Abstract: A system and method for determining the pH of tissue in vivo. A Raman spectrometer is used to collect Raman spectra from the target tissue. The Raman spectra are baseline subtracted and assessed to determine the concentration of HPO4?2 and H2PO4?1 for the purposes of calculating the pH. The approach was validate in vitro using PBS solutions of known pH. The approach was confirmed in vivo using rat and swine models by probing the immediate vicinity of a contusive spinal cord injury (SCI) in the first minutes and hours after injury. Using a dynamic analysis and the Henderson-Hasselbalch equation, the average of (N=12) noninvasive Raman-based pH measurements of CSF was 7.073±0.156 and at >95% confidence there is no statistically significant difference between the Raman-based and the physically sampled results.

Abstract: The invention provides a method of determining turbidity and concentration simultaneously a sample by irradiating the sample with a single incident wavelength and simultaneously measuring wavelength shifted (IE) and unshifted (EE) light emitted. A relative volume of light emitted from two phases may be determined, wherein the two phases comprise a first Rayleigh and Mie scattering and fluorescent phase associated with suspended particles, and a second, non-scattering but fluorescent phase associated with suspending solution. Volumes of the phases and/or concentrations of specific fluorophores or Raman active species are 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 system and method for determining the pH of tissue in vivo. A Raman spectrometer is used to collect Raman spectra from the target tissue. The Raman spectra are baseline subtracted and assessed to determine the concentration of HPO4?2 and H2PO4?1 for the purposes of calculating the pH. The approach was validate in vitro using PBS solutions of known pH. The approach was confirmed in vivo using rat and swine models by probing the immediate vicinity of a contusive spinal cord injury (SCI) in the first minutes and hours after injury. Using a dynamic analysis and the Henderson-Hasselbalch equation, the average of (N=12) noninvasive Raman-based pH measurements of CSF was 7.073±0.156 and at >95% confidence there is no statistically significant difference between the Raman-based and the physically sampled results.

Abstract: A system and method for obtaining the intravascular plasma volume, red blood cell volume, oxygen saturation SpO2 and Hgb hemoglobin concentration from a sample of in vivo tissue. A sample is irradiated with pulses of single incident wavelength light on a sample of tissue. The prompt emission (PE) and the delayed (DE) light emitted from the tissue are measured simultaneously. A relative volume of light emitted from two phases contained within the tissue is then determined, 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 plasma volume, Hct, Hgb and SpO2 is calculated from the relative volume of light emitted by the first phase and the relative volume of light emitted from the second phase differentiated by state of oxygenation.

Abstract: The invention provides a method of determining turbidity and concentration simultaneously a sample by irradiating the sample with a single incident wavelength and simultaneously measuring wavelength shifted (IE) and unshifted (EE) light emitted. A relative volume of light emitted from two phases may be determined, wherein the two phases comprise a first Rayleigh and Mie scattering and fluorescent phase associated with suspended particles, and a second, non-scattering but fluorescent phase associated with suspending solution. Volumes of the phases and/or concentrations of specific fluorophores or Raman active species are 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 of determining turbidity and concentration simultaneously a sample by irradiating the sample with a single incident wavelength and simultaneously measuring wavelength shifted (IE) and unshifted (EE) light emitted. A relative volume of light emitted from two phases may be determined, wherein the two phases comprise a first Rayleigh and Mie scattering and fluorescent phase associated with suspended particles, and a second, non-scattering but fluorescent phase associated with suspending solution. Volumes of the phases and/or concentrations of specific fluorophores or Raman active species are 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: 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: Described is a method to determine the viability of cells by measuring the absolute and relative rate of metabolic activity and/or integrity of the cell membrane through the use of vibrational spectroscopy. The use of deuterated agents facilitates detection of changes associated with a change in viability.

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 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: 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: Tungsten and molybdenum oxide, and oxides of other metals and bronzes derived from such oxides, constitute a broad class of materials having applications as photochromic sunblock/cosmetics. These materials are well known in the prior art in the context of photochromic optical data storage media and they offer an excellent match with the very properties needed for cosmetic applications. The invention relates to the adaptation of the class of tungsten and molybdenum oxide photochromics to sunblocking/dosimetry, energy storage, and cosmetic coloration. In addition, certain naturally occurring proteins which exhibit the necessary photochromism can also be used alone for the same purpose or with the oxide systems described above.

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 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.