Method and devices for laser induced fluorescence attenuation spectroscopy
First Claim
1. A spectroscopic method of analyzing a sample, comprising:
- irradiating a sample with radiation to produce fluorescence from the sample, wherein the fluorescence is modulated by the sample;
monitoring a first portion of the modulated fluorescence at a first distance from the sample;
monitoring a second portion of the modulated fluorescence at a second distance from the sample, the second distance being different from the first distance;
and comparing the first and second portions of the modulated fluorescence to each other to determine a modulation characteristic of the sample.
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Accused Products
Abstract
The Laser Induced Fluorescence Attenuation Spectroscopy (LIFAS) method and apparatus preferably include a source adapted to emit radiation that is directed at a sample volume in a sample to produce return light from the sample, such return light including modulated return light resulting from modulation by the sample, a first sensor, displaced by a first distance from the sample volume for monitoring the return light and generating a first signal indicative of the intensity of return light, a second sensor, displaced by a second distance from the sample volume, for monitoring the return light and generating a second signal indicative of the intensity of return light, and a processor associated with the first sensor and the second sensor and adapted to process the first and second signals so as to determine the modulation of the sample. The methods and devices of the inventions are particularly well-suited for determining the wavelength-dependent attenuation of a sample and using the attenuation to restore the intrinsic laser induced fluorescence of the sample. In turn, the attenuation and intrinsic laser induced fluorescence can be used to determined a characteristic of interest, such as the ischemic or hypoxic condition of biological tissue.
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Citations
54 Claims
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1. A spectroscopic method of analyzing a sample, comprising:
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irradiating a sample with radiation to produce fluorescence from the sample, wherein the fluorescence is modulated by the sample;
monitoring a first portion of the modulated fluorescence at a first distance from the sample;
monitoring a second portion of the modulated fluorescence at a second distance from the sample, the second distance being different from the first distance;
andcomparing the first and second portions of the modulated fluorescence to each other to determine a modulation characteristic of the sample. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29)
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30. A spectroscopic method of analyzing a sample, comprising:
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irradiating a sample with radiation to produce return radiation from the sample, wherein the return radiation is modulated by the sample;
monitoring a first portion of the modulated return radiation at a first distance from the sample;
monitoring a second portion of the modulated return radiation at a second distance from the sample;
processing the first and second portions of the modulated return radiation to determine a modulation characteristic of the sample, wherein the return radiation is modulated by attenuation. - View Dependent Claims (31, 32, 33, 34, 35, 36)
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37. A spectroscopic method of analyzing a sample, comprising:
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irradiating a sample with radiation to produce return radiation from the sample, wherein the return radiation is modulated by the sample;
monitoring a first portion of the modulated return radiation at a first distance from the sample;
monitoring a second portion of the modulated return radiation at a second distance from the sample;
processing the first and second portions of the modulated return radiation to determine a modulation characteristic of the sample;
wherein the sample is biological material;
wherein the method further includes determining a physiological property of the tissue using the modulation characteristic; and
wherein the physiological property of the tissue is hypoxia.
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38. A spectroscopic method for determining the oxygenation of a biological material, comprising:
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irradiating a sample of a biological material with radiation to produce fluorescence from the sample, wherein the fluorescence is modulated by attenuation of the sample;
monitoring a first portion of the modulated fluorescence at a first distance from the sample;
monitoring a second portion of the modulated fluorescence at a second distance from the sample, the second distance being different from the first distance;
comparing the first and second portions of the modulated fluorescence to each other to determine the attenuation of the sample;
anddetermining oxygenation of the sample using the attenuation of the sample.
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39. A spectroscopic method for determining the oxygenation of a biological material, comprising:
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irradiating a sample of a biological material with radiation to produce return radiation from the sample, wherein the return radiation is modulated by attenuation of the sample;
monitoring a first portion of the modulated return radiation at a first distance from the sample;
monitoring a second portion of the modulated return radiation at a second distance from the sample;
processing the first and second portions of the modulated return radiation to determine the attenuation of the sample;
determining oxygenation of the sample using the attenuation of the sample;
wherein the oxygenation of the sample is determined by comparing the attenuation of the sample to the attenuation of a sample having a known level of oxygenation.
