein a glucose independent intensity is calculated according to the following equation:

GII=(KDg/KDb−

1)*Fb*Fg+Fb*(Fginf−

(KDg/KDb)*Fg0)+Fg(Fb0−

(KDg/KDb)*Fbinf)

where

GII is the glucose independent intensity;

Fb is the measured intensity of the first frequency component;

Fg is the measured intensity of the second frequency component;

KDg is the dissociation constant determined when using only the second frequency component;

KDb is the dissociation constant determined when using only the first frequency component;

Fginf is the intensity of the second frequency component at saturated concentration;

Fg0 is the intensity of the second frequency component at zero concentration;

Fbinf is the intensity of the first frequency component at saturated concentration; and

Fb0 is the intensity of the first frequency component at zero concentration.

7. The method of claim 1, wherein a computing architecture that processes a raw sensor signal also calculates analyte concentration.

8. The method of claim 1, wherein the first frequency component and the second frequency component are selected to be far from the isosbestic frequency but closer than frequencies at which the signal to noise ratio drops below 10% of the maximum signal to noise ratio.

9. The method of claim 1, wherein the first fluorescent intensity is generated by a first dye and the second fluorescent intensity is generated by a second dye.

10. A system for performing a diagnostic test on an analyte sensor, comprising:

a matrix suspended analyte binding protein element adapted for introduction to an analyte environment;

a fluorescence intensity measuring device for measuring fluorescence intensity at first and second respective frequencies, the first frequency being higher than an isosbestic frequency of the dye, and the second frequency being lower than the isosbestic frequency of the dye;

a processor for determining a GIIC value based on the first and second measured fluorescence intensities, and for determining a performance of the analyte sensor based on the determined GIIC value; and

an output device for providing an output indicative of the determined performance.

11. The system of claim 10, wherein the analyte binding protein is a glucose binding protein.

12. The system of claim 10, wherein said analyte is glucose.

13. The system of claim 10, wherein a ratio between the first frequency component and the second frequency component for the dye is defined by:

R=(R0+Rinf([G]/KD))/(1+[G]/KD)

where

[G] is the analyte concentration;

R is the ratio at a given analyte concentration;

R0 is the ratio of spectral bands at zero analyte concentration;

Rinf is the ratio of spectral bands at infinite (saturating) analyte concentration; and

KD is an apparent dissociation constant for the system.

14. The system of claim 13, wherein the analyte is glucose, and [G] is the glucose concentration.

15. The system of claim 13, wherein a glucose independent intensity is calculated according to the following equation:

GII=(KDg/KDb−

1)*Fb*Fg+Fb*(Fginf−

(KDg/KDb)*Fg0)+Fg(Fb0−

(KDg/KDb)*Fbinf)

where

GII is the glucose independent intensity;

Fb is the measured intensity of the first frequency component;

Fg is the measured intensity of the second frequency component;

KDg is the apparent dissociation constant determined when using only the second frequency component;

KDb is the apparent dissociation constant determined when using only the first frequency component;

Fginf is the intensity of the second frequency component at saturated concentration;

Fg0 is the intensity of the second frequency component at zero concentration;

Fbinf is the intensity of the first frequency component at saturated concentration; and

Fb0 is the intensity of the first frequency component at zero concentration.

16. The system of claim 10, wherein the processor processes raw sensor signals and also calculates analyte concentration.

17. The system of claim 10, wherein the first frequency component and the second frequency component are selected to be far from the isosbestic frequency but closer than frequencies at which the signal to noise ratio drops below 10% of the maximum signal to noise ratio.

18. The system of claim 10, wherein the first fluorescent intensity is generated by a first dye and the second fluorescent intensity is generated by a second dye.