Apparatus and methods of raman spectroscopy for analysis of blood gases and analytes

• US 5,615,673 A
• Filed: 03/27/1995
• Issued: 04/01/1997
• Est. Priority Date: 03/27/1995
• Status: Expired due to Term

• Current Assignee: Massachusetts Institute of Technology
• Original Assignee: Massachusetts Institute of Technology
• Inventors: Wang, Yang, Brennan, James F. III, Berger, Andrew J., Tanaka, Kaz, Feld, Michael S., Itzkan, Irving, Dasari, Ramanchandra R.
• Primary Examiner(s): Sykes, Angela D.
• Assistant Examiner(s): WINAKUR, ERIC FRANK
• Application Number:
  US08/410,927
• Time in Patent Office: 736 Days
• Field of Search: 128/633, 128/664, 128/665, 356/39, 356/301
• US Class Current: 600/326
• CPC Class Codes: A61B 2562/12 Manufacturing methods specially adapted for producing sensors for in-vivo measurements
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• 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 5/14551 for measuring blood gases
• CPC Class Codes: G01J 3/02 Details
• CPC Class Codes: G01J 3/021 using plane or convex mirrors, parallel phase plates, or particular reflectors
• CPC Class Codes: G01J 3/0221 the fibers defining an entry slit
• CPC Class Codes: G01N 2021/656 Raman microprobe
• CPC Class Codes: G01N 21/65 Raman scattering

Abstract

The present invention relates to systems of methods of measuring selected analytes in blood and tissue using Raman spectroscopy to aid in diagnosis. More particularly, Raman spectra are collected and analyzed to measure the concentration of dissolved gases and other analytes of interest in blood. Methods include in vivo transdermal and continuous monitoring as well as in vitro blood analysis.

Claims

1. A method of measuring a dissolved gas in blood comprising the steps of:

irradiating blood with laser radiation having a wavelength such that Raman scattering occurs in a dissolved gas in the irradiated blood;

collecting Raman scattered light from the dissolved gas; and

detecting the collected Raman-scattered light from the dissolved gas in response to the laser radiation.

2. The method of claim 1 further comprising determining a concentration of the dissolved gas in the blood.

3. The method of claim 2 further comprising determining the concentration of a dissolved gas selected from the group comprising O₂, and CO₂.

4. The method of claim 1 wherein the laser wavelength is within the range of 700-1000 nm.

5. The method of claim 1 further comprising generating a spectral representation from the detected light and analyzing the spectral representation to measure a plurality of blood analytes.

6. The method of claim 1 further comprising providing an optical collimator on the distal end of a fiber optic device and collecting the Raman scattered light through the optical collimator.

7. The method of claim 1 further comprising providing a fiber optic probe coupled to a laser and irradiating said blood with radiation through the fiber optic probe.

8. The method of claim 1 further comprising providing a fiber optic collector for collecting the Raman scattered light.

9. The method of claim 8 further comprising providing a first optical filter between a laser source of the radiation and the irradiated blood and providing a second optical filter between the irradiated blood and the fiber optic collector.

10. A method of spectroscopic analysis of blood comprising the steps of:

transdermally irradiating blood through a portion of tissue with laser radiation having an excitation wavelength; and

detecting Raman-scattered light from the blood in response to the laser radiation, the Raman-scattered light having a wavelength different from the excitation wavelength of the laser radiation.

11. The method of claim 10 further comprising coupling the laser radiation to the tissue with a first fiber optic device and collecting the Raman-scattered light with a second fiber optic device, the second fiber optic device being coupled to a detector which detects the Raman-scattered light.

12. The method of claim 11 further comprising filtering the laser radiation with a first optical filtering device and filtering the Raman-scattered light with a second optical filtering device to remove any background light including Raman-scattered light produced by the first fiber optic device or the second fiber optic device.

13. The method of claim 10 further comprising analyzing the Raman-scattered light to extract concentration levels of blood gases and analytes in the blood.

14. The method of claim 10 further comprising irradiating the blood with radiation having a wavelength in a range of 700-1000 nm.

15. The method of claim 10 further comprising detecting dissolved blood gases and an electrolyte in the blood.

16. The method of claim 15 wherein the step of detecting blood gasses further comprises detecting a dissolved blood gas selected from the group comprising O₂ and CO₂.

17. The method of claim 10 further comprising providing an optical concentrator for collecting Raman scattered light from the blood, the collected light being optically coupled to a detector.

18. A method of spectroscopically monitoring blood comprising the steps of:

positioning a probe in proximity to a lumen containing the blood of a patient;

periodically irradiating a region of the blood within the lumen with laser radiation having an excitation wavelength; and

detecting Raman-scattered light from the blood in response to the periodic laser radiation, the Raman-scattered light having a wavelength different from the wavelength of the excitation laser radiation.

