System and method for diagnosing sensor performance using analyte-independent ratiometric signals

• US 10,466,247 B2
• Filed: 03/14/2013
• Issued: 11/05/2019
• Est. Priority Date: 11/20/2012
• Status: Active Grant

• Current Assignee: Becton, Dickinson & Co
• Original Assignee: Becton, Dickinson & Co
• Inventors: Keith, Steven
• Primary Examiner(s): Chin, Christopher L
• Application Number:
  US13/828,601
• Publication Number:
  US 20140141524A1
• Time in Patent Office: 2,427 Days
• Field of Search: None
• 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 system for performing a diagnostic test on an analyte sensor, comprising:

a sensing element comprising a polyethylene glycol matrix suspended analyte binding protein element introduced 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;

the sensing element disposed at a distal end of an optical conduit;

an excitation source at a proximal end of the optical conduit for supplying excitation energy to the optical conduit and a fluorescence intensity measuring device comprising first and second detectors 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 microprocessor that stores and executes program instructions to determine a GIIC value based on the first and second measured fluorescence intensities, and to determine a performance of the analyte sensor based on the determined GIIC value; and

an output device electrically connected to the microprocessor that receives the GIIC value from the microprocessor and provides an output indicative of the determined performance;

wherein said microprocessor executes program instructions to calculate a glucose independent intensity 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.

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

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

4. The system of claim 1, wherein said microprocessor calculates 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 system of claim 4, wherein the analyte is glucose, and [G] is the glucose concentration.

6. The system of claim 1, wherein the microprocessor processes raw sensor signals and also calculates analyte concentration.

7. The system of claim 1, wherein the first frequency and the second frequency are selected to be frequencies at which the signal to noise ratio is greater than 90% of the maximum signal to noise ratio.

8. The system 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.

9. A system for performing a diagnostic test on a glucose sensor, comprising:

a sensing element comprising a polyethylene glycol suspended glucose binding protein element suspended within a matrix for introduction to a glucose environment, said binding protein labeled with a dye fluorescing with an intensity spectrum related to a concentration of said analyte concentration in said environment;

the sensing element disposed at a distal end of an optical conduit;

an excitation source at a proximal end of the optical conduit for supplying excitation energy to the optical conduit and a fluorescence intensity measuring device comprising first and second detectors 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 microprocessor that stores and executes program instructions to determine a GIIC value based on the first and second measured fluorescence intensities, and for determining a performance of the glucose sensor based on the determined GIIC value; and

an output device device electrically connected to the microprocessor that receives the GIIC value from the processor and to provide an output indicative of the determined performance;

wherein said microprocessor executes program instructions to calculate a glucose independent intensity 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.