Method and device for detecting substances in body fluids by raman spectroscopy
First Claim
1. A method for the non-invasive determination of a concentration of a substance in a body fluid in a body tissue by Raman spectroscopy comprising the following steps:
- a) irradiating monochromatic primary light of a first wavelength into the body tissue, b) recording secondary light that is back scattered by the body tissue and storing the intensity of the secondary light in a first memory according to its wavelength as a first Raman spectral signal for the first primary wavelength, c) irradiating monochromatic primary light of a second wavelength into the body tissue, d) recording secondary light that is back scattered by the body tissue and storing the intensity of the secondary light in a second memory according to its wavelength as a second Raman spectral signal for the second primary wavelength, e) comparing the first Raman spectral signal in the first memory with the second Raman spectral signal in the second memory and generating a compare signal in which spectral structures caused by the body tissue are substantially eliminated, f) determining an intensity of the compare signal at at least one sample wavelength for which the intensity corresponds to the concentration of the substance in the body fluid.
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Abstract
The invention relates to a method and to a device for the non-invasive detection or determination, by Raman spectroscopy, of the concentration of substances in body fluids. The aim of the invention is to facilitate a non-invasive in vivo detection of substances in body fluids that allows for very accurate, reproducible results of analysis while requiring only little time for measuring which is acceptable for the patient. To this end, the inventive method and device for carrying out a Raman spectroscopy of a body fluid in a body tissue (1) records at least two Raman spectrums under different physical conditions and compares them with each other. The result of comparison allows detection of the substance one is looking for and measurement of the concentration of said substance.
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Citations
33 Claims
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1. A method for the non-invasive determination of a concentration of a substance in a body fluid in a body tissue by Raman spectroscopy comprising the following steps:
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a) irradiating monochromatic primary light of a first wavelength into the body tissue, b) recording secondary light that is back scattered by the body tissue and storing the intensity of the secondary light in a first memory according to its wavelength as a first Raman spectral signal for the first primary wavelength, c) irradiating monochromatic primary light of a second wavelength into the body tissue, d) recording secondary light that is back scattered by the body tissue and storing the intensity of the secondary light in a second memory according to its wavelength as a second Raman spectral signal for the second primary wavelength, e) comparing the first Raman spectral signal in the first memory with the second Raman spectral signal in the second memory and generating a compare signal in which spectral structures caused by the body tissue are substantially eliminated, f) determining an intensity of the compare signal at at least one sample wavelength for which the intensity corresponds to the concentration of the substance in the body fluid. - View Dependent Claims (4, 5, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17)
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2. A method for non-invasive determination of a concentration of a substance in a body tissue by Raman spectroscopy comprising the following steps:
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a) irradiating monochromatic primary light of a given wavelength into the body tissue at a first temperature of the body tissue, b) recording secondary light that is back scattered by the body tissue and storing the intensity of the secondary light in a first memory according to its wavelength as a first Raman spectral signal for the first temperature, c) irradiating monochromatic primary light of a given wavelength into the body tissue at a second temperature of the body tissue, d) recording secondary light that is back scattered from the body tissue and storing the intensity of the secondary light in a second memory according to its wavelength as a second Raman spectral signal for the second temperature, e) comparing the first Raman spectral signal in the first memory with the second Raman spectral signal in the second memory and generating a compare signal for which spectral structures caused by the body tissue are substantially eliminated, f) determining an intensity of the compare signal at at least one sample wavelength for which the intensity corresponds to the concentration of the substance in the body fluid. - View Dependent Claims (6, 7)
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3. A method for non-invasive determination of a concentration of a substance in a body tissue by Raman spectroscopy comprising the following steps:
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a) irradiating monochromatic primary light of a first wavelength into the body tissue at a first temperature of the body tissue, b) recording secondary light that is back scattered by the body tissue and storing the intensity of the secondary light in a first memory according to its wavelength as a first Raman spectral signal for the first wavelength and for the first temperature, c) irradiating monochromatic primary light of a second wavelength into the body tissue at a first temperature of the body tissue, d) recording secondary light that is back scattered by the body tissue and storing the intensity of the secondary light in a second memory according to its wavelength as a second Raman spectral signal for the second wavelength and for the first temperature, e) comparing the first Raman spectral signal in the first memory with the second Raman spectral signal in the second memory and generating a compare signal for which spectral structures caused by the body tissue are substantially eliminated, f) determining an intensity of the compare signal at at least one sample wavelength, g) repeating steps a) to f) for a second temperature and generating a second compare signal at at least one sample wavelength for which the intensity of the secondary light for the first and second wavelength are stored in a third and a fourth memory, respectively, and a second compare signal is generated, h) comparing the first and the second compare signal and, depending of the result of this comparison, generating an identification signal at at least one sample wavelength.