19. The method of claim 18 further comprising coupling the laser radiation to tissue overlying the blood with a first fiber optic device and collecting the Raman-scattered light with a second fiber optic device, the second fiber optic device being coupled to a detector which detects the Raman-scattered light.

20. The method of claim 18 further comprising filtering the laser radiation pulses with a first optical filtering device and filtering the Raman-scattered light with a second optical filtering device to remove any background light including Raman-scattered light produced by the first fiber optic device or the second fiber optic device.

21. The method of claim 18 further comprising analyzing the Raman-scattered light to extract concentration levels of blood gases and analytes in the blood region.

22. A method of spectroscopic analysis of blood comprising the steps of:

irradiating a dissolved gas in blood with laser radiation;

detecting a spectrum of Raman-scattered light returning from the dissolved gas in response to the laser radiation, the Raman-scattered light having a plurality of wavelengths different from the wavelength of the excitation laser radiation; and

subtracting a background spectrum from the detected spectrum.

23. The method of claim 22 further comprising coupling the laser radiation to the sample with a first fiber optic device and collecting the Raman-scattered light with a second fiber optic device, the second fiber optic device being coupled to a detector which detects the Raman-scattered light.

24. The method of claim 23 further comprising filtering the laser radiation with a first optical filtering device and filtering the Raman-scattered light with a second optical filtering device to remove any background light including Raman-scattered light produced by the first fiber optic device or the second fiber optic device.

25. The method of claim 22 further comprising analyzing the Raman-scattered light to determine concentration levels of blood gases and analytes in the sample.

26. The method of claim 22 further comprising providing a diode laser for irradiating the blood.

27. A transdermal spectroscopic diagnostic system for analyzing human blood comprising:

a laser emitting radiation in the infrared spectrum at

a wavelength to penetrate a layer of tissue;

a fiber optic device optically coupled to the laser for delivering the infrared radiation through the layer of tissue to irradiate a region of blood underlying the tissue;

a first optical filter having an input end coupled to a distal end of the fiber optic device that filters light, and an output end for passing the laser radiation;

an optical concentrator which comprises a cavity that reflects light and an aperture at a distal end that collects light, including the Raman-scattered light from blood over a range of incident angles, and an output path at the proximal end having a diameter larger than that of the aperture for transmitting collected light, coupled to the output end of the first filter;

a fiber optic bundle having an input end coupled to a second optical filter for passing the Raman-scattered light and an output end for delivering the Raman-scattered light, and

a detector coupled to the output end of the fiber optic bundle for detecting the Raman-scattered light; and

a data processor that determines a concentration level of an analyte in blood.

28. Amended The system of claim 27, wherein the detector comprises:

a first subsystem comprising a spectrograph coupled to a charge-coupled-device for detecting the Raman-scattered light, and

a second subsystem comprising an analyzer that determines a concentration level of a dissolved blood gas or analyte from the detected Raman-scattered light.

29. The system of claim 27, wherein the first filter comprises a holographic bandpass filter and further comprising a holographic dichroic beamsplitter.

30. The system of claim 27, wherein the optical concentrator comprises a compound parabolic concentrator.

31. The system of claim 27, wherein the fiber optic bundle comprises an aperture at the input end that is approximately equal in dimension to the diameter of the output path of the concentrator, and the output end having fiber optic strands configured in a plurality of vertical columns corresponding to the resolution of the detector.

32. A method of measuring a dissolved gas in blood comprising the steps of:

irradiating blood with laser radiation having a wavelength in the range of 700 to 1300 nm such that Raman scattering occurs in a dissolved gas in the irradiated blood;

collecting Raman scattered light from the dissolved gas; and

detecting the collected Raman-scattered light from the dissolved gas in response to the laser radiation.

33. The method of claim 32 further comprising determining a concentration of the dissolved gas in the blood.

34. The method of claim 33 further comprising determining the concentration of a dissolved gas selected from the group comprising O₂, and CO₂.

35. The method of claim 32 wherein the laser wavelength is within the range of 800-1000 nm.

36. The method of claim 32 further comprising generating a spectral representation from the detected light and analyzing the spectral representation to measure a plurality of blood analytes.

37. The method of claim 32 further comprising providing an optical collimator on the distal end of a fiber optic device and collecting the Raman scattered light through the optical collimator.

38. The method of claim 32 further comprising providing a fiber optic probe coupled to a laser and irradiating said blood with radiation through the fiber optic probe and collecting the Raman-scattered light.