Method and apparatus for determining analyte concentration using phase and magnitude detection of a radiation transfer function

• US 6,944,486 B2
• Filed: 06/06/2003
• Issued: 09/13/2005
• Est. Priority Date: 03/12/1997
• Status: Expired due to Fees

• Current Assignee: OptiScan Biomedical Corporation
• Original Assignee: OptiScan Biomedical Corporation
• Inventors: Trembino, Rick, Kramer, Charles E., Braig, James R., Zheng, Peng, Sterling, Bernhard B., Shulenberger, Arthur M., Goldberger, Daniel S., King, Richard A., Barnes, Casper W.
• Primary Examiner(s): WINAKUR, ERIC FRANK
• Application Number:
  US10/456,109
• Publication Number:
  US 20040087841A1
• Time in Patent Office: 830 Days
• Field of Search: 600/309, 600/310, 600/316, 600/322, 600/473, 600/474, 250/341.6, 250/341.1, 250/341.5, 250/339.07, 250/339.09, 250/339.03, 250/339.04, 250/339.05, 250/339.12
• US Class Current: 600/310
• CPC Class Codes: A61B 5/0059 using light, e.g. diagnosis by transillumination, diascopy, fluorescence A61B5/0093, A61B5/1455, A61B5/02416 and A61B5/0261 take precedence
• CPC Class Codes: G01N 21/35 using infrared light G01N21/39 takes precedence

Abstract

A method and apparatus of determining the analyte concentration of a test sample is described. A temperature gradient is introduced into the test sample and infrared radiation detectors measure radiation at selected analyte absorbance peak and reference wavelengths. The modulation of the temperature gradient is controlled by a surface temperature modulation. A transfer function is determined that relates the surface temperature modulation to the modulation of the measured infrared radiation. Reference and analytical signals are detected. In the presence of the selected analyte, phase and magnitude differences in the transfer function are detected. These phase and magnitude differences, having a relationship to analyte concentration, are measured, correlated and processed to determine analyte concentration in the sample.

Claims

1. A method for detecting a concentration of a substance in a body, the method comprising:

inducing a time-varying temperature on a surface of the body, the temperature varying according to a surface temperature modulation;

detecting radiation emitted from the surface of the body, the emitted radiation having an emitted radiation modulation;

defining a first transfer function relating the emitted radiation modulation to (i) the surface temperature modulation and (ii) an absorbance; and

determining the absorbance based on the first transfer function.

2. The method of claim 1, further comprising determining a phase or a magnitude of the first transfer function based on the emitted radiation modulation and the surface temperature modulation.

3. The method of claim 1, further comprising determining the substance concentration based on the absorbance.

4. The method of claim 1, further comprising defining a second transfer function relating the surface temperature modulation with a depth-dependent temperature modulation within the body, wherein the body includes a plurality of layers and wherein the second transfer function comprises a piecewise solution to a thermal diffusion equation.

5. The method according to claim 1, wherein the surface temperature modulation is sinusoidal.

6. The method according to claim 1, wherein detecting comprises monitoring radiation at a plurality of discrete wavelengths.

7. An apparatus for detecting a concentration of a substance in a body, the apparatus comprising:

a thermal device adapted to induce a time-varying temperature on a body surface;

a detector adapted to detect radiation emitted from the body surface, the emitted radiation having an emitted radiation modulation;

a controller configured to drive the thermal device such that the time-varying temperature varies according to a surface temperature modulation; and

a signal processor connected to the detector and adapted to detect a phase and magnitude of the emitted radiation modulation, the signal processor including a transfer function that relates the surface temperature modulation to the emitted radiation modulation.

8. The apparatus according to claim 7, wherein the signal processor determines an expected emitted radiation modulation based on the transfer function and compares said expected emitted radiation modulation with the detected emitted radiation modulation.

9. The apparatus according to claim 7, wherein the transfer function comprises a function based on nominal values of constituent variables expected in the body.

10. The apparatus according to claim 7, wherein the transfer function comprises predetermined values corresponding to values measured in the body under known conditions.

11. The apparatus according to claim 7, wherein the thermal device is a heating device.

12. The apparatus according to claim 7, wherein the thermal device is a cooling device.

13. A method for determining an optical absorbance of a tissue comprising:

determining a thermal transfer function that relates a tissue surface temperature modulation to an internal tissue temperature modulation;

detecting radiation emitted from the tissue, the emitted radiation having an emitted radiation modulation;

defining a radiation transfer function that relates the emitted radiation modulation to the internal tissue temperature modulation, the radiation transfer function including the optical absorbance; and

determining a correlation between a phase or magnitude of the radiation transfer function and the optical absorbance.

14. The method of claim 13, further comprising determining a concentration of a substance in the tissue as a function of the determined optical absorbance.

15. An apparatus for detecting a concentration of a substance in a body, the apparatus comprising:

a thermal device adapted to induce a time-varying temperature on a body surface;

a detector adapted to detect radiation emitted from the body surface, the emitted radiation having an emitted radiation modulation;

a controller configured to drive the thermal device such that the time-varying temperature varies according to a surface temperature modulation; and

a signal processor connected to the detector and adapted to detect a phase and magnitude of the emitted radiation modulation, the signal processor including a plurality of model transfer functions that relate to a respective plurality of model responses between the surface temperature modulation and the emitted radiation modulation, wherein each model transfer function depends on a set of patient parameters.

16. The apparatus of claim 15, wherein the plurality of model transfer functions are stored in a memory.

17. The apparatus of claim 16, further comprising a communication device configured to connect the signal processor with the memory and to communicate a selected model transfer function to the signal processor, wherein the signal processor determines the concentration of the substance based on (i) the phase and magnitude of the emitted radiation modulation relative to the surface temperature modulation and (ii) the selected model transfer function.

18. The apparatus according to claim 17, wherein the communication device comprises a network adapted to communicate data between the memory at a first location and the signal processor at a second location.

19. The apparatus according to claim 18, wherein the network comprises the internet.

20. The apparatus according to claim 15, wherein the set of patient parameters comprise factors describing conditions of a human subject and wherein the body surface is a skin surface of a patient.

21. The apparatus according to claim 20, further comprising a computing device configured to select a model transfer function based on responses to questions regarding conditions of the patient.

22. A method for detecting a concentration of a substance in a body, the method comprising:

inducing a time-varying temperature on a surface of the body, the temperature varying according to a surface temperature modulation;

detecting radiation emitted from the surface of the body, the emitted radiation having an emitted radiation modulation; and

determining an absorbance based on a first transfer function which relates the emitted radiation modulation to (i) the surface temperature modulation and (ii) the absorbance.

23. The method of claim 22, further comprising determining a phase or a magnitude of the first transfer function based on the emitted radiation modulation and the surface temperature modulation.

24. The method of claim 22, further comprising determining the substance concentration based on the absorbance.

25. The method of claim 22, further comprising defining a second transfer function relating the surface temperature modulation with a depth-dependent temperature modulation within the body, wherein the body includes a plurality of layers and wherein the second transfer function comprises a piecewise solution to a thermal diffusion equation.

26. The method according to claim 22, wherein the surface temperature modulation is sinusoidal.

27. The method according to claim 22, wherein detecting comprises monitoring radiation at a plurality of discrete wavelengths.