Method for non-invasive measurement of an analyte

Claim 1

A method of measuring an analyte in a tissue of a subject comprising: (a) contacting the tissue with electromagnetic radiation having a first excitation wavelength, wherein the first excitation wavelength is substantially equal to an absorption wavelength of a temperature probe within the tissue, and wherein the temperature probe and the analyte are sufficiently proximate to one another that energy deposited into one by absorption of radiation is transferred to the other; (b) collecting the Raman spectra emitted by the tissue; and (c) analyzing the collected spectra to determine a concentration of the analyte present in the tissue.

Claim 2

A method of measuring an analyte in a tissue of a subject comprising: (a) contacting the tissue with electromagnetic radiation having a first excitation wavelength, wherein the first excitation wavelength is substantially equal to an absorption wavelength of a temperature probe within the tissue, and wherein the temperature probe and the analyte are sufficiently proximate to one another that energy deposited into one by absorption of radiation is transferred to the other; (b) collecting the Raman spectra emitted by the tissue; and (c) analyzing the collected spectra to determine a concentration of the analyte present in the tissue.

Claim 18

A method of measuring blood glucose in a subject comprising: (a) contacting tissue of the subject with electromagnetic radiation having a first excitation wavelength, wherein the first excitation wavelength is about 550 to about 400 nm, and wherein the tissue of the subject is in a blood replete state; (b) collecting Raman spectra emitted by the tissue in response to the first excitation wavelength, wherein the Raman spectra comprise Stokes and anti-Stokes spectra; (c) analyzing the spectra collected in step (b) to determine the spectra associated with hemoglobin; (d) contacting tissue of the subject with electromagnetic radiation having a second excitation wavelength, wherein the second excitation wavelength is about 9 to about 11 μm, and wherein the tissue of the subject is in a blood replete state; (e) collecting Raman spectra emitted by the tissue in response to the first and second excitation wavelengths, wherein the Raman spectra comprise Stokes and anti-Stokes spectra; (f) analyzing the spectra collected in step (e) to determine the spectra associated with hemoglobin; (g) repeating steps (a)-(f) while the tissue is in a blood depleted state; (h) determining net spectra emitted in response to the first and second excitation wavelengths, wherein the net spectra comprise the difference between the spectra obtained in the blood replete state and the blood depleted state; (i) determining the temperature shift between the temperature, in Kelvin, associated with Raman scattering emitted by hemoglobin in response to the first and second excitation wavelengths, and the temperature associated with Raman scattering emitted by hemoglobin in response to the first excitation wavelength in the absence of the second excitation wavelength; and (j) determining the concentration of glucose from the temperature shift determined in step (i).

Claim 19

A method of measuring blood glucose in a subject comprising: (a) contacting tissue of the subject with electromagnetic radiation having a first excitation wavelength, wherein the first excitation wavelength is about 550 to about 400 nm, and wherein the tissue of the subject is in a blood replete state; (b) collecting Raman spectra emitted by the tissue in response to the first excitation wavelength, wherein the Raman spectra comprise Stokes and anti-Stokes spectra; (c) analyzing the spectra collected in step (b) to determine the spectra associated with hemoglobin; (d) contacting tissue of the subject with electromagnetic radiation having a second excitation wavelength, wherein the second excitation wavelength is about 9 to about 11 μm, and wherein the tissue of the subject is in a blood replete state; (e) collecting Raman spectra emitted by the tissue in response to the first and second excitation wavelengths, wherein the Raman spectra comprise Stokes and anti-Stokes spectra; (f) analyzing the spectra collected in step (e) to determine the spectra associated with hemoglobin; (g) repeating steps (a)-(f) while the tissue is in a blood depleted state; (h) determining net spectra emitted in response to the first and second excitation wavelengths, wherein the net spectra comprise the difference between the spectra obtained in the blood replete state and the blood depleted state; (i) determining the temperature shift between the temperature, in Kelvin, associated with Raman scattering emitted by hemoglobin in response to the first and second excitation wavelengths, and the temperature associated with Raman scattering emitted by hemoglobin in response to the first excitation wavelength in the absence of the second excitation wavelength; and (j) determining the concentration of glucose from the temperature shift determined in step (i).

Claim 21

A method of measuring blood glucose in a subject comprising: (a) contacting tissue of the subject with electromagnetic radiation having a first excitation wavelength, wherein the first excitation wavelength is about 550 to about 400 nm, and wherein the tissue of the subject is in a blood replete state; (b) collecting Raman spectra emitted by the tissue, wherein the Raman spectra comprise anti-Stokes spectra; (c) analyzing the collected spectra to determine the spectra associated with glucose; (d) repeating steps (a)-(c) while the tissue is in a blood depleted state; and (e) determining net spectra emitted in response to the first excitation wavelength, wherein the net spectra comprise the difference between the spectra obtained in the blood replete state and the blood depleted state, to obtain a value representative of the concentration of glucose.

Claim 22

A method of measuring blood glucose in a subject comprising: (a) contacting tissue of the subject with electromagnetic radiation having a first excitation wavelength, wherein the first excitation wavelength is about 550 to about 400 nm, and wherein the tissue of the subject is in a blood replete state; (b) collecting Raman spectra emitted by the tissue, wherein the Raman spectra comprise anti-Stokes spectra; (c) analyzing the collected spectra to determine the spectra associated with glucose; (d) repeating steps (a)-(c) while the tissue is in a blood depleted state; and (e) determining net spectra emitted in response to the first excitation wavelength, wherein the net spectra comprise the difference between the spectra obtained in the blood replete state and the blood depleted state, to obtain a value representative of the concentration of glucose.

Claim 23

An apparatus for measuring an analyte in a tissue in a subject comprising: (a) a first light source that emits light having a first excitation wavelength that is substantially equal to an absorption wavelength of a temperature probe within the tissue; (b) a second light source that emits light having a second excitation wavelength that is substantially equal to an absorption wavelength of the analyte; (c) a detector that is disposed to receive Raman spectra scattered by the tissue in response to irradiation with the first and second excitation wavelengths and that produces output signals representative of the scattered Raman spectra; and (d) a computer coupled to receive the output signals produced by the detector that processes the output signals to derive a value indicative of the concentration of the analyte in the tissue from a comparison of output signals representative of the Raman spectra scattered in response to the first and second excitation wavelengths.

Claim 24

An apparatus for measuring an analyte in a tissue in a subject comprising: (a) a first light source that emits light having a first excitation wavelength that is substantially equal to an absorption wavelength of a temperature probe within the tissue; (b) a second light source that emits light having a second excitation wavelength that is substantially equal to an absorption wavelength of the analyte; (c) a detector that is disposed to receive Raman spectra scattered by the tissue in response to irradiation with the first and second excitation wavelengths and that produces output signals representative of the scattered Raman spectra; and (d) a computer coupled to receive the output signals produced by the detector that processes the output signals to derive a value indicative of the concentration of the analyte in the tissue from a comparison of output signals representative of the Raman spectra scattered in response to the first and second excitation wavelengths.