Subsurface thermal gradient spectrometry

• US 5,900,632 A
• Filed: 03/12/1997
• Issued: 05/04/1999
• Est. Priority Date: 03/12/1997
• Status: Expired due to Fees

• Current Assignee: OptiScan Biomedical Corporation
• Original Assignee: OptiScan Biomedical Corporation
• Inventors: Kramer, Charles E., Braig, James R., Sterling, Bernhard B., Shulenberger, Arthur M., Goldberger, Daniel S., King, Richard A., Trebino, Rick
• Primary Examiner(s): Westin, Edward P.
• Assistant Examiner(s): Hanig, Richard
• Application Number:
  US08/820,378
• Time in Patent Office: 783 Days
• Field of Search: 250/339.03, 250/339.04, 250/339.05, 250/339.07, 250/339.09, 250/339.11, 250/252.1 R, 250/252.1 A, 250/253, 250/341.1, 250/341.5 , 250/341.6, 250/341.8
• US Class Current: 250/339.03
• CPC Class Codes: A61B 5/01 Measuring temperature of body parts ; Diagnostic temperature sensing, e.g. for malignant or inflamed tissue clinical contact thermometers G01K13/20
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/14539 for measuring pH
• CPC Class Codes: A61B 5/14546 for measuring analytes not otherwise provided for, e.g. ions, cytochromes
• CPC Class Codes: A61B 5/1455 using optical sensors, e.g. spectral photometrical oximeters
• CPC Class Codes: A61B 5/1491 Heated applicators
• CPC Class Codes: G01N 21/35 using infrared light G01N21/39 takes precedence
• CPC Class Codes: G01N 21/71 thermally excited

Abstract

Spectrometric methodology for non-invasively obtaining optical spectra from heterogeneous material for the identification and quantification of constituent compounds. There is provided a transient or steady state subsurface thermal gradient spectroscopic methodology for obtaining in vivo optical spectra relating to the concentration of η analytes at depths to around 330 microns in human tissue, and for determining that concentration from the spectra. The methodology is employable on a wide variety of spectrometric devices, and enables: a real time determination of both surface and reference intensities; a fast, efficient calibration of the spectrometric device; and results in the provision of an analytical parameter which avoids the measurement of the optical path length to enable the extremely accurate calculation of a ratio of concentrations of η analytes in the system under analysis.

Claims

1. Method for spectroscopically analyzing a material utilizing a spectrometric instrument and a means for inducing a thermal gradient in said material, the method comprising the steps of:

calibrating said instrument;

inducing said thermal gradient in said material;

responsive to said inducing step, determining the surface emission from said material, utilizing said spectrometric instrument;

further responsive to said inducing step, determining the reference intensity from said material, utilizing said spectrometric instrument;

independent of optical pathlength, determining a parameter from said surface emission and said reference intensity correlating to a property of said material; and

transmitting said parameter, as an electrical signal, for further processing.

2. Method for spectroscopically analyzing a heterogeneous material composed of a plurality of constituents, at least a portion of said plurality of said constituents further defining a corresponding plurality of analytes, the method utilizing an infrared spectrometric instrument and a means for inducing a thermal gradient in said material, and comprising the steps of:

calibrating said infrared spectrometric instrument;

inducing said thermal gradient in said material, said thermal gradient having a depth of penetration, said depth of penetration defining an optical pathlength;

utilizing said spectrometric instrument, measuring an infrared emission from said material;

calculating a surface emission from said infrared emission;

calculating a reference intensity from said infrared emission;

independent of said optical pathlength, determining a parameter correlating to a property of at least one analyte utilizing said reference intensity and said surface emission; and

transmitting said parameter as a signal.

3. The method of claim 2 wherein said calibrating step further comprises the step of measuring infrared emissions from said material;

and

calculating at least one value for calibrating said infrared spectrometric instrument.

4. The method of claim 3 wherein said calculating step further comprises the step of calculating at least one of the instrument background emission intensity and the reflected emission.

5. The method of claim 3 wherein said measuring step further comprises the step of measuring infrared emissions at all wavelengths.

6. The method of claim 2 wherein said calibrating step is performed prior to said step of inducing said thermal gradient in said material.

7. The method of claim 2 wherein said calibrating step is performed subsequent to said step of inducing said thermal gradient in said material.

8. The method of claim 2 wherein said calibrating step is performed prior to and subsequent to said step of inducing said thermal gradient in said material.

