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; 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.
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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.
87 Citations
65 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; 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. - 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, 30, 31, 32, 33, 34)
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35. The method of claim 35, wherein the wavelength that is strongly absorbed by glucose is substantially in the range of 1550 to 1700 nm, and the wavelength lightly absorbed by glucose is substantially in the range of 1350 to 1430 nm.
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36. 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 different 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;
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. - View Dependent Claims (37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64)
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65. An apparatus for non-invasive measurement of a concentration of a target analyte in a fluid within a sample matrix, comprising:
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means for 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 wavelengh pair;
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 different amount of fluid within the sample;
means for detecting a portion of the combined beam that is transmitted through or reflected by the sample while the amount of fluid in the sample varies to generate a time-varying output signal proportional to the intensity of the combined beam at each of the two repetitive periods of radiation of at least one wavelength pair;
means for obtaining a time-varying estimate of the amount of fluid in the sample while the amount of fluid in the sample varies; and
means for processing the measured output signal from the sample detector and 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.
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Specification