Abstract: An apparatus and method for reproducibly interfacing a living tissue sample to the measurement probe of a spectrometer instrument in-situ minimizes spectral interference related to sampling variations. A minimal contact subject interface includes supports replaceably mounted on a base. An optical coupling means, such as a fiber optic probe, contacts the measurement site through a probe aperture in the base. During use, a subject rests an extremity on the support elements, so that the extremity is reproducibly positioned and supported in relation to the optical coupling means. The supports have a small contact area, minimizing contact with the skin at the measurement site. The interface module is adjustable to fit any subject. By reproducibly positioning and supporting the body appendage using minimal contact supports, spectral interference due to variations in placement, applied pressure, and temperature transients secondary to contact with the interface module are greatly minimized.

Abstract: A non-invasive system for characterizing and classifying the state and structure of a tissue sample operates on a near infrared absorbance spectrum of in vivo tissue. A method that uses near-infrared spectral measurements to characterize and classify the state and structure of tissue sampled based on absorbance features related to fat in adipose tissue is provided. Also provided is a method of estimating skin fold thickness. The approach provides information about sources of tissue variability and is therefore useful for establishing the general category of the tissue structure. Categorization of subjects on the basis of the determination is suitable for further spectral analysis and the measurement of biological and chemical compounds, such as blood analytes. The invention further provides a method of estimating percent body fat based on a skin fold thickness estimate.

Abstract: Instrumentation and procedures for noninvasively determining the sex of human and animal subjects in vivo have been developed based on the irradiation of skin tissue with near infrared light. The method of sex determination provides additional information about primary sources of systematic tissue variability, namely, the thickness of the dermis and the subcutaneous fat. Categorization of subjects on the basis of the determination is therefore suitable for further spectral analysis and the measurement of biological and chemical compounds, such as blood analytes.

Abstract: The invention provides a class of samples that model the human body. This family of samples is based upon emulsions of oil in water with lecithin acting as the emulsifier. These solutions that have varying particle sizes may be spiked with basis set components (albumin, urea and glucose) to simulate skin tissues further. The family of samples is such that other organic compounds such as collagen, elastin, globulin and bilirubin may be added, as can salts such as Na+, K+ and Cl−. Layers of varying thickness with known index of refraction and particle size distributions may be generated using simple crosslinking reagents, such as collagen (gelatin). The resulting samples are flexible in each analyte's concentration and match the skin layers of the body in terms of the samples reduced scattering and absorption coefficients, &mgr;ms and &mgr;ma. This family of samples is provided for use in the medical field where lasers and spectroscopy based analyzers are used in treatment of the body.

Abstract: An apparatus and method for non-invasively quantifying the hydration of the stratum corneum of a living subject utilizes in vivo spectral measurements made by irradiating skin tissue with near infrared (NIR) light. The apparatus includes a spectroscopic instrument in conjunction with a subject interface. The resulting NIR absorption spectra are passed to an analyzer for further processing, which includes detecting and eliminating invalid spectral measurements, and preprocessing to increase the signal-to-noise ratio. Finally, a calibration model developed from an exemplary set of measurements is applied to predict the SC hydration for the sample. The method of SC hydration measurement provides additional information about primary sources of systematic tissue variability, namely, the water content of the epidermal layer of skin and the penetration depth of the incident light.

Abstract: A fiber optic probe placement guide minimizes sampling errors during optical sampling of a tissue measurement site by allowing repeatable placement of the fiber optic probe at a targeted tissue measurement site. A mount, contoured to conform to the shape of the tissue measurement site, typically the arm of a human subject, contains an aperture for receiving a fiber optic probe. A temperature probe on the contact surface of the guide allows for monitoring of surface temperature within the vicinity of the tissue measurement site. Crosshair slots in the mount align with corresponding crosshairs at the tissue measurement site. The fiber optic probe placement guide is affixed to the tissue measurement site by means of adhesive tape or fastenable straps. Guideposts on the external surface of the mount are received by corresponding receptacles on a subject interface bearing the fiber optic probe to facilitate alignment of the fiber optic probe with the aperture.

Abstract: The invention provides a design process that is used in the determination of the pattern of detector and illumination optical fibers at the sampling area of a subject. Information about the system, specifically a monochromator (e.g. to determine the optimal number of fibers at an output slit) and the bundle termination at a detector optics stack (e.g. to determine the optimal number of fibers at the bundle termination), is of critical importance to this design. It is those numbers that determine the ratio and number of illumination to detection fibers, significantly limiting and constraining the solution space. Additional information about the estimated signal and noise in the skin is necessary to maximize the signal-to-noise ratio in the wavelength range of interest. Constraining the fibers to a hexagonal perimeter and prescribing a hex-packed pattern, such that alternating columns contain illumination and detection fibers, yields optimal results.

