ALGORITHMS FOR CALIBRATING AN ANALYTE SENSOR

• US 20100312483A1
• Filed: 06/04/2010
• Published: 12/09/2010
• Est. Priority Date: 02/06/2007
• Status: Active Grant

• Current Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Original Assignee: GluMetrics, Inc.
• Inventors: MARKLE, DAVID R., ROMEY, MATTHEW A., PEYSER, THOMAS A., GAMSEY, SOYA
• Granted Patent: US 8,972,196 B2
• Time in Patent Office: 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 an analyte concentration in a solution or suspension, comprising:

providing a sensor comprising a chemical indicator system adapted to generate a signal related to the analyte concentration in the solution or suspension;

contacting the chemical indicator system with the solution or suspension, thereby generating the signal; and

determining the analyte concentration from the signal using a modified Michaelis-Menten equation comprising Michaelis-Menten parameters.

2. The method of claim 1, wherein the Michaelis-Menten parameters are determined from a set of ex vivo measurements of the signal using one or more solutions of known analyte concentrations.

3. The method of claim 2, wherein the Michaelis-Menten parameters are determined during a factory calibration of the chemical indicator system.

4. The method of claim 3, further comprising an ex vivo calibration with one or more solutions of known analyte concentration to determine a correction factor.

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

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

measuring the signal with 100 mg/dL of analyte at 42°

C. for 90 minutes; and

measuring the signal with 100 mg/dL of analyte at 33°

C. for 120 minutes.

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

measuring the signal with 0 mg/dL of analyte;

measuring the signal with 100 mg/dL of analyte; and

measuring the signal with 400 mg/dL of analyte.

8. The method of claim 1, further comprising:

measuring the signal after placement of the chemical indicator system in an in vitro or in vivo environment;

measuring the analyte concentration independent of the chemical indicator system;

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

correcting the Michaelis-Menten parameters with the correction factor.

9. The method of claim 1, wherein the modified Michaelis-Menten equation is:

[X]=c*(I−

a)/(a+b−

1), wherein

[X] is the analyte concentration

I is the signal intensity

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

c is the analyte concentration at which the signal intensity is one-half the difference between (b) and (a).

10. The method of claim 1, wherein the analyte is glucose, the chemical indicator system comprises a equilibrium fluorescence chemical indicator, the signal is a fluorescent signal and the modified Michaelis-Menten equation is:

F−

F_min+F_maxK[X]/(1+K[X]), wherein

[X] is the glucose concentration,

F is the fluorescent signal intensity,

F_min is the fluorescent signal intensity in the absence of glucose,

F_max is the maximum fluorescent signal intensity when the system is saturated with glucose, and

K is the binding affinity of the equilibrium fluorescence chemical indicator for glucose.

11. A measurement device for estimating an analyte concentration of a sample, the measurement device comprising:

an analyte sensing element comprising a chemical indicator system configured to generate a signal indicative of the analyte concentration; and

a processing module configured to transform the signal utilizing an equation of the form of a modified Michaelis-Menten equation depending on Michaelis-Menten parameters, wherein values of the Michaelis-Menten parameters are set based upon calibration data.

12. The measurement device of claim 11, further comprising a calibration system configured to perform an ex vivo calibration, the calibration system comprising:

one or more solutions with known analyte concentrations; and

a temperature controlling module configured to control the temperature of the one or more solutions with known analyte concentrations.

13. The measurement device of claim 11, wherein the processing module is configured to correct the Michaelis-Menten parameters by multiplying said parameters by a correction factor calculated by comparing the in vitro or in vivo measured signal with a predicted signal calculated by the analyte concentration measured independently of the measurement device.

14. The measurement device of claim 11, wherein the modified Michaelis-Menten equation is characterized by the equation:

[X]=c*(I−

a)/(a+b−

1), wherein

[X] is the analyte concentration

I is the signal intensity

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

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

15. The measurement device of claim 11, wherein the analyte is glucose, the chemical indicator system comprises a fluorophore operably coupled to a glucose binding moiety, the signal is a fluorescent signal, and the modified Michaelis-Menten equation is:

F=F_min+F_maxK[X]/(1+K[X]), wherein

[X] is the glucose concentration,

F is the fluorescent signal intensity,

F_min is the fluorescent signal intensity in the absence of glucose,

F_max is the maximum fluorescent signal intensity when the system is saturated with glucose, and

K is the binding affinity of the glucose binding moiety of the chemical indicator system.