Abstract: A confocal inspection system can optically characterize a sample. An objective lens, or separate incident and return lenses, can deliver incident light from a light source to the sample, and can collect light from the sample. Confocal optics can direct the collected light onto a detector. The system can average the incident light over multiple locations at the sample, for example, by scanning the incident light with a pivotable mirror in the incident and return optical paths, or by illuminating and collecting with multiple spaced-apart confocal apertures. The system can average the collected light, for example, by directing the collected light onto a single-pixel detector, or by directing the collected light onto a multi-pixel detector and averaging the pixel output signals to form a single electronic signal. Averaging the incident and/or return light can be advantageous for structured or inhomogeneous samples.

Abstract: A confocal inspection system can optically characterize a sample. An objective lens, which can be a single lens or a combination of separate illumination and collection lenses, can have a pupil. The objective lens can deliver incident light to the sample through an annular illumination region of the pupil, and can collect scattered light returning from the sample to form collected light. Confocal optics can be positioned to receive the collected light. A detector can be configured with the confocal optics so that the detector generates signals from light received from a specified depth at or below a surface of the sample and rejects signals from light received from depths away from the specified depth. An optical element, such as a mask, a reconfigurable panel, or the detector, can define the annular collection region to be non-overlapping with the annular illumination region in the pupil.

Abstract: A confocal inspection system can optically characterize a sample. An objective lens, or separate incident and return lenses, can deliver incident light from a light source to the sample, and can collect light from the sample. Confocal optics can direct the collected light onto a detector. The system can average the incident light over multiple locations at the sample, for example, by scanning the incident light with a pivotable mirror in the incident and return optical paths, or by illuminating and collecting with multiple spaced-apart confocal apertures. The system can average the collected light, for example, by directing the collected light onto a single-pixel detector, or by directing the collected light onto a multi-pixel detector and averaging the pixel output signals to form a single electronic signal. Averaging the incident and/or return light can be advantageous for structured or inhomogeneous samples.

Abstract: A confocal inspection system can optically characterize a sample. An objective lens, which can be a single lens or a combination of separate illumination and collection lenses, can have a pupil. The objective lens can deliver incident light to the sample through an annular illumination region of the pupil, and can collect scattered light returning from the sample to form collected light. Confocal optics can be positioned to receive the collected light. A detector can be configured with the confocal optics so that the detector generates signals from light received from a specified depth at or below a surface of the sample and rejects signals from light received from depths away from the specified depth. An optical element, such as a mask, a reconfigurable panel, or the detector, can define the annular collection region to be non-overlapping with the annular illumination region in the pupil.

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 various light excitation and detection configurations. 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. 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.

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: 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: A method of determining 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 Raman scattering of a chemical with the tissue responsive to the excitation light is detected. The detected light can be combined with a model relating Raman emission with disease state to determine a disease state of the individual. 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 Raman emission of a chemical in the tissue. For example, the reflectance of the tissue can lead to errors if appropriate correction is not employed.

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: 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.

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: 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: 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.

Abstract: An apparatus and method for infrared spectral analysis of samples to determine if the samples are normal or abnormal or to otherwise classify the sample. More specifically, the apparatus and method classify the sample on the basis of attenuation of infrared radiation at different wavelengths using a within-sample variance model. Further, the method and apparatus can include merging the output of multivariate classification models with the within-sample variance model applied to the infrared spectra sample such that their combined output results in a classification accuracy that is greater than any single model. The invention is useful in classifying, for example, biological samples such as human tissue, including cervical cells.