Method of sample control and calibration adjustment for use with a noninvasive analyzer

• US 20050014997A1
• Filed: 05/18/2004
• Published: 01/20/2005
• Est. Priority Date: 08/14/1997
• Status: Active Grant

• Current Assignee: GLT Acquisition Corporation
• Original Assignee: Sensys Medical, Inc. (Sensys Medical Limited)
• Inventors: Ruchti, Timothy L., Hazen, Kevin H., Blank, Thomas B.
• Granted Patent: US 7,383,069 B2
• Time in Patent Office: Days
• US Class Current: 600/310
• 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: A61B 5/1495 Calibrating or testing of in-vivo probes
• CPC Class Codes: G01N 21/274 Calibration, base line adjustment, drift correction
• CPC Class Codes: G01N 21/359 using near infrared light

Abstract

A method and apparatus for easing the use of an optically based noninvasive analyzer is presented. More particularly, a simplified algorithm is used that removes the daily requirement of collecting and using a noninvasive spectrum to update a calibration model. In another embodiment, a guide is used to substantially reduce variation in sample probe placement in relation to a skin tissue sampling site, resulting in the ability to maintain calibration performance with the use of a reference analyte concentration, with or without the use of a reference spectrum collected nearby in time.

Claims

1. A noninvasive method for estimating a biological attribute of human tissue of a tested subject, comprising the steps of:

providing an apparatus for measuring light throughput, said apparatus comprising an energy source emitting light, an input element, an output element, and a spectrum analyzer;

coupling said input and output elements to a targeted and controlled sample volume of said human tissue;

irradiating said tissue through said input element with multiple wavelengths of said light energy, wherein said sample volume results in partial absorption of said light;

collecting at least a portion of non-absorbed light energy with said output element;

determining the intensities of said collected portion;

generating a model, wherein said model uses calibration noninvasive spectra and calibration reference concentrations;

adjusting said model with an estimated error, wherein said estimated error is generated with a spectrum of said targeted and controlled sample volume and with at least one direct reference measurement;

collecting at least one prediction noninvasive spectrum of said targeted and controlled tissue volume of said tested subject; and

estimating said biological attribute concentration of said tested subject using said adjusted model.

2. The method of claim 1, wherein said biological attribute comprises a glucose concentration.

3. The method of claim 1, wherein said light comprises near-infrared energy.

4. The method of claim 3, wherein said near-infrared region comprises 1100 to 1900 nm or at least one sub-range therein.

5. The method of claim 1, wherein said calibration noninvasive spectra comprise spectra from any of:

a single individual;

multiple individuals;

a single analyzer; and

multiple analyzers.

6. The method of claim 1, wherein said model comprises a multivariate analysis.

7. The method of claim 6, wherein said multivariate analysis comprises at least one of principal component regression and partial least squares.

8. The method of claim 1, wherein said direct reference measurement comprises at least one glucose concentration.

9. The method of claim 1, where said adjusting said model comprises:

y_meas=y_hat+y_err=X_measuredW^T+y_err,

wherein X_measured comprises a vector of a prediction spectrum, W^T comprises a vector of coefficients associated with the said regression model, y_hat comprises a resulting analyte concentration generated by said model prior to any correction, y_err provides an estimated error of said resulting analyte concentration, and y_meas comprises said biological attribute concentration.

10. The method of claim 1, wherein use of said adjusted model comprises a time period of at least one of:

a fraction of a day;

a work day;

a waking portion of a day;

a week; and

a month.

11. The method of claim 10, wherein said direct reference measurement comprises any of:

a single reference glucose concentration;

a reference glucose concentration determined before or in time proximity to beginning of said time period; and

a set of at least two glucose concentrations.

12. The method of claim 1, further comprising a guide with a sample side and an attachment side wherein said sample side of said guide replaceably attaches to said human tissue and said attachment side of said guide replaceably attaches to at least one of said input element and said output element.

13. The method of claim 11, wherein said sample side of said guide comprises at least one of:

a flat surface, and

a surface with a radius of curvature ranging from flat to 1.5 centimeters.

