Accommodating subject and instrument variations in spectroscopic determinations

• US 20040033618A1
• Filed: 08/16/2002
• Published: 02/19/2004
• Est. Priority Date: 10/13/1998
• Status: Active Grant

• Current Assignee: National Technology & Engineering Solutions Of Sandia LLC (Honeywell International Inc.)
• Original Assignee: Inlight Solutions, Inc.
• Inventors: Rowe, Robert K., Haass, Michael J., Thomas, Edward V.
• Granted Patent: US 7,098,037 B2
• Time in Patent Office: Days
• US Class Current: 436/171
• 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 21/359 using near infrared light
• CPC Class Codes: Y10T 436/10 Composition for standardization, calibration, simulation, stabilization, preparation or preservation; processes of use in preparation for chemical testing
• CPC Class Codes: Y10T 436/144444 Glucose

Abstract

A method and apparatus for measuring a biological attribute, such as the concentration of an analyte, particularly a blood analyte in tissue such as glucose. The method utilizes spectrographic techniques in conjunction with an improved instrument-tailored or subject-tailored calibration model. In a calibration phase, calibration model data is modified to reduce or eliminate instrument-specific attributes, resulting in a calibration data set modeling intra-instrument or intra-subject variation. In a prediction phase, the prediction process is tailored for each target instrument separately using a minimal number of spectral measurements from each instrument or subject.

Claims

1. A quantitative analysis instrument for measuring an unknown attribute level based on an indirect measurement of a biological sample, said instrument comprising:

a. a source of infrared energy generating multiple wavelengths;

b. an input sensor element for directing said wavelengths of infrared energy into said biological sample and an output sensor element for collecting at least a portion of the diffusely reflected infrared energy from said biological sample, said input and said output sensor elements adapted to optically couple to said biological sample;

c. at least one detector arranged for measuring the intensities of at least a portion of said wavelengths collected by said output sensor element; and

d. means for processing said master calibration information, said reference measurement information, and said indirect measurement information to generate a prediction of said unknown attribute level.

2. The instrument of claim 1, further comprising a memory device including master calibration information taken using one or more other instruments which has been developed in a manner that reduces instrument-specific attributes, reference measurement information from said instrument, and indirect measurement information from said instrument.

3. A quantitative analysis instrument for measuring an unknown attribute level based on an indirect measurement of a biological sample, said instrument comprising:

a. a source of infrared energy generating multiple wavelengths;

b. an input sensor element for directing said wavelengths of infrared energy into said biological sample and an output sensor element for collecting at least a portion of the diffusely reflected infrared energy from said biological sample, said input and said output sensor elements adapted to optically couple to said biological sample;

c. at least one detector arranged for measuring the intensities of at least a portion of said wavelengths collected by said output sensor element;

d. a memory device including master calibration information taken using one or more other instruments which has been developed in a manner that reduces instrument-specific attributes, reference measurement information from said instrument, and indirect measurement information from said instrument.

4. A method for generating a prediction result of a biological attribute on a slave instrument using spectroscopy as a surrogate indirect measurement for a direct measurement of said biological attribute, said method comprising the steps of:

a. using a modified calibration data set derived from calibration data taken from one or more master instruments processed in a manner that reduces the spectral variation due to instrument-specific attributes;

b. generating a calibration model through application of a multivariate algorithm that uses a composite calibration data set formed by combining the modified calibration data with one or more reference measurements; and

c. predicting said biological attribute in a target spectroscopic measurement utilizing said calibration model.

5. The method of claim 4, wherein the biological attribute comprises glucose concentration.

6. The method of claim 4, wherein the biological attribute comprises glycosolation effects.

7. A method for determining a biological attribute on a slave instrument by effectively using master calibration data, the method comprising:

a. using calibration data obtained from at least one master instrument, wherein said calibration data has been modified to reduce variations due to instrument-specific attributes generating calibration data with reduced instrument specific spectral attributes;

b. obtaining at least one indirect measurement with the slave instrument and a corresponding direct measurement;

c. developing a determination process that utilizes said master calibration data and said slave reference measurement; and

d. using said determination process to determine the unknown attribute in an indirect measurement made on said slave instrument.

8. The method of claim 7, wherein the biological attribute comprises glucose concentration.

9. The method of claim 7, wherein the biological attribute comprises glycosolation effects.

10. The method of claim 7, further comprising obtaining a direct measurement of the biological attribute.

11. A method for determining a variable, comprising:

a. obtaining a calibration data set of direct measurements and indirect spectral measurements of the variable from at least one master instrument, wherein the calibration data set has been modified to reduce variations therein due to instrument-specific attributes for each master instrument;

b. developing an instrument-specific calibration model from said modified calibration data set tailored for a specific instrument with at least one reference measurement of the variable from the specific instrument;

c. obtaining at least one indirect measurement of the variable for the specific instrument; and

d. using said instrument-specific calibration model and said at least one indirect measurement of the variable for the specific instrument to determine said variable in said specific instrument.