9. The method of claim 2 further comprising the steps of:

measuring an infrared emission at a specified wavelength; and

calculating said surface emission for said material at all wavelengths from said specified wavelength.

10. The method of claim 9 wherein said step of calculating said surface emission further comprises the step of specifying said specified wavelength to be in the range of about 2-14 micrometers.

11. The method of claim 10 wherein said step of calculating said surface emission further comprises the step of specifying said specified wavelength to be in the range of about 4-12.5 micrometers.

12. The method of claim 11 wherein said step of calculating said surface emission further comprises the step of specifying said specified wavelength to be in the range of about 5.5-6.5 micrometers.

13. The method of claim 12 wherein said step of calculating said surface emission further comprises the step of specifying a value of about 6 micrometers for said specified wavelength.

14. The method of claim 2 further comprising the steps of:

measuring an infrared emission at a specified wavelength; and

calculating said reference intensity for said material at all wavelengths from said specified wavelength.

15. The method of claim 14 wherein said step of calculating said surface emission further comprises the step of specifying said specified wavelength to be in the range of about 2-14 micrometers.

16. The method of claim 15 wherein said step of calculating said surface emission further comprises the step of specifying said specified wavelength to be in the range of about 4-12.5 micrometers.

17. The method of claim 16 wherein said step of calculating said surface emission further comprises the step of specifying said specified wavelength to be in the range of about 6-10 micrometers.

18. The method of claim 17 wherein said step of calculating said surface emission further comprises the step of specifying a value of about 8 micrometers for said specified wavelength.

19. The method of claim 2 wherein said step of determining a parameter correlating to a property of at least one analyte further consists of determining a parameter relating to the concentration of said at least one analyte.

20. The method of claim 19 wherein said step of determining a parameter relating to the concentration of said at least one analyte further consists of determining the ratio of the concentrations of said first analyte and a second analyte.

21. The method of claim 19 wherein said step of determining a parameter relating to the concentration of said at least one analyte further consists of determining the ratio of the concentrations of a plurality of analytes.

22. The method of claim 2 further comprising the step of selecting said plurality of analytes from the group consisting of water, glucose and protein.

23. The method of claim 2 wherein said step of transmitting said parameter as a signal further comprises the step of selecting said signal from the group consisting of electrical signal, optical signal, mechanical signal, visual signal, and pressure signal.

24. Method for spectroscopically analyzing a heterogeneous material composed of a plurality of constituents, at least a portion of said plurality of said constituents further defining a corresponding plurality of analytes, the method utilizing an infrared spectrometric instrument and a means for inducing a thermal gradient in said material, and comprising the steps of:

with said spectrometric instrument, measuring infrared emissions from said material at all wavelengths prior to inducing said thermal gradient;

determining an instrument background emission intensity and a reflected emission utilizing said infrared emissions from said material at all wavelengths prior to inducing said thermal gradient;

calibrating said spectrometric instrument utilizing at least one of said instrument background emission intensity and said reflected emission;

inducing said thermal gradient in said material, said thermal gradient having a depth of penetration, said depth of penetration defining an optical pathlength;

measuring an infrared emission from said material at a first specified wavelength utilizing said spectrometric instrument;

calculating a surface emission at all wavelengths utilizing said infrared emission from said material at said first specified wavelength;

measuring an infrared emission from said material at a second specified wavelength utilizing said spectrometric instrument;

calculating a reference intensity from said infrared emission utilizing said infrared emission from said material at said second specified wavelength;

independent of said optical pathlength, determining, from said reference intensity and said surface emission a parameter correlating to the ratio of the concentrations of at least a first analyte to at least a second analyte; and

transmitting said parameter as an electrical signal.

25. The method of claim 24 further comprising the steps of:

measuring, with said spectrometric instrument, infrared emissions from said material at all wavelengths subsequent to inducing said thermal gradient;

determining an instrument background emission intensity and a reflected emission utilizing said infrared emissions from said material at all wavelengths subsequent to inducing said thermal gradient; and

calibrating said spectrometric instrument utilizing at least one of said instrument background emission intensity and said reflected emission.

26. Method for spectroscopically analyzing a material utilizing a spectrometric instrument and a means for inducing a thermal gradient in said material, the method comprising the steps of:

calibrating said instrument; and

subsequent to said step of calibrating said instrument, transmitting, as an electrical signal, a parameter related to said thermal gradient induced in said material, for further processing.

