Non-invasive measurement of analytes
First Claim
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1. An in vivo method for monitoring the concentration of blood glucose, the method comprising:
- applying at least one small molecule metabolic reporter (SMMR) to at least one surface of skin for a predetermined period of time;
causing penetration of the at least one SMMR to a location having a depth corresponding to the stratum germinativum;
controlling a temperature at said location, wherein said controller increases blood flow to the dermal layer below said location;
monitoring a change in the stratum germinativum intracellular concentration of glucose in a metabolic pathway by detecting changes in the at least one SMMR at one or more time points using an optical reader; and
correlating the change in the stratum germinativum intracellular glucose concentration with in vivo blood glucose levels.
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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, apparatuses, 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 biologically active molecules found in skin.
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Citations
33 Claims
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1. An in vivo method for monitoring the concentration of blood glucose, the method comprising:
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applying at least one small molecule metabolic reporter (SMMR) to at least one surface of skin for a predetermined period of time; causing penetration of the at least one SMMR to a location having a depth corresponding to the stratum germinativum; controlling a temperature at said location, wherein said controller increases blood flow to the dermal layer below said location; monitoring a change in the stratum germinativum intracellular concentration of glucose in a metabolic pathway by detecting changes in the at least one SMMR at one or more time points using an optical reader; and correlating the change in the stratum germinativum intracellular glucose concentration with in vivo blood glucose levels. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14)
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- 15. An in vivo method for measuring blood glucose levels, said in vivo method comprising controlling a temperature at a population of stratum germinativum cells to increase blood flow to a dermal layer below said stratum germinativum cells, and monitoring intracellular glucose concentration in the population of stratum germinativum cells, wherein the monitoring comprises measuring the fluorescence spectrum emitted by at least one small molecule metabolic reporter (SMMR), wherein at least one fluorescence spectrum emitted by the at least one SMMR is stoichiometrically related to the glucose intracellular concentration in the population of stratum germinativum cells, whereby analyzing the relatedness provides the in vivo blood glucose level.
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24. A noninvasive method for monitoring in vivo blood glucose levels, the method comprising:
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applying at least one small molecule metabolic reporter (SMMR) to at least one surface of skin for a predetermined period of time; causing penetration of the at least one SMMR to a location corresponding to the stratum germinativum; contacting the at least one SMMR with one or more metabolites or analytes indicative of stratum germinativum intracellular glucose concentration; controlling a temperature at said location, wherein said controlling increases blood flow to the dermal layer below said location; monitoring a change in the stratum germinativum intracellular glucose concentration by detecting changes in the at least one SMMR using an optical reader, and correlating the change in the stratum germinativum intracellular glucose concentration with in vivo blood glucose levels. - View Dependent Claims (25, 26, 27, 28, 29, 30)
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31. A method for determining in vivo 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 mixture comprising at least one SMMR to the skin in a first controlled area such that the at least one SMMR resides in the stratum germinativum layer of the skin; applying a second mixture comprising at least one SMMR to the skin in a second controlled area; perturbing the second controlled area such that one or more extreme changes at the second controlled area are achieved; performing a calibration measurement on the perturbed area and recording the calibration data; performing a background measurement on an area of skin that has no SMMR and recording this background data; controlling a temperature at the first controlled area, wherein said controlling increases blood flow to a dermal layer below the first controlled area; illuminating the first controlled area with light and performing a first measurement on the first controlled area; detecting at least one wavelength spectrum of light reflected back from the first controlled area; performing at least a second measurement on the first controlled area at wavelengths suitable for each SMMR present; calculating at least one parameter from the response data to normalize the background data, calibration data and measurement data for the response using a spectrometer; calculating at least one parameter from the background data to correct the calibration data and measurement data for emission, absorption and scattering properties of the tissue; and calculating at least one stratum germinativum intracellular glucose parameter from the calibration data to relate the measurement data to the blood glucose concentration; thereby determining in vivo blood glucose concentration. - View Dependent Claims (32, 33)
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Specification