Non-invasive substance concentration measurement using and optical bridge
First Claim
1. A method of non-invasive measurement of a concentration of a target analyte in a fluid within a sample matrix, the method comprising the steps of:
- directing a combined beam of electromagnetic radiation at the sample, the combined beam including at least two repetitive periods of radiation having different wavelengths, the target analyte having different absorption coefficients for two of the different wavelengths, the two wavelengths forming a wavelength pair;
while the sample is at a first sample fluid state having an initial amount of fluid, detecting the combined beam with a sample detector arranged to detect a portion of the radiation transmitted through or reflected by the sample to generate an output signal proportional to the intensity of the combined beam at each of the two repetitive periods of radiation of the wavelength pair;
subjecting the sample to a second sample fluid state to change the amount of fluid within the sample;
measuring the output signal of the sample detector and obtaining an estimate of the amount of fluid in the sample while the amount of fluid in the sample varies from the initial amount in the first fluid state to a second amount in the second fluid state; and
combining the measured output signal from the sample detector with the estimate of the amount of the fluid containing the target analyte to produce an estimate of the concentration of the analyte in the fluid;
wherein during one of the sample fluid states, the detected intensities at each of the at least two repetitive periods of radiation are made substantially equal by adjusting the intensity of at least one of the repetitive periods of radiation entering the sample.
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Accused Products
Abstract
An improved method for non-invasively measuring a concentration of a target analyte dissolved in a fluid flowing through a sample is presented. It includes directing a probe beam of electromagnetic radiation, consisting of time multiplexed components of different wavelengths, through the sample and measuring the difference of the absorption of the radiation at at least one wavelength pair at different sample states. During sample state changes, the amount of fluid containing the target analyte within the sample is changing, which varies the total amount of target analyte in the sample, as well as the absorption properties of the sample. The sample states are produced, for instance, by compressing and uncompressing the tissue sample. The accuracy of the presented method is enhanced by including continuous estimation of the amount of the fluid containing the target analyte within the sample, and measurement of the variations of the absorption at a wavelength at which the target analyte absorbs significantly. The method is particularly useful in measuring the concentration of a target analyte, such as glucose, in tissue containing blood. An apparatus for performing this method also is disclosed.
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Citations
76 Claims
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1. A method of non-invasive measurement of a concentration of a target analyte in a fluid within a sample matrix, the method comprising the steps of:
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directing a combined beam of electromagnetic radiation at the sample, the combined beam including at least two repetitive periods of radiation having different wavelengths, the target analyte having different absorption coefficients for two of the different wavelengths, the two wavelengths forming a wavelength pair; while the sample is at a first sample fluid state having an initial amount of fluid, detecting the combined beam with a sample detector arranged to detect a portion of the radiation transmitted through or reflected by the sample to generate an output signal proportional to the intensity of the combined beam at each of the two repetitive periods of radiation of the wavelength pair; subjecting the sample to a second sample fluid state to change the amount of fluid within the sample; measuring the output signal of the sample detector and obtaining an estimate of the amount of fluid in the sample while the amount of fluid in the sample varies from the initial amount in the first fluid state to a second amount in the second fluid state; and combining the measured output signal from the sample detector with the estimate of the amount of the fluid containing the target analyte to produce an estimate of the concentration of the analyte in the fluid;
wherein during one of the sample fluid states, the detected intensities at each of the at least two repetitive periods of radiation are made substantially equal by adjusting the intensity of at least one of the repetitive periods of radiation entering 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)
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25. A method of non-invasive measurement of a concentration of a target analyte in a fluid within a sample matrix, the method comprising the steps of:
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directing a combined beam of electromagnetic radiation at the sample, the combined beam including at least two repetitive periods of radiation having different wavelengths, the target analyte having different absorption coefficients for two of the different wavelengths, the two wavelengths forming a wavelength pair; while the sample is at a first sample fluid state having an initial amount of fluid, detecting the combined beam with a sample detector arranged to detect a portion of the radiation transmitted through or reflected by the sample to generate an output signal proportional to the intensity of the combined beam at each of the two repetitive periods of radiation of the wavelength pair; subjecting the sample to a second sample fluid state to change the amount of fluid within the sample; measuring the output signal of the sample detector and obtaining an estimate of the amount of fluid in the sample while the amount of fluid in the sample varies from the initial amount in the first fluid state to a second amount in the second fluid state; and combining the measured output signal from the sample detector with the estimate of the amount of the fluid containing the target analyte to produce an estimate of the concentration of the analyte in the fluid, wherein the wavelengths of the wavelength pair are selected to minimize the detected transmission or reflection difference between the wavelength periods measured during a sample state.
