Algorithms for calibrating an analyte sensor

• US 8,972,196 B2
• Filed: 06/04/2010
• Issued: 03/03/2015
• Est. Priority Date: 02/06/2007
• Status: Active Grant

• Current Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Inventors: Peyser, Thomas A., Gamsey, Soya, Romey, Matthew A., Markle, David R.
• Primary Examiner(s): BORIN, MICHAEL L
• Application Number:
  US12/794,466
• Publication Number:
  US 20100312483A1
• Time in Patent Office: 1,733 Days
• US Class Current: 702/19
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/1455 using optical sensors, e.g. spectral photometrical oximeters
• CPC Class Codes: G01N 2021/6432 Quenching
• 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 21/6486 Measuring fluorescence of biological material, e.g. DNA, RNA, cells G01N21/6428 takes precedence
• CPC Class Codes: G01N 2201/062 LED's
• CPC Class Codes: G01N 2201/127 Calibration; base line adjustment; drift compensation
• CPC Class Codes: G01N 31/22 using chemical indicators G01N31/02 takes precedence
• 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 33/582 with fluorescent label
• CPC Class Codes: G01N 33/66 involving blood sugars, e.g. galactose

Abstract

Disclosed are embodiments that relate to algorithms and methods for calibrating an analyte sensor, and more particularly, to algorithms for calibrating an optical glucose sensor comprising an equilibrium fluorescent chemical indicator system. In particular, a method of detecting an analyte concentration is disclosed where a modified Michaelis-Menten equation comprising Michaelis-Menten parameters is used to characterize the signal generated by the analyte sensor.

Claims

1. A method for determining glucose concentration in a physiologic fluid, the method comprising:

providing an optical sensor comprising a non-enzymatic, equilibrium fluorescence chemical indicator system disposed along a distal region of an optical fiber, the chemical indicator system comprising a fluorophore operably coupled to a glucose binding moiety, wherein the fluorophore is configured to generate a fluorescent emission signal upon excitation with light, and wherein glucose binding to the glucose binding moiety causes a change in the fluorescent emission signal related to the glucose concentration in the physiologic fluid;

contacting the chemical indicator system with the physiologic fluid;

exciting the fluorophore with light, thereby generating a fluorescent emission signal related to the glucose concentration in the physiologic fluid;

detecting the intensity of the fluorescent emission signal;

obtaining a value of the fluorescent emission signal intensity in the absence of glucose;

obtaining a value of the asymptotic intensity of the fluorescent emission signal at infinite glucose;

obtaining a value of the glucose concentration at which the fluorescent emission intensity is one-half the difference between the fluorescent emission signal intensity in the absence of glucose and the asymptotic intensity of the fluorescent emission signal at infinite glucose; and

processing the fluorescent emission signal intensity by transforming the fluorescent emission signal intensity into a glucose concentration value using the equation;

[G]=c*(I−

a)/(a+b−

I), wherein

[G] is the glucose concentration,

I is the fluorescent emission signal intensity,

a is the value of the fluorescent emission signal intensity in the absence of glucose,

b is the value of the asymptotic signal intensity at infinite glucose concentration, minus the fluorescent signal intensity in the absence of glucose (a), and

c is the value of the glucose concentration at which the fluorescent signal intensity is one-half the difference between the asymptotic value (b) and the background (a).

2. The method of claim 1, wherein a, b and c are determined from a set of ex vivo measurements of the fluorescent emission signal(s) generated using one or more solutions of known glucose concentrations.

3. The method of claim 2, wherein a, b and c are determined during a factory calibration of the chemical indicator system.

4. The method of claim 3, further comprising an ex vivo calibration of the optical sensor using one or more solutions of known glucose concentration to determine a correction factor.

5. The method of claim 4, further comprising an in vivo or in vitro calibration with an independent glucose measurement.

6. The method of claim 4, wherein the ex vivo calibration comprises:

measuring a first fluorescent emission signal generated in the presence of a known glucose concentration at a first temperature and time; and

measuring a second fluorescent emission signal generated in the presence of the same known glucose concentration at a second temperature and time.

7. The method of claim 4, wherein the ex vivo calibration comprises:

measuring a first fluorescent emission signal generated in the presence of a known glucose concentration of 0 mg/dL, and

measuring a second fluorescent emission signal generated in the presence of a known glucose concentration of 100 mg/dL, and

measuring a third fluorescent emission signal generated in the presence of a known glucose concentration of 400 mg/dL.

8. The method of claim 1, further comprising:

measuring the fluorescent emission signal after contacting the chemical indicator system with the physiologic fluid,

measuring the glucose concentration in the physiologic fluid by a method independent of the chemical indicator system,

calculating a correction factor by comparing the measured fluorescent emission signal with a predicted signal calculated by the glucose concentration measured independently of the chemical indicator system; and

correcting a, b and c with the correction factor.

9. The method of claim 1, wherein the physiologic solution is blood.

10. The method of claim 1, wherein the optical sensor includes a mirror and a thermistor each placed at the distal end of the optical fiber, wherein the method further comprises sensing the temperature at the thermistor, and wherein the exciting the fluorophore with light includes reflecting the light off of the mirror into the optical fiber.