Abstract: The invention provides a method and apparatus obtaining a hematocrit from a sample of in vivo tissue. The method comprises irradiating the sample with a single incident wavelength on a sample of tissue, simultaneously measuring wavelength shifted (IE) and unshifted (EE) light emitted from the tissue, and determining a relative volume of light emitted from two phases, wherein the two phases comprise a first Rayleigh and Mie scattering and fluorescent phase associated with red blood cells, and a second, non-scattering phase associated with plasma. The hematocrit is calculated from the volume of light emitted by the first phase relative to the total volume of light emitted from the first and second phases.

Abstract: The invention provides a method and apparatus obtaining a hematocrit from a sample of in vivo tissue. The method comprises irradiating the sample with a single incident wavelength on a sample of tissue, simultaneously measuring wavelength shifted (IE) and unshifted (EE) light emitted from the tissue, and determining a relative volume of light emitted from two phases, wherein the two phases comprise a first Rayleigh and Mie scattering and fluorescent phase associated with red blood cells, and a second, non-scattering phase associated with plasma. The hematocrit is calculated from the volume of light emitted by the first phase relative to the total volume of light emitted from the first and second phases.

Abstract: A calibrator suitable for calibrating a noninvasive analyte detector, such as a Raman spectroscopy device, allows the user of the detection device to establish standard measurements of the analyte to be detected, thereby providing assurance that appropriate analyte measurements are obtained at the time of sampling. The calibrator is simple to use, making it suitable for home use by individuals regardless of medical or technical skill level. In particular, the calibrator can be used with a noninvasive glucose detection system, such as for monitoring of blood glucose levels in diabetics. For use with noninvasive detectors designed for obtaining measurements from a subject's fingertip, the calibrator can be formed into a shape that reasonably mimics a fingertip in size, texture and/or spectral properties.

Abstract: Apparatus and methods for noninvasive spectroscopic measurement of an analyte in a subject that have been optimized for producing uniform and repeatable tissue modulation across test subjects and for the same test subject on different occasions are provided. The apparatus comprises an ergonomically shaped grip that substantially conforms to a subject's hand; a surface for placement of at least one of the subject's fingertips upon grasping the grip; and an optically transparent aperture, or a plurality of apertures, disposed within the surface. A modification to the surface of the apparatus adjacent to the aperture that is detectable via the tactile sense of the subject can be added to provide tactile feedback to the subject to guide correct placement of the fingertip over the aperture. The apparatus and methods can also incorporate feedback methods to guide and optimize placement and conditions of the fingertip to further improve accuracy of measurements.

Abstract: Disclosed are a device and methods for obtaining signals related to blood analytes and bone features by collecting spectra, such as fluorescence and Raman spectra, through the nail of a finger or toe. The invention additionally provides methods of modulating blood flow in a tissue of a subject.

Abstract: A calibrator suitable for calibrating a noninvasive analyte detector, such as a Raman spectroscopy device, allows the user of the detection device to establish standard measurements of the analyte to be detected, thereby providing assurance that appropriate analyte measurements are obtained at the time of sampling. The calibrator is simple to use, making it suitable for home use by individuals regardless of medical or technical skill level. In particular, the calibrator can be used with a noninvasive glucose detection system, such as for monitoring of blood glucose levels in diabetics. For use with noninvasive detectors designed for obtaining measurements from a subject's fingertip, the calibrator can be formed into a shape that reasonably mimics a fingertip in size, texture and/or spectral properties.

Abstract: Disclosed is a method for obtaining feedback to drive a servo system for aligning and maintaining alignment in optical systems that bring light to an in vivo skin sample, for adjusting the focus of the optical system, and for adjusting the net depth of focus of the optical system within the in vivo system under characterization. These methods comprise adjusting the angle of incidence of electromagnetic radiation and/or providing a shielding lens to block scattered incident light, or otherwise limiting the field of view of the Raman scattered radiation collection system to exclude optical surfaces of the excitation delivery portion of the optical system. In one embodiment, the method comprises discriminating between Raman signals originating on outer portions of skin from signals originating from substances deeper within the skin or other tissues. In another embodiment, the invention provides a method for detecting skin abnormalities and for assessing the aging of skin and related tissues.