Abstract: An in vivo, non-invasive method of tissue classification using near-IR (NIR) spectral measurements. A classification model is based on NIR spectral absorbance measurements from an exemplary population. Spectral features representing variation between tissue types are identified. Analytic techniques enhance the features of interest and correct spectral interference to improve the predictive ability of the classification model. A classification routine defines classes based on variation between tissue types, such that variation within a class is small compared to variation between classes. A decision rule assigns individual samples from the exemplary population to classes. An in-vivo, non-invasive procedure applies the classification model to individual tissue samples. A preferred embodiment of the invention distinguishes transgenic mice from non-transgenic individuals based on variation in fat composition within muscle tissue.

Abstract: An intelligent system for measuring blood analytes noninvasively operates on a near infrared absorbance spectrum of in vivo skin tissue. An hierarchical architecture employs a pattern classification engine to adapt the calibration to the structural properties and physiological state of the subject as manifested in the absorbance spectrum. A priori information about the primary sources of sample variability are used to establish general categories of subjects. By applying calibration schemes specific to the various categories, the spectral interference is reduced resulting in improved prediction accuracy and parsimonious calibrations. Two classification rules are disclosed. The first rule assumes the classes are mutually exclusive and applies specific calibration models to the various subject categories. The second rule uses fuzzy set theory to develop calibration models and blood analyte predictions.

Abstract: A method is described for determining the concentration of an organic blood analyte using multi-spectral analysis in the near infrared and mid-infrared ranges. Incident radiation containing a plurality of distinct, nonoverlapping regions of wavelengths in the range of approximately 1100 to 5000 nm is used to scan a sample. Diffusively reflected radiation emerging from the sample is detected, and a value indicative of the concentration of the analyte is obtained using an application of chemometrics techniques. Information obtained from each nonoverlapping region of wavelengths can be cross-correlated in order to remove background interferences.

Abstract: One or more basis sets are applied to a spectroscopic signal during analysis to produce an accurate spectral representation from which analyte concentration may be accurately determined. A basis set includes all interfering components found in a sample, such as serum. With regard to an analyte, such as glucose, it is necessary to define those components of a sample that have a larger interference than that of glucose. A basis set may be generated, for example, that produces a transform for the red blood cells that interfere or scatter the light; and also for skin effects. Once the spectra of all these components is known, it is then necessary to determine how each of these components interact, e.g. taking serum data, extracting each of the components, and then comparing the spectra for the individual components with that of the components in solution.

Abstract: A method and apparatus are described for determining the concentration of an organic blood analyte using multi-spectral analysis in the near infrared and mid-infrared ranges. Incident radiation containing a plurality of distinct, nonoverlapping regions of wavelengths in the range of approximately 1100 to 5000 nm is used to scan a sample. Diffusively reflected radiation emerging from the sample is detected, and a value indicative of the concentration of the analyte is obtained using an application of chemometrics techniques. Information obtained from each nonoverlapping region of wavelengths can be cross-correlated in order to remove background interferences.

Abstract: An apparatus is provided for determining the concentration of an analyte present in a sample using multi-spectral analysis in the near-infrared (NIR) range. Incident radiation containing a plurality of distinct, nonoverlapping spectral regions of wavelengths in the near-infrared range is used to irradiate the sample. Diffusively reflected radiation emerging from the sample is detected, and a value indicative of the concentration of the analyte is obtained therefrom, preferably using an application of chemometrics techniques. Information obtained from each of the nonoverlapping spectral regions of wavelengths can be cross-correlated to remove background interference.

Abstract: A number of optically active elements are provided that enable the performance of accurate, dependable chemical analysis in a medium having varying matrix backgrounds and substantial component interferences. Optical transfer cells are provided that include positive correlation filter systems adapted to accept near-IR radiation and to pass a wavelength from that radiation having high correlation with a particular analyte. A near-IR spectrometer apparatus for the measurement of analyte concentration in a complex medium is also provided. The apparatus features an optical transfer cell constructed according to the invention. The apparatus can be used in the non-invasive determination of blood analyte concentrations in a variety of mediums. Methods of measuring the concentration of a blood analyte in a mammalian subject are also provided. The methods entail the use of reflective near-IR radiation to interrogate a medium to obtain spectrally modified radiation.

Abstract: The concentration of an analyte present in a sample is determined using multi-spectral analysis in the near infrared range. Incident radiation containing a plurality of distinct, nonoverlapping regions of wavelengths in the range of approximately 1100 to 3500 nm is used to scan the sample. Diffusively reflected radiation emerging from the sample is detected, and a value indicative of the concentration of the analyte is obtained using an application of chemometrics techniques. Information obtained from each nonoverlapping region of wavelengths can be cross-correlated to remove background interferences.