12. The method of claim 11, wherein the variable comprises an attribute of tissue.

13. The method of claim 11, wherein the variable comprises glucose concentration.

14. The method of claim 11, wherein the variable comprises glycosolation effects.

15. The method of claim 11, wherein the variable comprises an aspect of the state of the instrument.

16. The method of claim 11, wherein the variable comprises as aspect of the environment affecting the instrument.

17. A quantitative analysis instrument for measuring an unknown attribute level based on an indirect measurement of tissue, said instrument comprising:

a. a source of infrared energy generating multiple wavelengths;

b. an input sensor element for directing said wavelengths of infrared energy into said tissue and an output sensor element for collecting at least a portion of the diffusely reflected infrared energy from said tissue, said input and said output sensor elements adapted to optically couple to the surface of said tissue;

c. at least one detector arranged for measuring the intensities of at least a portion of said wavelengths collected by said output sensor element;

d. a memory device including master calibration information taken from one or more other instruments which has been developed in a manner that reduces instrument-specific attributes, reference measurement information from said instrument, and indirect measurement information from said instrument; and

e. means for processing said master calibration information, said reference measurement information, and said indirect measurement information to generate a prediction of said unknown attribute level.

18. A quantitative analysis instrument for measuring an unknown attribute level based on an indirect measurement of tissue, said instrument comprising:

a. a source of infrared energy generating multiple wavelengths;

b. an input sensor element for directing said wavelengths of infrared energy into said tissue and an output sensor element for collecting at least a portion of the diffusely reflected infrared energy from said tissue, said input and said output sensor elements adapted to optically couple to the surface of said tissue;

c. at least one detector arranged for measuring the intensities of at least a portion of said wavelengths collected by said output sensor element; and

d. means for processing said master calibration information, said reference measurement information, and said indirect measurement information to generate a prediction of said unknown attribute level.

19. A quantitative analysis instrument for measuring an unknown attribute level based on an indirect measurement of tissue, said instrument comprising:

a. a source of infrared energy generating multiple wavelengths;

b. an input sensor element for directing said wavelengths of infrared energy into said tissue and an output sensor element for collecting at least a portion of the diffusely reflected infrared energy from said tissue, said input and said output sensor elements adapted to optically couple to the surface of said tissue;

c. at least one detector arranged for measuring the intensities of at least a portion of said wavelengths collected by said output sensor element;

d. means for storing master calibration information taken from one or more other instruments which has been developed in a manner that reduces instrument-specific attributes, reference measurement information from said instrument, and indirect measurement information from said instrument.

20. A quantitative analysis instrument for non-invasive measurement of a biological attribute in human tissue, said instrument comprising:

a. a source of multiple wavelengths of infrared energy;

b. an input element for directing said wavelengths of infrared energy into said tissue and an output element for collecting at least a portion of the infrared energy exiting from said tissue, said input and said output elements adapted to optically couple to the surface of said tissue;

c. at least one detector for measuring the intensities of at least a portion of said wavelengths collected by said output element; and

d. means for processing said measured intensities and indicating a value for said biological attribute, said electronics including a processing method incorporated therein, said method utilizing calibration data taken from one or more other instruments which has been developed in a manner that reduces instrument-specific spectral attributes;

said method utilizing one or more reference measurements from said instrument.

21. The instrument of claim 20, wherein the output element collects infrared energy that is reflected from the tissue.

22. The instrument of claim 20, wherein the output element collects infrared energy that is transmitted through the tissue.

23. The instrument of claim 20, wherein the output element collects infrared energy that exits the tissue after reflection, transmission, or any combination thereof.

24. A method for generating a prediction result for use on a specific subject to predict a biological attribute of that subject using spectroscopy as a surrogate indirect measurement for a direct measurement of said biological attribute, said method comprising the steps of:

a. using a calibration data set that includes spectroscopic variation from a single subject;

b. generating a model by applying multivariate analysis to said calibration data set; and

c. using a prediction process to predict an unknown amount of said biological attribute in a target spectroscopic measurement that utilizes said model in conjunction with at least one matched measurement, wherein said matched measurement is obtained by using a spectral library and corresponding values of said biological attributes.

25. The method of claim 24, wherein the biological attribute comprises glucose concentration.

26. The method of claim 24, wherein the biological attribute comprises glycosolation effects.

27. A non-invasive method for measuring a biological attribute in human tissue of a specific subject comprising the steps of:

a. providing an apparatus for measuring infrared absorption, said apparatus including an energy source emitting infrared energy at multiple wavelengths, an input element, an output element and a spectrum analyzer;

b. providing an apparatus for making a direct measurement of the biological attribute;

c. coupling said input and output elements to said human tissue;

d. irradiating said tissue through said input element with multiple wavelengths of infrared energy with resulting absorption of at least some of said wavelengths;

e. collecting at least a portion of the non-absorbed infrared energy with said output element followed by determining the intensities of said infrared energy; and

f. predicting the biological attribute of said specific subject utilizing a model, wherein said model uses spectroscopic variation from multiple subjects and one or more reference measurements from said specific subject, each of said reference measurements including spectroscopic and corresponding direct measurement of said biological attribute.

28. The method of claim 27, wherein the biological attribute comprises glucose concentration.

29. The method of claim 27, wherein the biological attribute comprises glycosolation effects.

30. The method of claim 27, wherein the biological attribute comprises glucose concentration, and wherein the apparatus for making a direct measurement of the biological attribute comprises an invasive glucose concentration meter.