Abstract: An apparatus and method for non-invasive determination of attributes of human tissue by quantitative infrared spectroscopy. The system includes subsystems optimized to contend with the complexities of the tissue spectrum, high signal-to-noise ratio and photometric accuracy requirements, tissue sampling errors, calibration maintenance problems, and calibration transfer problems. The subsystems include an illumination subsystem, a tissue sampling subsystem, a spectrometer subsystem, a data acquisition subsystem, and a processing subsystem. The invention is applicable, as examples, to determining the concentration or change of concentration of alcohol in human tissue.

Abstract: The present invention provides improved methods and apparatuses for accurate measurements using interferometers. A functional relationship between the optical path difference and time is determined from a reference signal from an interferometer. The times at which the interferometer had specific optical path differences can be determined from the functional relationship. Those times can then be used to select times at which the spectroscopic signal from the interferometer was produced at the specific optical path differences. The invention can be applied, as examples, to maintain instrument calibration, and to transfer or compare calibrations or measurements across different interferometers.

Abstract: The present invention provides methods and apparatuses that can improve measurement accuracy in interferometers. The invention provides methods for determining digital compensation filters that measure a frequency response or responses to be compensated, and then determining a filter target response from the inverse of the frequency response or responses. A digital compensation filter can be determined from the filter target response using a discrete sum of cosines with a phase argument. The invention also allows other desired filter responses to be integrated into the filter target response before determining the digital compensation filter.

Abstract: A method of determining a measure of a tissue state (e.g., glycation end-product or disease state) in an individual. A portion of the tissue of the individual is illuminated with excitation light, then light emitted by the tissue due to fluorescence of a chemical with the tissue responsive to the excitation light is detected. The detected light can be combined with a model relating fluorescence with a measure of tissue state to determine a tissue state. The invention can comprise single wavelength excitation light, scanning of excitation light (illuminating the tissue at a plurality of wavelengths), detection at a single wavelength, scanning of detection wavelengths (detecting emitted light at a plurality of wavelengths), and combinations thereof. The invention also can comprise correction techniques that reduce determination errors due to detection of light other than that from fluorescence of a chemical in the tissue.

Abstract: Methods and apparatuses of determining the pH of a sample. A method can comprise determining an infrared spectrum of the sample, and determining the hemoglobin concentration of the sample. The hemoglobin concentration and the infrared spectrum can then be used to determine the pH of the sample. In some embodiments, the hemoglobin concentration can be used to select an model relating infrared spectra to pH that is applicable at the determined hemoglobin concentration. In other embodiments, a model relating hemoglobin concentration and infrared spectra to pH can be used. An apparatus according to the present invention can comprise an illumination system, adapted to supply radiation to a sample; a collection system, adapted to collect radiation expressed from the sample responsive to the incident radiation; and an analysis system, adapted to relate information about the incident radiation, the expressed radiation, and the hemoglobin concentration of the sample to pH.

Abstract: An apparatus and method for non-invasive measurement of glucose in human tissue by quantitative infrared spectroscopy to clinically relevant levels of precision and accuracy. The system includes six subsystems optimized to contend with the complexities of the tissue spectrum, high signal-to-noise ratio and photometric accuracy requirements, tissue sampling errors, calibration maintenance problems, and calibration transfer problems. The six subsystems include an illumination subsystem, a tissue sampling subsystem, a calibration maintenance subsystem, an FTIR spectrometer subsystem, a data acquisition subsystem, and a computing subsystem.

Abstract: The present invention provides methods and devices for using feedback to improve non-invasive tissue measurements by making measurements faster, easier to perform, and less error prone. In some embodiments, a set of metrics is identified as measurable potential sources of measurement error that can be controlled by a user. In some embodiments, the set of metrics can be analyzed to determine which metrics are related to one another, and some possible error metrics can be discarded, and others used as surrogate metrics for measuring and monitoring measurement errors.