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26. A method of non-invasive measurement of a concentration of a target analyte in a fluid within a sample matrix, the method comprising the steps of:
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directing a combined beam of electromagnetic radiation at the sample, the combined beam including at least two repetitive periods of radiation having different wavelengths, the target analyte having different absorption coefficients for two of the different wavelengths, the two wavelengths forming a wavelength pair; while the sample is at a first sample fluid state having an initial amount of fluid, detecting the combined beam with a sample detector arranged to detect a portion of the radiation transmitted through or reflected by the sample to generate an output signal proportional to the intensity of the combined beam at each of the two repetitive periods of radiation of the wavelength pair; subjecting the sample to a second sample fluid state to change the amount of fluid within the sample; measuring the output signal of the sample detector and obtaining an estimate of the amount of fluid in the sample while the amount of fluid in the sample varies from the initial amount in the first fluid state to a second amount in the second fluid state; and combining the measured output signal from the sample detector with the estimate of the amount of the fluid containing the target analyte to produce an estimate of the concentration of the analyte in the fluid, wherein the intensities of the periods of radiation are adjusted when the sample is at a first sample fluid state, and at least one of the wavelengths of the at least two repetitive periods of radiation is selected to minimize the detected transmission or reflection difference when the sample is at a state different from the first state. - View Dependent Claims (27)
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28. A method of non-invasive measurement of a concentration of a target analyte in a fluid within a sample matrix, the method comprising the steps of:
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directing a combined beam of electromagnetic radiation at the sample, the combined beam including at least two repetitive periods of radiation having different wavelengths, the target analyte having different absorption coefficients for two of the different wavelengths, the two wavelengths forming a wavelength pair; while the sample is at a first sample fluid state having an initial amount of fluid, detecting the combined beam with a sample detector arranged to detect a portion of the radiation transmitted through or reflected by the sample to generate an output signal proportional to the intensity of the combined beam at each of the two repetitive periods of radiation of the wavelength pair; subjecting the sample to a second sample fluid state to change the amount of fluid within the sample; measuring the output signal of the sample detector and obtaining an estimate of the amount of fluid in the sample while the amount of fluid in the sample varies from the initial amount in the first fluid state to a second amount in the second fluid state; and combining the measured output signal from the sample detector with the estimate of the amount of the fluid containing the target analyte to produce an estimate of the concentration of the analyte in the fluid, wherein the start of a sample fluid state variation is synchronized to a pulsation of the sample fluid. - View Dependent Claims (29, 30, 31, 32, 33, 34)
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35. An apparatus for non-invasively measuring a concentration of a target analyte in a fluid within a sample, comprising:
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a source for generating a combined beam of electromagnetic radiation including at least two repetitive periods of radiation having different wavelengths, at least two of the wavelengths having different absorption coefficients for the target analyte; a mount for positioning a sample within an optical path of the combined beam; means for controlling the amount of fluid within the sample to maintain a first sample fluid state with an initial amount of fluid within the sample, followed by a second sample fluid state with a second amount of fluid within the sample; a sample detector arranged to detect a portion of the combined beam transmitted through or reflected by the sample, the sample detector generating an output signal proportional to the detected intensity of the combined beam at each of the two repetitive periods of radiation; means for obtaining an estimate of the amount of the fluid in the sample while the amount of fluid in the sample varies from the initial amount in the first fluid state to a second amount in the second fluid state; a processor for controlling the measurement sequence and combining the measured output signal from the sample detector with the estimate of the amount of fluid, to produce an estimate of the concentration of the target analyte in the fluid; and means for measuring a phase of pulsation of the fluid within the matrix. - View Dependent Claims (36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57)