14. A noninvasive method for estimating a biological attribute concentration in human tissue of a tested subject, comprising the steps of:

generating a model, using noninvasive spectra and associated reference concentrations;

adjusting said model with at least one direct reference measurement and without use of a corresponding reference spectrum;

collecting at least one noninvasive spectrum of said tissue of said tested subject with an analyzer; and

estimating said biological attribute of said specific subject using said adjusted model.

15. The method of claim 14, further comprising a guide wherein said guide replaceably couples said analyzer to said human tissue.

16. A noninvasive method for estimating a biological attribute concentration of human tissue of a tested subject, comprising the steps of:

providing an apparatus for measuring light throughput, said apparatus comprising an energy source emitting light at multiple wavelengths, an input element, an output element, and a spectrum analyzer;

coupling said input and output elements to said human tissue using a guide, wherein said guide comprises an attachment side and a sample side;

irradiating said tissue through said input element with multiple wavelengths of said light with resulting absorption of at least some of said wavelengths;

collecting at least a portion of non-absorbed light with said output element;

determining the intensities of said collected light;

generating a model using calibration spectra and calibration reference concentrations;

adjusting said model with at least one direct reference measurement and a corresponding reference spectrum;

collecting at least one noninvasive prediction spectrum of said tissue of said tested subject; and

estimating said biological attribute of said specific subject using said adjusted model.

17. The method of claim 16, wherein said biological attribute comprises a glucose concentration.

18. The method of claim 16, wherein said light comprises wavelengths from 1100 to 1900 nm or at least one sub-range therein.

19. The method of claim 16, wherein said noninvasive calibration spectra comprise spectra from any of:

a single individual;

multiple individuals;

a single analyzer; and

multiple analyzers.

20. The method of claim 16, wherein said model comprises a multivariate analysis.

21. The method of claim 20, wherein said multivariate analysis comprises at least one of principal component regression and partial least squares.

22. The method of claim 16, wherein use of said adjusted model occurs for a time period comprising at least one of:

a fraction of a day;

a work day;

a waking portion of a day;

a week; and

a month.

23. The method of claim 22, wherein said direct reference measurement comprises any of:

a single reference glucose concentration;

a reference glucose concentration determined before or in time proximity to beginning of said time period;

the first n reference glucose concentrations of said time period; and

a set of at least two glucose concentrations.

24. The method of claim 22, wherein said reference spectrum comprises any of

a stored reference spectrum;

a first spectrum of said time period;

a spectrum of said specific subject;

an average of the first n spectra of said time period;

an average of the first n spectra of said specific subject;

a set of at least two spectra of said specific subject; and

a spectrum from a data base, wherein said spectrum is selected based upon at least one spectral feature.

25. The method of claim 16, wherein said sample side of said guide replaceably attaches to said human tissue and said attachment side of said guide replaceably attaches to at least one of said input element and said output element.

26. The method of claim 16, wherein said sample side of said guide comprises at least one of:

a flat surface, and

a surface with a radius of curvature ranging from flat to 1.5 centimeters.

27. The method of claim 16, wherein said attachment side of said guide interfaces with at least one of:

a plug;

a photostimulator;

a sample module;

said input element; and

said output element.

28. A noninvasive method for estimating a biological attribute concentration of a targeted human tissue of a tested subject, comprising the steps of:

generating a model, using noninvasive spectra and associated reference concentrations;

adjusting said model with an associated spectrum, wherein said associated spectrum is selected based upon spectral features representative of said targeted tissue from at least one of;

a spectral library;

a linear combination of spectra; and

at least one spectrum of said tested subject.

29. A noninvasive method for measuring a biological attribute of human tissue of a tested subject, comprising the steps of:

providing an apparatus for measuring light throughput, said apparatus comprising an energy source emitting infrared energy at multiple wavelengths, an input element, an output element, and a spectrum analyzer;

coupling said input and output elements to said human tissue;

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

collecting at least a portion of the non-absorbed infrared energy with said output element;

determining the intensities of said infrared energy;

generating a model using calibration noninvasive spectra and calibration reference concentrations;

adjusting said model with at least one direct reference measurement and without use of a corresponding reference spectrum;

collecting at least one prediction noninvasive spectrum of said tissue of said tested subject; and

estimating said biological attribute concentration of said specific subject using said adjusted model.