ALGORITHMS FOR CALIBRATING AN ANALYTE SENSOR

• US 20150198607A1
• Filed: 01/23/2015
• Published: 07/16/2015
• Est. Priority Date: 02/06/2007
• Status: Abandoned Application

• 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.
• Application Number:
  US14/603,825
• Publication Number:
  US 20150198607A1
• Time in Patent Office: Days
• US Class Current: 1/1
• 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. -15. (canceled)

16. A measurement device for estimating glucose concentration comprising:

an optical sensor including a non-enzymatic, equilibrium fluorescence chemical indicator system disposed along a distal region of an optical fiber, the chemical indicator system including 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; and

a processing module configured to transform 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).

17. The measurement device of claim 16, wherein the optical sensor further includes:

at least one light source configured to generate light; and

at least one detector configured to detect the fluorescent emission signal intensity and generate a signal indicative of the glucose concentration.

18. The measurement device of claim 16, wherein the indicator system further includes an immobilizing matrix configured to prevent the fluorophore and/or the glucose binding moiety from diffusing out of the sensor.

19. The measurement device of claim 16, wherein the fluorophore is HPTS-triCys-MA.

20. The measurement device of claim 16, wherein the glucose binding moiety comprises boronic acid.

21. The measurement device of claim 16, wherein a, b and c are from a set of ex vivo measurements of the fluorescent emission signal(s) generated using one or more solutions of known glucose concentrations.

22. The measurement device of claim 16, wherein a, b and c are determined during a factory calibration of the chemical indicator system.

23. The measurement device of claim 16, further comprising a calibration system configured to perform an ex vivo calibration, the calibration system comprising:

one or more solutions with known glucose concentrations.

24. The measurement device of claim 16, the calibration system further comprising:

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

25. The measurement device of claim 16, wherein the processing module is configured to correct a, b and c by multiplying a, b, and c by a correction factor calculated by comparing an in vitro or in vivo measured signal with a predicted signal calculated by the analyte concentration measured independently of the measurement device.

26. The measurement device of claim 16, wherein the physiologic solution is blood.

27. The measurement device of claim 16, wherein the optical sensor includes a mirror and a thermistor each placed at the distal end of the optical fiber.

28. A measurement device for estimating glucose concentration comprising:

an optical sensor including a non-enzymatic, equilibrium fluorescence chemical indicator system disposed along a distal region of an optical fiber, the chemical indicator system including 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;

a detector operable to measure a fluorescent emission signal intensity generated by the fluorophore; and

a processing module configured to transform the fluorescent emission signal intensity into a glucose concentration value based on a value of the fluorescent emission signal intensity in the absence of glucose, a value of the asymptotic intensity of the fluorescent emission signal at infinite glucose, and 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, 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).

29. A measurement device for estimating glucose concentration comprising:

an optical sensor including a non-enzymatic, equilibrium fluorescence chemical indicator system disposed along a distal region of an optical fiber, the chemical indicator system including 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; and

a processing module configured to transform the fluorescent emission signal intensity into a glucose concentration value using the equation;

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

[X] is the glucose concentration,

F is the fluorescent emission signal intensity,

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

F_max is the maximum fluorescent emission 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.