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40. A spectroscopic method for determining the concentration of hemoglobin in a biological material, comprising:
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irradiating a sample of biological material with radiation to produce fluorescence from the sample, wherein the fluorescence is modulated by attenuation of the sample;
monitoring a first portion of the modulated fluorescence at a first distance from the sample;
monitoring a second portion of the modulated fluorescence at a second distance from the sample, the second distance being different from the first distance;
comparing the first and second portions of the modulated fluorescence to each other to determine the attenuation of the sample;
anddetermining the concentration of hemoglobin in the sample using the attenuation of the sample.
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41. A spectroscopic method for determining the concentration of hemoglobin in a biological material, comprising:
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irradiating a sample of a biological material with radiation to produce return radiation from the sample, wherein the return radiation is modulated by attenuation of the sample;
monitoring a first portion of the modulated return radiation at a first distance from the sample;
monitoring a second portion of the modulated return radiation at a second distance from the sample;
determining the concentration hemoglobin in the sample using the attenuation of the sample;
wherein the concentration of hemoglobin is determined by comparing the attenuation of the sample to the attenuation of a sample having a known concentration of hemoglobin.
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42. A method for determining a physiological characteristic of a biological material, comprising:
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irradiating a sample of biological material with radiation to produce fluorescence from the sample, wherein the fluorescence is modulated by the sample;
monitoring a first portion of the modulated fluorescence at a first distance from the sample;
monitoring a second portion of the modulated fluorescence at a second distance from the sample, the second distance being different from the first distance;
andcomparing the first and second portions of the modulated fluorescence to each other, using a predictive model, to determine a physiological characteristic of the sample.
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43. A method for determining a physiological characteristic of a biological material, comprising:
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irradiating a sample of a biological material with radiation to produce return radiation from the sample, wherein the return radiation is modulated by the sample;
monitoring a first portion of the modulated return radiation at a first distance from the sample;
monitoring a second portion of the modulated return radiation at a second distance from the sample;
processing the first and second portions of the modulated return radiation, using a predictive model, to determine a physiological characteristic of the sample;
wherein the predictive model is a multivariate linear regression.
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44. A method for determining a physiological characteristic of biological material, comprising:
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irradiating a sample of biological material with radiation to produce fluorescence from the sample, wherein the fluorescence is modulated by the sample;
monitoring a first portion of the modulated fluorescence at a first distance from the sample;
monitoring a second portion of the modulated fluorescence at a second distance from the sample, the second distance being different from the first distance;
comparing the first and second portions of the modulated fluorescence to each other to determine a modulation characteristic of the sample;
andprocessing the modulation characteristic, using a predictive model, to determine a physiological characteristic of the sample.
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45. A method for determining a physiological characteristic of a biological material, comprising:
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irradiating a sample of a biological material with radiation to produce return radiation for the sample, wherein the return radiation is modulated by the sample;
monitoring a first portion of the modulated return radiation at a first distance from the sample;
monitoring a second portion of the modulated return radiation at a second distance from the sample;
processing the first and second portions of the modulated return radiation, using a predictive model, to determine a physiological characteristic of the sample;
wherein the predictive model is a multicriteria associative memory classifier.
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46. Apparatus for analyzing a sample, comprising:
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a source adapted to emit radiation that is directed at a sample to produce fluorescence from the sample, wherein the fluorescence is modulated by the sample;
a first sensor adapted to monitor the fluorescence at a first distance from the sample and generate a first signal indicative of the intensity of the fluorescence;
a second sensor adapted to monitor the fluorescence at a second distance from the sample and generate a second signal indicative of the intensity of the fluorescence, the second distance being different from the first distance; and
a processor associated with the first sensor and the second sensor and adapted to compare the first and second signals to each other to determine a modulation characteristic of the sample. - View Dependent Claims (47)
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48. Apparatus for analyzing a sample, comprising:
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a source adapted to emit radiation that is directed at a sample volume in a sample to produce fluorescence from the sample, such fluorescence including modulated fluorescence resulting from modulation by the sample;
a first sensor adapted to monitor the fluorescence at a first distance from the sample volume and generate a first signal indicative of the intensity of the fluorescence;
a second sensor adapted to monitor the fluorescence at a second distance from the sample volume and generate a second signal indicative of the intensity of the fluorescence, the second distance being different from the first distance;
anda processor associated with the first sensor and the second sensor and adapted to compare the first and second signals to each other to determine a modulation characteristic of the sample.