27. Method for spectroscopically analyzing a material utilizing a calibrated spectrometric instrument and a means for inducing a thermal gradient in said material, the method comprising the steps of:

responsive to inducing said thermal gradient, determining the surface emission from said material utilizing said calibrated spectrometric instrument; and

transmitting, as an electrical signal, a value derived from said surface emission for further processing.

28. Method for spectroscopically analyzing a material utilizing a calibrated spectrometric instrument and a means for inducing a thermal gradient in said material, the method comprising the steps of:

responsive to inducing said thermal gradient, determining the reference intensity from said material utilizing said calibrated spectrometric instrument; and

transmitting, as an electrical signal, a value derived from said reference intensity for further processing.

29. Method for spectroscopically analyzing a material utilizing a spectrometric instrument and a means for inducing a thermal gradient in said material, the method comprising the steps of:

independent of optical pathlength, determining a parameter from said thermal gradient correlating to a property of said material; and

transmitting said parameter, as an electrical signal, for further processing.

30. Method for spectroscopically analyzing a heterogeneous material composed of a plurality of constituents, at least a portion of said plurality of said constituents further defining a corresponding plurality of analytes, the method utilizing a calibrated infrared spectrometric instrument and a means for inducing a thermal gradient in said material and comprising the steps of:

inducing said thermal gradient in said material, said thermal gradient having a depth of penetration, said depth of penetration defining an optical pathlength;

utilizing said spectrometric instrument, detecting infrared emissions from said material at a well-chosen wavelength;

responsive to said step of detecting infrared emissions from said material at a well-chosen wavelength, calculating the reference intensity from said material at all wavelengths;

independent of said pathlength and utilizing said reference intensity, determining a parameter correlating to a property of a constituent of said material; and

transmitting said parameter as a signal.

31. Method for spectroscopically analyzing a heterogeneous material composed of a plurality of constituents, at least a portion of said plurality of said constituents further defining a corresponding plurality of analytes, the method utilizing a calibrated infrared spectrometric instrument and a means for inducing a thermal gradient in said material and comprising the steps of:

calibrating said infrared spectrometric instrument;

inducing said thermal gradient in said material, said thermal gradient having a depth of penetration, said depth of penetration defining an optical pathlength;

utilizing said spectrometric instrument, detecting infrared emissions from said material at a well-chosen wavelength;

responsive to said step of detecting infrared emissions from said material at a well-chosen wavelength, calculating the surface emission from said material at all wavelengths;

independent of said pathlength and utilizing said surface emission, determining a parameter correlating to a property of a constituent of said material; and

transmitting said parameter as a signal.

32. Method for spectroscopically analyzing a heterogeneous material composed of a plurality of constituents, at least a portion of said plurality of said constituents further defining a corresponding plurality of analytes, the method utilizing a infrared spectrometric instrument and a means for inducing a thermal gradient in said material and comprising the steps of:

utilizing said spectrometric instrument, detecting infrared emissions from said material at all wavelengths prior to inducing said thermal gradient;

inducing said thermal gradient in said material;

utilizing said spectrometric instrument, detecting infrared emissions from said material at all wavelengths subsequent to inducing said thermal gradient;

utilizing said infrared emissions from said material at all wavelengths prior to inducing said thermal gradient, and said infrared emissions from said material at all wavelengths subsequent to inducing said thermal gradient, calculating the instrument background emission intensity and reflected emission;

utilizing said instrument background emission intensity and reflected emission calibrating said instrument;

subsequent to said step of calibrating said instrument, determining with said instrument at least one parameter relating to at least one of said analytes; and

transmitting said parameter as a signal.

33. Method for spectroscopically analyzing a heterogeneous material composed of a plurality of constituents, at least a portion of said plurality of said constituents further defining a corresponding plurality of analytes, the method utilizing a calibrated infrared spectrometric instrument and a means for inducing a thermal gradient in said material, said thermal gradient having a depth of penetration, said depth of penetration defining an optical pathlength, whereby at least one infrared spectrometric measurement is taken resulting in the determination of a reference intensity and a surface emission, the method further for determining a parameter relating to the concentration of at least one of said plurality of analytes and comprising the steps of:

independent of said optical pathlength, determining, from said reference intensity and said surface emission, said parameter further for determining the ratio of the concentrations of at least a first analyte to at least a second analyte.