Measurement devices and methods for measuring analyte concentration incorporating temperature and pH correction

• US 8,473,222 B2
• Filed: 03/11/2011
• Issued: 06/25/2013
• Est. Priority Date: 03/11/2010
• Status: Active Grant

• Current Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Original Assignee: GluMetrics, Inc.
• Inventors: Romey, Matthew A., Gamsey, Soya, Peyser, Thomas A.
• Primary Examiner(s): BORIN, MICHAEL L
• Application Number:
  US13/046,571
• Publication Number:
  US 20110224516A1
• Time in Patent Office: 837 Days
• Field of Search: None
• US Class Current: 702/23
• CPC Class Codes: A61B 2560/0247 for compensation or correction of the measured physiological value
• CPC Class Codes: A61B 2560/0252 using ambient temperature
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/1459 invasive, e.g. introduced into the body by a catheter A61B5/1464 takes precedence
• CPC Class Codes: A61B 5/1495 Calibrating or testing of in-vivo probes
• CPC Class Codes: G01N 2021/6419 Excitation at two or more wavelengths
• CPC Class Codes: G01N 2021/6484 Optical fibres
• CPC Class Codes: G01N 2021/7793 Sensor comprising plural indicators
• 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 21/7703 using reagent-clad optical fibres or optical waveguides using measurement of total internal reflection or attenuated total reflection G01N21/552; optical fibres or waveguides per se G02B
• CPC Class Codes: G06F 17/00 Digital computing or data processing equipment or methods, specially adapted for specific functions information retrieval, database structures or file system structures therefor G06F16/00

Abstract

Disclosed herein are methods of estimating an analyte concentration which include generating a signal indicative of the analyte concentration, generating a signal indicative of a temperature, generating a signal indicative of a pH, and transforming the signal indicative of the analyte concentration 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 data which includes temperature and pH calibration parameters, the signal indicative of a temperature, and the signal indicative of a pH. Also disclosed herein are measurement devices which employ the aforementioned methods.

Claims

1. A method of estimating glucose concentration in a physiologic fluid comprising:

contacting an optical sensor with the physiological fluid, wherein the optical sensor comprises 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 of the physiological fluid;

detecting the fluorescent emission signal indicative of the glucose concentration;

contacting a temperature sensing element with the physiological fluid, wherein the temperature sensing element is configured to generate a signal indicative of a temperature of the physiological fluid;

detecting the signal indicative of the physiological fluid temperature;

contacting a pH sensing element with the physiological fluid, wherein the pH sensing element is configured to generate a signal indicative of a pH of the physiological fluid;

detecting the signal indicative of the physiological fluid pH; and

transforming the fluorescent emission signal indicative of the glucose concentration utilizing the equation;

2. The method of claim 1, wherein the chemical indicator system, the temperature sensing element and the pH sensing element are incorporated within a single sensor.

3. The method of claim 1, wherein the fluorescent emission signal indicative of the glucose concentration, the signal indicative of the temperature, and the signal indicative of the pH are each generated from a set of at least three signals each of which is indicative of the temperature, the pH, and the glucose concentration.

4. The method of claim 1, wherein the temperature and pH calibration parameters are determined by a calibration method comprising:

selecting a first test glucose sensing element;

selecting three differing concentrations of glucose;

selecting a first temperature and a second temperature, the second differing from the first;

selecting a first pH and a second pH, the second differing from the first;

computing values of each of a_T,pH, b_T,pH, and c_T,pH at the first temperature by an_pH algorithm comprising fitting the equation to at least three signals indicative of the three differing concentrations of glucose in solution at the first temperature, the at least three signals generated using the first test glucose sensing element;

computing values of each of a_T,pH, b_T,pH, and c_T,pH at the second temperature by an algorithm comprising fitting the equation to at least three signals indicative of the three differing concentrations of glucose in solution at the second temperature, the at least three signals generated using the first test glucose sensing element;

computing values of each of a_T,pH, b_T,pH, and c_T,pH at the first pH by an algorithm comprising fitting the equation to at least three signals indicative of the three differing concentrations of glucose in solution at the first pH, the at least three signals generated using the first test glucose sensing element;

computing values of each of a_T,pH, b_T,pH, and c_T,pH at the second pH by an algorithm comprising fitting the equation to at least three signals indicative of the three differing concentrations of glucose in solution at the second pH, the at least three signals generated using the first test glucose sensing element;

selecting a first calibration equation relating a_T,pH to temperature and pH, the equation depending on a first set of the temperature and pH calibration parameters, and setting a value for each parameter based on the values of a_T,pH at the first temperature, the second temperature, the first pH, and the second pH;

selecting a second calibration equation relating b_T,pH to temperature and pH, the equation depending on a second set of the temperature and pH calibration parameters, and setting a value for each parameter based on the values of b_T,pH at the first temperature, the second temperature, the first pH, and the second pH; and

selecting a third calibration equation relating c_T,pH to temperature and pH, the equation depending on a third set of the temperature and pH calibration parameters, and setting a value for each parameter based on the values of c_T,pH at the first temperature, the second temperature, the first pH, and the second pH.

