Veralight, Inc.

Inlight Solutions, Inc.

Rio Grande Medical Technologies, Inc.

Trutouch Technologies, Inc.

Medici Instruments LLC

Robert D Johnson

John D Maynard

Russell E Abbink

Marwood Neal Ediger

Edward L Hull

Christopher D Brown

Mark Ries Robinson

Trent D Ridder

Robert Kjell Rowe

Alan Ross

Michael Joseph Haass

Andrew D Meigs

Matthew Jarrod Novak

Stephen J Vanslyke

Steven T Strohl

M Ries Robinson

David J Nunez

Craig Gardner

Howland Jones

David Nuñez

William Gruner

Dashiell A Birnkrant

Howland D T Jones

The present invention provides methods and apparatuses for accurate noninvasive determination of tissue properties. Some embodiments of the present invention comprise an optical sampler having an illumination subsystem, adapted to communicate light having a first polarization to a tissue surface; a collection subsystem, adapted to collect light having a second polarization communicated from the tissue after interaction with the tissue; wherein the first polarization is different from the second polarization. The difference in the polarizations can discourage collection of light specularly reflected from the tissue surface, and can encourage preferential collection of light that has interacted with a desired depth of penetration or path length distribution in the tissue. The different polarizations can, as examples, be linear polarizations with an angle between, or elliptical polarizations of different handedness.

Methods and apparatuses for noninvasive determinations of analytes

Embodiments of the present invention provide an apparatus with a flexible probe suitable for determining properties of in vivo tissue from spectral information collected from various tissue sites. An illumination system provides light at a plurality of broadband ranges, which are communicated to a flexible optical probe. Light homogenizers and mode scramblers can be employed to improve the performance in some embodiments. The optical probe in some embodiments physically contacts the tissue, and in some embodiments does not physically contact the tissue. The optical probe receives light from the illumination system and transmits it to tissue, and receives light diffusely reflected in response to the broadband light, emitted from the in vivo tissue by fluorescence thereof in response to the broadband light, or a combination thereof. The optical probe can communicate the light to a spectrograph which produces a signal representative of the spectral properties of the light. An analysis system determines a property of the in vivo tissue from the spectral properties.

Determination of a measure of a glycation end-product or disease state using a flexible probe to determine tissue fluorescence of various sites

Embodiments of the present invention provide an apparatus suitable for determining properties of in vivo tissue from spectral information collected from various tissue sites. An illumination system provides light at a plurality of broadband ranges, which are communicated to an optical probe. The optical probe can be a flexible probe in some embodiments, allowing ease of application. Light homogenizers and mode scramblers can be employed to improve the performance in some embodiments. The optical probe in some embodiments physically contacts the tissue, and in some embodiments does not physically contact the tissue. The optical probe receives light from the illumination system and transmits it to tissue, and receives light diffusely reflected in response to the broadband light, emitted from the in vivo tissue by fluorescence thereof in response to the broadband light, or a combination thereof. The optical probe can communicate the light to a spectrograph which produces a signal representative of the spectral properties of the light. An analysis system determines a property of the in vivo tissue from the spectral properties.

Determination of a measure of a glycation end-product or disease state using tissue fluorescence of various sites

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. For example, the reflectance of the tissue can lead to errors if appropriate correction is not employed. The invention can also comprise a variety of models relating fluorescence to a measure of tissue state, including a variety of methods for generating such models. Other biologic information can be used in combination with the fluorescence properties to aid in the determination of a measure of tissue state. The invention also comprises apparatuses suitable for carrying out the method, including appropriate light sources, detectors, and models (for example, implemented on computers) used to relate detected fluorescence and a measure of tissue state.

Determination of a measure of a glycation end-product or disease state using tissue fluorescence preferentially from the dermis

Determination of a measure of a glycation end-product or disease state using tissue fluorescence

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.

Noninvasive determination of alcohol in tissue

Systems and methods for establishing and/or maintaining the accuracy of a multivariate calibration model designed for quantitative optical spectroscopic measurement of attributes or analytes in bodily tissues, bodily fluids or other biological samples, which are particularly useful when the spectral absorbance of the attribute or analyte is small relative to the background. The present invention provides an optically similar reference sample to reduce the effect of instrument or environment variation on the measurement capability of the model. The optically similar reference can be a gel composition having scattering particles suspended therein. The reference gel can be directly applied to a spectroscopic instrument sampler, or can be in a container specifically designed for optimal coupling to a spectroscopic instrument.

Optically similar reference samples

Systems and methods for establishing and/or maintaining the prediction capability over time of a multivariate calibration model designed for quantitative optical spectroscopic measurement of attributes or analytes in bodily tissues, bodily fluids or other biological samples, which are particularly useful when the spectral absorbance of the attribute or analyte is small relative to the background. The present invention provides an optically similar reference sample to capture the characteristics of instrument and environmental variation and to reduce the effect of such variation on the measurement capability of the model. The optically similar reference is preferably stable over time and is designed such that its optical properties are sufficiently matched to the sample of interest that instrument and environmental variations are captured in the same manner in both the test sample of interest and the optically similar reference sample. The optically similar reference sample may include one or more physical components which are spectroscopically measured in a manner which closely mimics the spectroscopic measurement of the test sample of interest. Spectral similarity may also be achieved by using alternative components with spectral characteristics similar to the components contained in the test sample of interest.

Optically similar reference samples and related methods for multivariate calibration models used in optical spectroscopy

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.

System for non-invasive measurement of glucose in humans

An illumination subsystem for use in optical analysis which provides spatially and angularly homogenized radiation to the sample being analyzed. The system eliminates the illumination system as an interferent in the overall optical analysis. Thus, modest translations or rotations of the illumination source or changing the illumination source does not require recalibration of the instrument or prior modeling of illumination variability due to such changes. Illumination stability is achieved by incorporating a light pipe which both angularly and spatially homogenizes the light. Further, a series of filters and/or lenses are incorporated to provide bandpass filtering which eliminates unwanted wavelengths or bands of wavelengths from contacting the tissue and allows for a higher signal-to-noise ratio when the sample is tissue, while preventing thermal damage.

Illumination device and method for spectroscopic analysis

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.

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Albuquerque, NM, United States of America

Robert D Johnson