Non-invasive measurement of analytes
First Claim
1. A method for measuring in vivo blood glucose levels through the skin, said method comprising monitoring, in a population of cells one or more relevant metabolites, parameters or analytes in at least one metabolic pathway, wherein the monitoring comprises measuring the fluorescence spectrum emitted by a reporter composition located in the skin, wherein the fluorescence spectrum emitted by the reporter is stoichiometrically related to the metabolite, parameter or analyte concentration in the population of cells, whereby analyzing the relatedness provides the in vivo blood glucose level.
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Abstract
This invention provides devices, compositions and methods for determining the concentration of one or more metabolites or analytes in a biological sample, including cells, tissues, organs, organisms, and biological fluids. In particular, this invention provides materials, apparatus, and methods for several non-invasive techniques for the determination of in vivo blood glucose concentration levels based upon the in vivo measurement of one or more analytes or parameters found in skin.
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Citations
53 Claims
- 1. A method for measuring in vivo blood glucose levels through the skin, said method comprising monitoring, in a population of cells one or more relevant metabolites, parameters or analytes in at least one metabolic pathway, wherein the monitoring comprises measuring the fluorescence spectrum emitted by a reporter composition located in the skin, wherein the fluorescence spectrum emitted by the reporter is stoichiometrically related to the metabolite, parameter or analyte concentration in the population of cells, whereby analyzing the relatedness provides the in vivo blood glucose level.
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10. A skin sensor composition, comprising one or more of:
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a reporter dye and a marker dye;
ora dye exhibiting a wavelength shift in absorption or fluorescence emission in the presence of a metabolite;
wherein the skin composition is present at a depth from the surface of the skin from about 10 μ
m, wherein said depth corresponds with the bottom of the dead stratum corneum layer, to about 175 μ
m, wherein said depth corresponds with the top of the dermal layer, in the epidermis at an effective concentration for detection of one or more metabolites or analytes in a metabolic pathway in a subject or biological sample. - View Dependent Claims (11, 12, 13, 14, 15, 16, 17, 18, 19, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46)
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47. A method for determining blood glucose concentration, comprising the steps of:
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performing an instrument response measurement on a calibration target and recording the response data;
applying a dye mixture to the skin in a first small controlled spot such that the dye resides in the epidermal layer of the skin;
applying a second dye mixture to the skin in a second small controlled spot and perturbing the second spot such that one or more extreme changes that the mixture may undergo are achieved;
performing a calibration measurement on the perturbed spot and recording the calibration data;
performing a background measurement on an area of skin that has no dye and recording this background data;
performing a measurement on the first spot by illuminating the first spot with light;
detecting wavelength spectrum of light reflected back from the first spot;
performing further measurements on the first spot at wavelengths suitable for each dye present;
calculating a parameter from the response data to normalize the background, calibration and measurement data for the response of the spectrometer;
calculating a parameter from the background data to correct the calibration and measurement data for emission, absorption and scattering properties of the tissue;
calculating a metabolite parameter from the calibration data to relate the measurement data to the blood glucose concentration. - View Dependent Claims (48)
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49. A method of calculating a blood glucose concentration, said method comprising:
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measuring a background response and an autofluorescence tissue response from a calibration target comprising an epidermal layer of skin;
providing a first dye to a first skin location and causing residues of the first dye mixture to transfer into the epidermal layer of the skin;
providing a second dye to a second skin location and causing and recording at least one extreme change in the mixture;
illuminating the first skin location with a radiative emission;
detecting a resulting wavelength spectrum reflected from the first skin location;
optionally repeating the illuminating and detecting steps using irradiation and wavelength spectra associated with each dye provided; and
detecting at least one physico-chemical parameter that is related to the glycolytic pathway, wherein said parameter comprises a stoichiometric or highly correlated relationship with glucose concentration;
thereby determining the blood glucose concentration. - View Dependent Claims (50, 51, 53)
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52. A method for determining the concentration of at least one metabolite or analyte in skin tissue, the method comprising:
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(a) administering to the skin tissue a small molecule metabolite reporter (SMMR) agent;
(b) causing penetration of the SMMR agent to a region of the skin at a depth between the dermis and the epidermis, wherein the depth from the surface of the skin is from about 10 μ
m, wherein said depth corresponds with the bottom of the dead stratum corneum layer, to about 175 μ
m, wherein said depth corresponds with the top of the dermal layer;
(c) irradiating the SMMR agent in the skin tissue with a source of electromagnetic radiation;
(d) measuring the fluorescence spectra emitted from the SMMR agent; and
(e) analyzing the emitted fluorescence spectra;
wherein the analysis will result in a determination of the concentration of the metabolite or analyte.
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Specification