Abstract: Methods and apparatuses of determining the pH of a sample. A method can comprise determining an infrared spectrum of the sample, and determining the hemoglobin concentration of the sample. The hemoglobin concentration and the infrared spectrum can then be used to determine the pH of the sample. In some embodiments, the hemoglobin concentration can be used to select an model relating infrared spectra to pH that is applicable at the determined hemoglobin concentration. In other embodiments, a model relating hemoglobin concentration and infrared spectra to pH can be used. An apparatus according to the present invention can comprise an illumination system, adapted to supply radiation to a sample; a collection system, adapted to collect radiation expressed from the sample responsive to the incident radiation; and an analysis system, adapted to relate information about the incident radiation, the expressed radiation, and the hemoglobin concentration of the sample to pH.

Abstract: An optical sampling subsystem and method that reduces the effect of errors in an optical sampling subsystem when heterogeneously distributed samples are measured in the path of a spectrometer. The optical sampling subsystem is used to collect the non-uniformly distributed radiation exiting the heterogeneous sample and produce a uniform irradiance at its output. The output is then directed into the wavenumber (inverse of wavelength in centimeters) dispersive or modulating device of the spectrometer. The resulting spectra exhibit less spectral complexity arising from components of the sampling subsystem design and the heterogeneous sample, in particular, the effect of wavenumber shift is minimized. Improved quantitative predictions, qualitative analysis and calibration transfer are direct consequences of the reduced spectral complexity.

Abstract: A vertical cavity surface-emitting laser (VCSEL) package utilized as a laser reference for use in interferometry. The primary disadvantage of VCSELs, in terms of interferometry, has been found to be the relatively poor wavenumber stability of the beam. The present invention is a method and apparatus that makes viable a VCSEL package suitable for use as a reference in interferometry. The VCSEL package incorporates current control, temperature control and an algorithm for correcting wavenumber drift. The algorithm is derived from spectroscopic analysis of a reference sample having a known spectrum and comparing the generated spectrum to the known spectrum.

Abstract: An optical sampling subsystem and method that reduces the effect of errors in an optical sampling subsystem when heterogeneously distributed samples are measured in the path of a spectrometer. The optical sampling subsystem is used to collect the non-uniformly distributed radiation exiting the heterogeneous sample and produce a uniform irradiance at its output. The output is then directed into the wavenumber (inverse of wavelength in centimeters) dispersive or modulating device of the spectrometer. The resulting spectra exhibit less spectral complexity arising from components of the sampling subsystem design and the heterogeneous sample, in particular, the effect of wavenumber shift is minimized. Improved quantitative predictions, qualitative analysis and calibration transfer are direct consequences of the reduced spectral complexity.

Abstract: A vertical cavity surface-emitting laser (VCSEL) package utilized as a laser reference for use in interferometry. The primary disadvantage of VCSELs, in terms of interferometry, has been found to be the relatively poor wavenumber stability of the beam. The present invention is a method and apparatus that makes viable a VCSEL package suitable for use as a reference in interferometry. The VCSEL package incorporates current control, temperature control and an algorithm for correcting wavenumber drift. The algorithm is derived from spectroscopic analysis of a reference sample having a known spectrum and comparing the generated spectrum to the known spectrum.

Abstract: An apparatus and method for non-invasive measurement of glucose in human tissue by quantitative infrared spectroscopy to clinically relevant levels of precision and accuracy. The system includes six subsystems optimized to contend with the complexities of the tissue spectrum, high signal-to-noise ratio and photometric accuracy requirements, tissue sampling errors, calibration maintenance problems, and calibration transfer problems. The six subsystems include an illumination subsystem, a tissue sampling subsystem, a calibration maintenance subsystem, an FTIR spectrometer subsystem, a data acquisition subsystem, and a computing subsystem.

Abstract: An apparatus and method for non-invasive measurement of glucose in human tissue by quantitative infrared spectroscopy to clinically relevant levels of precision and accuracy. The system includes six subsystems optimized to contend with the complexities of the tissue spectrum, high signal-to-noise ratio and photometric accuracy requirements, tissue sampling errors, calibration maintenance problems, and calibration transfer problems. The six subsystems include an illumination subsystem, a tissue sampling subsystem, a calibration maintenance subsystem, an FTIR spectrometer subsystem, a data acquisition subsystem, and a computing subsystem.