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

• US 20040087841A1
• Filed: 06/06/2003
• Published: 05/06/2004
• Est. Priority Date: 03/12/1997
• Status: Active Grant

• Current Assignee: OptiScan Biomedical Corporation
• Original Assignee: Hercules Technology Growth Capital, Inc.
• Inventors: Kramer, Charles E., Braig, James R., Zheng, Peng, Sterling, Bernhard B., Shulenberger, Arthur M., Goldberger, Daniel S., King, Richard A., Trebino, Rick, Barnes, Casper W.
• Granted Patent: US 6,944,486 B2
• Time in Patent Office: Days
• 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 of analyzing a test sample utilizing a radiation detector, a data processing means, and a means for inducing a thermal gradient in said sample, said method comprising the steps of:

providing a test sample;

inducing a thermal gradient in said test sample;

responsive to said inducing step, measuring at least one reference signal emitted by said sample;

further responsive to said inducing step, measuring at least one analytical signal emitted by said sample;

comparing said reference and analytical signals to determine parameter information; and

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

2. 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;

defining a first transfer function relating a modulation emitted from the surface of the body to the surface temperature modulation, the first transfer function having a magnitude and phase that depend on an absorbance;

detecting the radiation emitted from the surface;

determining a phase or magnitude of the first transfer function based the modulation of the radiation emitted from the surface and the surface temperature modulation;

determining the absorbance based on the determined phase or magnitude; and

determining the substance concentration based on the absorbance.

3. The method according to claim 2, further comprising providing 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.

4. The method according to claim 2, further comprises providing where the surface temperature modulation as a sinusoid.

5. The method according to claim 2, wherein the step of detecting comprises monitoring radiation at a plurality of discrete wavelengths.

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

a thermal device adapted to induce a temperature differential at a surface of the body;

a detector adapted to monitor radiation, including radiation emitted from the body surface;

a controller coupled to drive the thermal device to vary the temperature at the surface according to a surface temperature modulation; and

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

7. The apparatus according to claim 6, wherein the signal processor operates to determine an expected modulation of emitted radiation based on the transfer function and compare said expected modulation with the detected modulation.

8. The apparatus according to claim 6, wherein the transfer comprises a function based on nominal values of constituent variables expected in the body.

9. The apparatus according to claim 6, wherein the transfer function comprises predetermined values corresponding to values measured in the body under known conditions.

10. The apparatus according to claim 6, wherein the thermal device is a heating device.

11. The apparatus according to claim 6, wherein the thermal device is a cooling device.

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

determining a thermal transfer function that relates a temperature modulation at a surface of a body to a depth-dependant temperature modulation within the body;

defining a radiation transfer function that relates a modulation of radiation emitted from the surface of the body to the depth-dependant temperature modulation, the radiation transfer function including the absorbance; and

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

13. The method of claim 12, further comprising determining a concentration of a substance in the body as a function of the determined optical absorbance.

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

a thermal device adapted to induce a temperature differential at a surface of the body;

a detector adapted to monitor radiation, including radiation emitted from the body surface;

a controller coupled to drive the thermal device to vary the temperature at the surface according to a surface temperature modulation;

a signal processor connected with the detector and adapted to detect a phase and magnitude of a modulation of the emitted radiation;

a memory, including a plurality of model transfer functions stored therein, the model transfer functions relating to a respective plurality of model responses between the surface temperature modulation and the modulation of the emitted radiation, wherein each model transfer function depends on a set of patient parameters; and

a communication device adapted to connect the signal processor with the memory and to communicate a selected one of the model transfer functions to the signal processor, wherein the signal processor determines the concentration of the substance based on the phase and magnitude of the emitted radiation relative to the temperature modulation and the selected model transfer function.

15. The apparatus according to claim 14, wherein the patient parameters comprise factors describing conditions of a human subject and wherein the surface of the body is a surface of the skin of the human subject.

16. The apparatus according to claim 15, further comprising a computing device connected to the memory for selecting the selected model transfer function based on responses to questions regarding conditions of the human subject.

17. The apparatus accordingly to claim 14, 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.

18. The apparatus according to claim 17, wherein the network comprises the Internet.