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58. An apparatus for non-invasively measuring a concentration of a target analyte in a fluid within a sample, comprising:
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a source for generating a combined beam of electromagnetic radiation including at least two repetitive periods of radiation having different wavelengths, at least two of the wavelengths having different absorption coefficients for the target analyte; a mount for positioning a sample within an optical path of the combined beam; means for controlling the amount of fluid within the sample to maintain a first sample fluid state with an initial amount of fluid within the sample, followed by a second sample fluid state with a second amount of fluid within the sample; a sample detector arranged to detect a portion of the combined beam transmitted through or reflected by the sample, the sample detector generating an output signal proportional to the detected intensity of the combined beam at each of the two repetitive periods of radiation; means for obtaining an estimate of the amount of the fluid in the sample while the amount of fluid in the sample varies from the initial amount in the first fluid state to a second amount in the second fluid state; a processor for controlling the measurement sequence and combining the measured output signal from the sample detector with the estimate of the amount of fluid, to produce an estimate of the concentration of the target analyte in the fluid; and means for synchronizing the start of a change in sample state to the phase of pulsation of the fluid within the sample. - View Dependent Claims (59, 60, 61)
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62. An apparatus for non-invasively measuring a concentration of a target analyte in a fluid within a sample, comprising:
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a source for generating a combined beam of electromagnetic radiation including at least two repetitive periods of radiation having different wavelengths, at least two of the wavelengths having different absorption coefficients for the target analyte; a mount for positioning a sample within an optical path of the combined beam; means for controlling the amount of fluid within the sample to maintain a first sample fluid state with an initial amount of fluid within the sample, followed by a second sample fluid state with a second amount of fluid within the sample; a sample detector arranged to detect a portion of the combined beam transmitted through or reflected by the sample, the sample detector generating an output signal proportional to the detected intensity of the combined beam at each of the two repetitive periods of radiation; means for obtaining an estimate of the amount of the fluid in the sample while the amount of fluid in the sample varies from the initial amount in the first fluid state to a second amount in the second fluid state; a processor for controlling the measurement sequence and combining the measured output signal from the sample detector with the estimate of the amount of fluid, to produce an estimate of the concentration of the target analyte in the fluid, wherein one of the wavelengths of the at least two repetitive periods of radiation is selected to minimize the intensity of the detected transmission or reflection difference between the wavelength periods in one of the sample states.
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63. A system for non-invasive measurement of a concentration of a target analyte in a fluid within a sample matrix, comprising:
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an optical bridge measurement device which generates an output signal indicative of the differential optical absorption in the sample between two or more radiation beams having different wavelengths, the target analyte having different absorption coefficients for two of the different wavelengths; a fluid variation device which varies the amount of fluid within the sample between an initial amount and a second amount; a fluid content estimation device which generates an output signal indicative of the amount of fluid in the sample; and a measurement device which records the output of the optical bridge device and the output of the fluid content estimation device multiple times while the amount of fluid varies between the initial amount and the second amount. - View Dependent Claims (64, 65, 66, 67, 68, 69)
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70. A method for non-invasive measurement of a concentration of a target analyte in a fluid within a sample matrix, comprising:
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varying the amount of fluid within the sample between an initial amount and a second amount; recording the output of an optical bridge measurement device multiple times while the amount of fluid varies between the initial amount and the second amount; and recording an estimate of the fluid content in the sample multiple times while the amount of fluid varies between the initial amount and the second amount. - View Dependent Claims (71, 72, 73, 74, 75, 76)
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Specification