5. The method of claim 4, wherein:

the first calibration equation is the product of a first pH-independent function and a first temperature-independent function;

the second calibration equation is the product of a second pH-independent function and a second temperature-independent function; and

the third calibration equation is the product of a third pH-independent function and a third temperature-independent function;

wherein the first, second, and third temperature-independent functions are

τ

_aT(T)=m_aT*T+β

_aT,

τ

_bT(T)=m_bT*T+β

_bT, and

τ

_cT(T)=m_cT*T+β

_cT,

and wherein the first, second, and third temperature-independent functions are

ρ

_apH(pH)=m_apH*pH+β

a_pH,

ρ

_bpH(pH)=m_bpH*pH+β

b_pH, and

6. The method of claim 5, wherein:

the first, second, and third pH-independent functions are linear in temperature;

the first, and second temperature-independent functions are linear in pH; and

the third temperature-independent function is a fraction wherein the numerator is equal to an exponential function of a function linear in the inverse of pH, and the denominator is equal to an exponential function of the same function linear in the inverse of pH evaluated at fixed pH.

7. The method of claim 6, wherein transforming the signal indicative of the glucose concentration utilizing the equation comprises at least one of a_T,pH, b_T,pH, and c_T,pH substituted with a calibration equation functionally that depends on a set of one or more temperature calibration parameters, pH calibration parameters, the signal indicative of the temperature, and the signal indicative of the pH.

8. The method of claim 7, wherein the step of transforming the signal indicative of the glucose concentration utilizes the equation wherein:

a_T,pH has been substituted with a first calibration equation functionally depending on a first set of temperature and pH calibration parameters, the signal indicative of the temperature, and the signal indicative of the pH;

b_T,pH has been substituted with a second calibration equation functionally depending on a second set of temperature and pH calibration parameters, the signal indicative of temperature, and the signal indicative of pH; and

c_T,pH has been substituted with a third calibration equation functionally depending on a third set of temperature and pH calibration parameters, the signal indicative of temperature, and the signal indicative of pH.

9. The method of claim 1, wherein a_T,pH is defined by the equation a_T,pH=a₀*τ

_aT(T)*ρ

_apH(pH), wherein b_T,pH is defined by the equation b_T,pH=b₀*τ

_bT(T)*ρ

_bpH(pH), and wherein c_T,pH is defined by the equation c_T,pH=b₀*τ

_cT(T)*ρ

_cpH(pH).

10. The method of claim 1, wherein the temperature and pH calibration data are generated by a calibration method comprising:

providing at least three solutions of differing known glucose concentrations;

providing a first test glucose sensing element;

generating a first set of at least three signals using the first test glucose sensing element, each signal indicative of the concentration of glucose in a different solution of the at least three solutions at a first temperature and pH;

generating a second set of at least three signals using the first test glucose sensing element, each signal indicative of the concentration of analyte in a different solution of the at least three solutions at a second temperature and pH.

11. The method of claim 10, wherein the calibration method further comprises:

determining values of each of a_T,pH, b_T,pH, and c_T,pH at the first temperature and pH by an algorithm comprising fitting the equation to a first fit dataset comprising the first set of at least three signals;

determining values of each of and a_T,pH, b_T,pH, and c_T,pH at the second temperature and pH by an algorithm comprising fitting the equation to a second fit dataset comprising the second set of at least three signals;

selecting an equation relating a_T,pH, b_T,pH, and c_T,pH to temperature and pH, the_pH, equation depending on a first set, second set, and third set of temperature and pH calibration parameters respectively;

determining a value for each calibration parameter of the first, second, and third set of calibration parameters based on the value of a_T,pH, b_T,pH, and c_T,pH respectively at the first temperature and pH; and

determining a value for each calibration parameter of the first, second, and third set of calibration parameters based on the value of a_T,pH, b_T,pH, and c_T,pH respectively at the second temperature and pH.

12. The method of claim 11, wherein:

for the step of selecting an equation, equations linear in temperature and pH are selected to relate a_T,pH, b_T,pH, and c_T,pH to temperature and pH; and

wherein each of the first, second, and third sets of temperature and pH calibration parameters comprise a slope and an intercept relating temperature and pH to the value of either a_T,pH, b_T,pH, and c_T,pH.

13. The method of claim 11, wherein the calibration method further comprises:

providing a second test glucose sensing element;

generating a third set of at least three signals using the second test glucose sensing element, each signal indicative of the concentration of glucose in a different solution of the at least three solutions at the first temperature and pH;

generating a fourth set of at least three signals using the test glucose sensing element, each signal indicative of the concentration of glucose in a different solution of the at least three solutions at the second temperature and pH.

14. The method of claim 13, wherein generating values a_T,pH, b_T,pH, and c_T,pH at the first temperature and pH by an algorithm further comprises:

fitting the equation to a third fit dataset comprising the third set of at least three signals;

averaging the results of fitting the third fit dataset with the results of fitting the first fit dataset; and

determining each of a_T,pH, b_T,pH, and c_T,pH at the second temperature and pH by;

fitting a the equation to a fourth fit dataset comprising the fourth set of at least three signals; and

averaging the results of fitting the fourth fit dataset with the results of fitting the second fit dataset.