Abstract: A method for classifying live subjects according to optical thickness of the skin is based on noninvasive, near-infrared reflectance measurements on skin tissue. An indicator of skin optical thickness is derived through analysis of the water, fat, and protein marker bands in the near infrared spectrum. The skin thickness indicator may then be used to evaluate the suitability of the subject for calibration on a standardized set of optical probes. The optical probes in the standardized set are designed to cover a range of penetration depths by varying the distance distribution between illuminator and detector fibers on each probe tip.

Abstract: Methods and apparatus for estimating and removing spectral interference improve precision and robustness of non-invasive analyte measurement using Near-infrared (NIR) spectroscopy. The estimation of spectral interference is accomplished, either through multivariate modeling or discrete factor analysis, using a calibration set of samples in which the interference is orthogonal to the analyte signal of interest, or where the shape of the interference is known. Each of the methods results in a multivariate model in which the spectral interference is estimated for a new sample and removed by vector subtraction. Independent models based on classes of sample variability are used to collapse spectral interference and determine more accurately which model is best equipped to estimate the signal of interference in the new sample. Principal components analysis and other commonly known analytical techniques can be used to determine class membership.

Abstract: An apparatus and method for non-destructively estimating a tissue property, such as hydration, 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 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, an estimation model developed from an exemplary set of measurements is applied to predict the tissue hydration for the sample. The method of tissue 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: 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 method and apparatus for minimizing confounding effects in a noninvasive in-vivo spectral measurement caused by fluctuations in tissue state monitors a selected tissue state parameter spectroscopically and maintains the selected parameter within a target range, at which spectral effects attributable to the changes in the selected parameter are minimized. The invention includes both active and passive control. A preferred embodiment of the invention provides a method and apparatus for minimizing the confounding effects in near IR spectral measurements attributable to shifts in skin temperature at a tissue measurement site. Spectroscopic monitoring of skin temperature at the measurement site provides near-instantaneous temperature readings by eliminating thermal time constants. A thermistor positioned at the measurement site provides active control. The spectrometer and the temperature control device are incorporated into a single instrument for noninvasive measurement of blood glucose concentration.

Abstract: The invention provides a mechanism for oscillating the spectral grating of a monochromator. The mechanism couples the spectral grating of the monochromator to an oscillating spatial linkage mechanism which accepts a rotational input and converts it into an oscillatory motion. A monochromator according to the invention comprises an oscillating grating that is oscillated by such spacial linkage mechanism drive.

Abstract: An embedded data acquisition and control system for a precision instruments, such as a non-invasive glucose prediction instrument is disclosed. One feature of the invention provides synchronization of stepper motor position and analog-to-digital converters. An embedded controller is provided that controls the stepper motor driver directly to minimize the wavelength shift error due to the asynchronous condition. The controller synchronizes the event of reading the A/D converters with each stepper motor position. Because the stepper motor controls the wavelength of the monochromator optical output, the net result is that each A/D conversion recorded by the embedded controller is precisely tracked to a specific wavelength. Another feature of the invention provides closed loop motor position control for enhanced system performance. In the closed loop system, a position encoder is coupled to the stepper motor shaft.

Abstract: An apparatus for varying localized absorption and scattering coefficients at a tissue measurement site in a controlled and reproducible manner during optical sampling of a tissue volume by controlling the pressure applied to a tissue measurement site by a spectroscopic analyzer allows applied pressure to be maintained at a constant level, or the applied pressure may be varied in a controlled, reproducible manner as a function of time. A rest for receiving a body part holds the body part in a fixed position and at a fixed elevation. A mechanical system advances a fiber optic probe until it makes contact with the body part with a constant amount of pressure. The applied force is supplied by a counterweight on a single arm balance. A temperature control allows the temperature of the fiber optic probe to be equilibrated with the temperature in the immediate vicinity of the tissue measurement site.

Abstract: A method of multi-tier classification and calibration in noninvasive blood analyte prediction minimizes prediction error by limiting co-varying spectral interferents. Tissue samples are categorized based on subject demographic and instrumental skin measurements, including in vivo near-IR spectral measurements. A multi-tier intelligent pattern classification sequence organizes spectral data into clusters having a high degree of internal consistency in tissue properties. In each tier, categories are successively refined using subject demographics, spectral measurement information and other device measurements suitable for developing tissue classifications. The multi-tier classification approach to calibration utilizes multivariate statistical arguments and multi-tiered classification using spectral features.

Abstract: A method of multi-tier classification and calibration in noninvasive blood analyte prediction minimizes prediction error by limiting co-varying spectral interferents. Tissue samples are categorized based on subject demographic and instrumental skin measurements, including in vivo near-IR spectral measurements. A multi-tier intelligent pattern classification sequence organizes spectral data into clusters having a high degree of internal consistency in tissue properties. In each tier, categories are successively refined using subject demographics, spectral measurement information and other device measurements suitable for developing tissue classifications. The multi-tier classification approach to calibration utilizes multivariate statistical arguments and multi-tiered classification using spectral features.

Abstract: Noninvasive instrumentation and procedures have been developed for estimating the apparent age of human and animal subjects based on the irradiation of skin tissue with near-infrared light. The method of age estimation provides additional information about primary sources of systematic tissue variability due to chronological factors and environmental exposure. Therefore, categorization of subjects on the basis of the estimated apparent age is suitable for further spectral analysis and the measurement of biological and chemical compounds, such as blood analytes. Furthermore, age determination of subjects has particular benefit in assessment of therapies used to reduce the effects of ageing in tissue and measurement of tissue damage.

Abstract: A method of calibrating a non-invasive blood glucose measurement instrument to a diabetic test subject employs targeted glycemic profiles in anti-correlated pairs. During calibration, reference blood glucose determinations are made using conventional invasive sampling methods. Concurrently, noninvasive spectral measurements are made using the noninvasive glucose monitor. Through controlled oral ingestion by the subject of calculated amounts of carbohydrate, the subject's blood glucose level is manipulated to mimic the patterns of the targeted profiles. During a first visit, a first profile of a pair is induced; during a second visit the inverse of the first profile is induced. The targeted profiles produce reference blood glucose values in which correlation to sampling factors is reduced or eliminated, thus the resulting calibration is correlated to glucose, and not to other analytes, sampling factors or environmental factors.

Abstract: A novel approach to measuring the overall and layer-by-layer thickness of in vivo skin tissue based on near infrared absorbance spectra is described. The different biological and chemical compounds present in the various layers of a tissue sample have differing absorbance spectra and scattering properties that enable them to be discerned and quantified, thus allowing an estimate of the thickness of the tissue being sampled. The method of the invention also yields the chemical composition of the absorbing and/or scattering species of each layer. Additionally, a method of path length normalization for the purpose of noninvasive analyte prediction on the basis of skin thickness and layer constituents is provided.