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

Assignee: Massachusetts Institute of Technology
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Filing: 1995-03-27
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Granted: 1997-04-01
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Expires: 2015-03-27
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Abstract

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.

Inventors

  • 👤 Andrew J. Berger
  • 👤 James F. Brennan, III
  • 👤 Ramanchandra R. Dasari
  • 👤 Michael S. Feld
  • 👤 Irving Itzkan
  • 👤 Kaz Tanaka
  • 👤 Yang Wang

Bibliographic Details

Application Number —
Jurisdiction US
Data Source google_patents
Last Synchronized 2026-10-25 20:01
CPC Classifications
G; G01; G01J; G01J3/00; G01J3/02; A; A61; A61B; A61B5/00; A61B5/145; A61B5/14532; A61B5/14546; A61B5/1455; A61B5/14551; G01J3/0205; G01J3/021; G01J3/0218; G01J3/0221; G01N; G01N21/00; G01N21/62; G01N21/63; G01N21/65; A61B2562/00; A61B2562/12; G01N2021/653; G01N2021/656

Claims Analysis

Total Claims: 44
Claim 1
Independent Claim 58 words
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.
Claim 2
Independent Claim 58 words
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.
Claim 3
Dependent Claim 17 words
The method of claim 1 further comprising determining a concentration of the dissolved gas in the blood.
Claim 4
Dependent Claim 26 words
The method of claim 2 further comprising determining the concentration of a dissolved gas selected from the group comprising O 2 , and CO 2 .
Claim 5
Dependent Claim 16 words
The method of claim 1 wherein the laser wavelength is within the range of 700-1000 nm.
Claim 6
Dependent Claim 27 words
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.
Claim 7
Dependent Claim 30 words
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.
Claim 8
Dependent Claim 27 words
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.
Claim 9
Dependent Claim 18 words
The method of claim 1 further comprising providing a fiber optic collector for collecting the Raman scattered light.
Claim 10
Dependent Claim 38 words
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.
Claim 11
Independent Claim 54 words
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.
Claim 12
Independent Claim 54 words
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.
Claim 13
Dependent Claim 46 words
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.
Claim 14
Dependent Claim 49 words
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.
Claim 15
Dependent Claim 23 words
The method of claim 10 further comprising analyzing the Raman-scattered light to extract concentration levels of blood gases and analytes in the blood.
Claim 16
Dependent Claim 21 words
The method of claim 10 further comprising irradiating the blood with radiation having a wavelength in a range of 700-1000 nm.
Claim 17
Dependent Claim 17 words
The method of claim 10 further comprising detecting dissolved blood gases and an electrolyte in the blood.
Claim 18
Dependent Claim 30 words
The method of claim 15 wherein the step of detecting blood gasses further comprises detecting a dissolved blood gas selected from the group comprising O 2 and CO 2 .
Claim 19
Dependent Claim 28 words
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.
Claim 20
Independent Claim 70 words
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.
Claim 21
Independent Claim 70 words
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.
Claim 22
Dependent Claim 48 words
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.
Claim 23
Dependent Claim 50 words
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.
Claim 24
Dependent Claim 24 words
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.
Claim 25
Independent Claim 63 words
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.
Claim 26
Independent Claim 63 words
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.
Claim 27
Dependent Claim 46 words
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.
Claim 28
Dependent Claim 49 words
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.
Claim 29
Dependent Claim 23 words
The method of claim 22 further comprising analyzing the Raman-scattered light to determine concentration levels of blood gases and analytes in the sample.
Claim 30
Dependent Claim 15 words
The method of claim 22 further comprising providing a diode laser for irradiating the blood.
Claim 31
Dependent Claim 207 words
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.
Claim 32
Dependent Claim 207 words
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.
Claim 33
Dependent Claim 49 words
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.
Claim 34
Dependent Claim 21 words
The system of claim 27, wherein the first filter comprises a holographic bandpass filter and further comprising a holographic dichroic beamsplitter.
Claim 35
Dependent Claim 14 words
The system of claim 27, wherein the optical concentrator comprises a compound parabolic concentrator.
Claim 36
Dependent Claim 55 words
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.
Claim 37
Independent Claim 66 words
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.
Claim 38
Independent Claim 66 words
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.
Claim 39
Dependent Claim 17 words
The method of claim 32 further comprising determining a concentration of the dissolved gas in the blood.
Claim 40
Dependent Claim 26 words
The method of claim 33 further comprising determining the concentration of a dissolved gas selected from the group comprising O 2 , and CO 2 .
Claim 41
Dependent Claim 16 words
The method of claim 32 wherein the laser wavelength is within the range of 800-1000 nm.
Claim 42
Dependent Claim 27 words
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.
Claim 43
Dependent Claim 30 words
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.
Claim 44
Dependent Claim 32 words
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.

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