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49. Apparatus for determining a modulation characteristic of a biological material, comprising:
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a source adapted to emit excitation light;
a first waveguide disposed at a first distance from the sample adapted to transmit the excitation light from the light source to the biological material to cause the biological material to produce fluorescence, and adapted to collect a first portion of the fluorescence;
a first sensor, associated with the first waveguide, adapted to measure the intensity of the first portion of the fluorescence and generate a first signal indicative of the intensity of the first portion of the fluorescence;
a second waveguide disposed at a second distance from the sample adapted to collect a second portion of the fluorescence, the second distance being different from the first distance;
a second sensor, associated with the second waveguide, adapted to measure the intensity of the second portion of the fluorescence and generate a second signal indicative of the intensity of the second portion of the fluorescence;
anda processor adapted to compare the first and second signals to each other to determine a modulation characteristic of the biological material.
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50. Apparatus for analyzing a sample, comprising:
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a source adapted to emit radiation that is directed at a sample volume in a sample to produce fluorescence from the sample, such fluorescence including modulated fluorescence resulting from modulation by the sample;
a first sensor, displaced by a first distance from the sample volume adapted to monitor the fluorescence and generate a first signal indicative of the intensity of the fluorescence;
anda second sensor, displaced by a second distance from the sample volume adapted to monitor the fluorescence and generate a second signal indicative of the intensity of fluorescence, the second distance being different from the first distance;
anda processor associated with the first sensor and the second sensor and adapted to compare the first and second signals to each other to determine a physiological property of the sample.
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51. Apparatus for determining a physiological property of a biological material, comprising:
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a source adapted to emit excitation light;
a first waveguide disposed at a first distance from the sample, and adapted to transmit the excitation light from the light source to the biological material to cause the biological material to produce fluorescence, and further adapted to collect a first portion of the fluorescence;
a first sensor, associated with the first waveguide, for measuring the intensity of the first portion of the fluorescence and generating a first signal representative of the intensity of the first portion;
a second waveguide disposed at a second distance from the sample, and adapted to collect a second portion of the fluorescence, the second distance being different from the first distance;
a second sensor, associated with the first waveguide, for measuring the intensity of the second portion of the fluorescence and generating a second signal representative of the intensity of the second portion;
anda processor adapted to compare the first and second signals to each other to determine a physiological property of the biological material.
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52. A spectroscopic method of analyzing a sample, comprising:
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irradiating a sample with radiation to produce fluorescence from the sample, wherein the fluorescence is modulated by the sample;
monitoring a first portion of the modulated fluorescence at a first distance from the sample;
monitoring a second portion of the modulated fluorescence at a second distance from the sample, the second distance being different from the first distance;
comparing the first and second portions of the modulated fluorescence to each other to determine a modulation characteristic of the sample;
wherein the sample is a biological material tissue;
wherein the method further includes determining a physiological property of the tissue using the modulation characteristic; and
wherein the physiological property of the tissue is ischemia.
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53. A method for determining a physiological characteristic of a biological material, comprising:
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irradiating a sample of a biological material with radiation to produce fluorescence from the sample, wherein the fluorescence is modulated by the sample;
monitoring a first portion of the modulated fluorescence at a first distance from the sample;
monitoring a second portion of the modulated fluorescence at a second distance from the sample, the second distance being different from the first distance;
andcomparing the first and second portions of the modulated fluorescence to each other, using a predictive model, to determine a physiological characteristic of the sample;
,wherein the predictive model is multivariate.
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54. A spectroscopic method of analyzing a sample, comprising:
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irradiating a sample with radiation to produce fluorescence from the sample, wherein the fluorescence is modulated by the sample;
monitoring a first portion of the modulated fluorescence at a first angle from the sample; monitoring a second portion of the modulated fluorescence at a second angle from the sample; and comparing the first and second portions of the modulated fluorescence to each other to determine a modulation characteristic of the sample.
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Specification