Abstract: Disclosed are methods and materials for obtaining spatially resolved images of specific types of tissues. The method for imaging tissue comprises administering to the tissue a deuterated imaging agent and performing spectroscopy, preferably Raman spectroscopy. Electromagnetic radiation, such as a near infrared laser beam, is directed to a tissue of interest. The radiation can be scanned across and within the tissue of interest. When used in combination with a light collection system, it is possible to map out a specific volume of tissue, obtaining information regarding the distribution of specific endogenous chemical species. In some embodiments, specific imaging agents are employed to impart contrast between chemically different types of tissues.

Abstract: Disclosed is a method of modulating temperature of tissue in a subject to be spectroscopically probed. In a preferred embodiment, the method comprises applying a tissue modulation device of the invention to the tissue, passing current through the temperature regulating element so as to elevate or lower the temperature of the tissue, and passing electromagnetic radiation through the window of the device. Preferably, spectroscopic probing is performed when the temperature of the tissue has been elevated or lowered and when the temperature of the tissue is not elevated or lowered. The method can further comprise collecting Raman spectra emitted by the tissue. The invention also provides a method for determining phase transition, and a method for determining lipid content and identity and protein content and identity in a tissue of a subject.

Abstract: Disclosed is a method and apparatus for measuring an analyte in a tissue of a subject. The method comprises 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. 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. The Raman spectra emitted by the tissue are collected and analyzed to determine a concentration of analyte present in the tissue. The analysis can comprise measuring the Raman spectra associated with the temperature probe.

Abstract: Disclosed is a method for obtaining feedback to drive a servo system for aligning and maintaining alignment in optical systems that bring light to an in vivo skin sample, for adjusting the focus of the optical system, and for adjusting the net depth of focus of the optical system within the in vivo system under characterization. The invention additionally provides a method for obtaining feedback to drive a servo system for aligning and maintaining alignment in optical systems that collect light from an in vivo skin sample, and for adjusting the focus of the optical system. These methods comprise adjusting the angle of incidence of electromagnetic radiation and/or providing a shielding lens to block scattered incident light, or otherwise limiting the field of view of the Raman scattered radiation collection system to exclude optical surfaces of the excitation delivery portion of the optical system. Also provided is a method for identifying spectroscopic depth markers in tissues.

Abstract: Disclosed is a tissue modulation device for use dining spectroscopy of tissue of a subject. In one embodiment, the device comprises an inner sheath, an outer sheath and a window disposed through the inner and outer sheaths, wherein the inner and outer sheaths comprise a sufficiently flexible material that the device can be secured to a region of tissue to be spectroscopically probed, wherein the inner and outer sheaths are joined to one another so that at least one temperature regulating element can be disposed between the inner and outer sheaths, and wherein the window is sufficiently transparent that electromagnetic radiation can be delivered to and collected from an underlying tissue through the inner and outer sheaths. The invention additionally provides a method of modulating temperature of tissue in a subject to be spectroscopically probed.

Abstract: Methods are provided for noninvasively measuring blood volume and analyte concentration and for obtaining spectroscopic information relating to immobile tissues, such as skin. One method is for determining concentration of an analyte, such as glucose, in blood of a subject. The method comprises irradiating a region of tissue, such as a fingertip, of the subject with a light source; collecting fluorescence spectra emitted by the region of tissue, the quantity of fluorescence spectra being indicative of blood volume; and collecting Raman spectra emitted by the region of tissue at a wavelength range that corresponds to the analyte. The method further comprises dividing the collected Raman spectra by the collected fluorescence spectra to obtain a number proportional to the concentration of analyte per unit blood volume.

Abstract: Disclosed is a tissue modulation device comprising an upper surface and a lower surface, wherein the upper surface comprises a recessed region adjacent to a raised region, wherein the device is optically transparent in at least one of the recessed region or the raised region, wherein application of a first portion of a tissue to the raised region depresses the first portion of the tissue relative to a second portion of the tissue that is in apposition to the recessed region, and wherein the optically transparent region of the device is curved at the lower surface to substantially reduce backscattered light in a light path traveling through the optically transparent region to a light collection system. Also disclosed is a method of noninvasive spectroscopic measurement of an analyte in a subject.

Abstract: Disclosed is a method and apparatus for measuring an analyte in a tissue of a subject. The method comprises 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. 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. The Raman spectra emitted by the tissue are collected and analyzed to determine a concentration of analyte present in the tissue. The analysis can comprise measuring the Raman spectra associated with the temperature probe.