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18. A device for the non-invasive determination of a concentration of a substance in a body fluid in a body tissue by Raman spectroscopy comprising:
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a) a first light source for irradiating monochromatic primary light of a first wavelength into the body tissue, b) a photo detector means for recording secondary light that is backscattered from the body tissue, c) a first memory for storing the intensity of the secondary light according to its wavelength as a first Raman spectral signal for the first wavelength, d) a second light source for irradiating monochromatic primary light of a second wavelength into the body tissue, e) a second memory for storing the intensity of the secondary light according to its wavelength as a second Raman spectral signal for the second wavelength, f) a comparator means for comparing the first Raman spectral signal in the first memory with the second Raman spectral signal in the second memory and for generating a compare signal for which spectral structures caused by the body tissue are substantially eliminated, g) a discriminator unit for determining an intensity of the compare signal at at least one sample wavelength for which the intensity corresponds to the concentration of the substance in the body fluid. - View Dependent Claims (21, 22, 25, 26, 27, 28, 29, 30, 31)
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19. A device for the non-invasive determination of a concentration of a substance in a body fluid in a body tissue by Raman spectroscopy comprising:
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a) a light source for irradiating monochromatic primary light of a given wavelength into the body tissue, b) a heating means for adjusting a first temperature and a second temperature in the body tissue, c) a photo detector means for recording secondary light that is backscattered from the body tissue, d) a first memory for storing the intensity of the secondary light according to its wavelength as a first Raman spectral signal for the first temperature and a second memory for storing the intensity of the secondary light according to its wavelength as a second Raman spectral signal for the second temperature, e) a comparator means for comparing the first Raman spectral signal in the first memory with the second Raman spectral signal in the second memory and for generating a compare signal for which spectral structures caused by the body tissue are substantially eliminated, f) a discriminator unit for determining an intensity of the compare signal at at least one sample wavelength for which the intensity corresponds to the concentration of the substance in the body fluid. - View Dependent Claims (23, 24)
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20. A device for the non-invasive determination of a concentration of a substance in a body fluid in a body tissue by Raman spectroscopy comprising:
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a) a first light source for irradiating monochromatic primary light of a first wavelength into the body tissue, b) a second light source for irradiating monochromatic primary light of a second wavelength into the body tissue, c) a heating means for adjusting a first temperature and a second temperature in the body tissue, d) a photo detector means for recording secondary light that is backscattered from the body tissue, e) a first memory for storing the intensity of the secondary light according to its wavelength as a first Raman spectral signal for the first wavelength and for the first temperature, a second memory for storing the intensity of the secondary light according to its wavelength as a second Raman spectral signal for the second wavelength and for the first temperature, a third memory for storing the intensity of the secondary light according to its wavelength as a third Raman spectral signal for the first wavelength and for the second temperature and a fourth memory for storing the intensity of the secondary light according to its wavelength as a fourth Raman spectral signal for the second wavelength and for the second temperature, f) a first comparator means for comparing the first Raman spectral signal in the first memory with the second Raman spectral signal in the second memory and for generating a compare signal for which spectral structures caused by the body tissue are substantially eliminated, g) a second comparator means for comparing the third Raman spectral signal in the third memory with the fourth Raman spectral signal in the fourth memory and for generating a compare signal for which spectral structures caused by the body tissue are substantially eliminated, h) a third comparator means for comparing the first compare signal with the second compare signal for generating a third compare signal depending of the result of this comparison, i) a discriminator unit for determining an intensity of the third compare signal at at least one sample wavelength, j) an output unit for the output of an identification signal according to the intensity at at least one sample wavelength for which the intensity corresponds to the concentration of the substance in the body fluid.
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32. A method for the non-invasive determination of a concentration of a substance in a body fluid in a body tissue by Raman spectroscopy comprising the following steps:
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a) irradiating monochromatic primary light of a first wavelength into the body tissue at a first parameter value, b) recording secondary light that is back scattered by the body tissue and storing the intensity of the secondary light in a first memory according to its wavelength as a first Raman spectral signal for the first primary wavelength and for the first parameter value, c) repeating steps a) and b) for other primary wavelengths and other parameter values for which the intensity of the secondary light is stored in a further memory for each further primary wavelength and for each further parameter value, d) multivariate statistical comparison of the Raman signals for the determining at least one sample wavelength for which the intensity changes analogously to the parameter values, and e) determining and outputting the intensity at at least one sample wavelength in several Raman spectral signals according to the parameter values. - View Dependent Claims (33)
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Specification