Abstract: A method and apparatus for calibrating noninvasive or implantable glucose analyzers that uses either alternative invasive glucose determinations or noninvasive glucose determinations to calibrate noninvasive or implantable glucose analyzers. Use of an alternative invasive or noninvasive glucose determination in the calibration allows minimization of errors due to sampling methodology, and spatial and temporal variations that are built into the calibration model. An additional embodiment uses statistical correlations between noninvasive and alternative invasive glucose determinations and traditional invasive glucose determinations to adjust noninvasive or alternative invasive glucose concentrations to traditional invasive glucose concentrations. The invention provides a means for calibrating on the basis of glucose determinations that reflect the matrix observed and the variable measured by the analyzer more closely.

Abstract: The invention involves the monitoring of a biological parameter through a compact analyzer. The preferred apparatus is a spectrometer based system that is attached continuously or semi-continuously to a human subject and collects spectral measurements that are used to determine a biological parameter in the sampled tissue. The preferred target analyze is glucose. The preferred analyzer is a near-IR based glucose analyzer for determining the glucose concentration in the body.

Abstract: Methods and system for noninvasive determination of tissue analytes utilize tissue properties as reflected in key features of an analytical signal to improve measurement accuracy and precision. Physiological conditions such as changes in water distribution among tissue compartments lead to complex alterations in the measured analytical signal of skin, leading to a biased noninvasive analyte measurement. Changes in the tissue properties are detected by identifying key features in the analytical signal responsive to physiological variations. Conditions not conducive to the noninvasive measurement are detected. Noninvasive measurements that are biased by physiological changes in tissue are compensated. In an alternate embodiment, the analyte is measured indirectly based on natural physiological response of tissue to changes in analyte concentration. A system capable of such measurements is provided.

Abstract: Methods for calibrating noninvasive or implantable glucose analyzers utilize either alternative invasive glucose determinations or noninvasive glucose determinations for calibrating noninvasive or implantable glucose analyzers. Use of an alternative invasive or noninvasive glucose determination in the calibration allows minimization of errors due to sampling methodology, and spatial and temporal variation that are built into the calibration model. An additional method uses statistical correlations between noninvasive and alternative invasive glucose determinations and traditional invasive glucose determinations to adjust noninvasive or alternative invasive glucose concentrations to traditional invasive glucose concentrations. The methods provide a means for calibrating on the basis of glucose determinations that reflect the matrix observed and the variable measured by the analyzer more closely.

Abstract: Methods and apparatus for noninvasive determination of blood analytes, such as glucose, through NIR spectroscopy utilize optical properties of tissue as reflected in key spectroscopic features to improve measurement accuracy and precision. Physiological conditions such as changes in water distribution among tissue compartments lead to complex alterations in the measured absorbance spectrum of skin and reflect a modification in the effective pathlength of light, leading to a biased noninvasive glucose measurement. Changes in the optical properties of tissue are detected by identifying key features responsive to physiological variations. Conditions not conducive to noninvasive measurement of glucose are detected. Noninvasive glucose measurements that are biased by physiological changes in tissue are compensated. In an alternate embodiment, glucose is measured indirectly based on natural physiological response of tissue to glucose concentration. A spectroscopic device capable of such measurements is provided.

Abstract: A ceramic reference in conjunction with a spectrometer, a metallized ceramic material, and a method of utilizing a ceramic material as a reference in the ultraviolet, visible, near-infrared, or infrared spectral regions are presented. The preferred embodiments utilize a ceramic reference material to diffusely reflect incident source light toward a detector element for quantification in a reproducible fashion. Alternative embodiments metallize either the incident surface or back surface of to form a surface diffuse reflectance standard. Optional wavelength reference layers or protective layers may be added to the ceramic or to the metallized layer. The reference ceramic is used to provide a measure of optical signal of an analyzer as a function of the analyzers spatial, temporal, and environmental state.

Abstract: A placement guide apparatus with an improved hydration inducing plug used in coupling a noninvasive analyzer to a sampling site to determine analyte in the human body is disclosed. The hydration inducing plug includes at least one fluoropolymer that may be used as a coupling agent. The guide apparatus may further include an automated or semi-automated coupling fluid delivery system. Use of either of these couplers mitigates issues associated with related technology and enhances noninvasive analyte measurements, such as a near-IR diffuse reflectance based noninvasive glucose concentration analyzer.

Abstract: The invention provides a method of determining an individual's glucose metabolism sensitivity based upon the shape of a glucose profile in response to a stimulus, such as a caloric challenge. The sensitivity of an individual may be used to project a glucose response profile or to achieve a targeted response in the individual's blood glucose concentrations in response to a stimulus, such as medication, exercise, or caloric intake. An actual glucose response to a stimulus is determined using parameters that measure the shape of a glucose profile resulting from the stimulus. The glucose response provides rapid feedback of an individual's diabetic state.

Abstract: A ceramic reference in conjunction with a spectrometer, a metallized ceramic material, and a method of utilizing a ceramic material as a reference in the ultraviolet, visible, near-infrared, or infrared spectral regions are presented. The preferred embodiments utilize a ceramic reference material to diffusely reflect incident source light toward a detector element for quantification in a reproducible fashion. Alternative embodiments metallize either the incident surface or back surface of to form a surface diffuse reflectance standard. Optional wavelength reference layers or protective layers may be added to the ceramic or to the metallized layer. The reference ceramic is used to provide a measure of optical signal of an analyzer as a function of the analyzers spatial, temporal, and environmental state.

Abstract: A method of screening for disorders of glucose metabolism such as impaired glucose tolerance and diabetes allows prevention, or early detection and treatment of diabetic complications such as cardiovascular disease, retinopathy, and other disorders of the major organs and systems. A mathematical algorithm evaluates the shape of a subject's glucose profile and classifies the profile into one of several predefined clusters, each cluster corresponding either to a normal condition or one of several abnormal conditions. The series of blood glucose values making up the glucose tolerance curve may be measured using any glucose analyzer including: invasive, minimally invasive and noninvasive types. The method is executed on a processing device programmed to perform the steps of the method. Depending on the outcome of the screening, a subject may be provided with additional information concerning their condition and/or counseled to consult further with their health care provider.

Abstract: A method of screening for disorders of glucose metabolism such as impaired glucose tolerance and diabetes allows prevention, or early detection and treatment of diabetic complications such as cardiovascular disease, retinopathy, and other disorders of the major organs and systems. A mathematical algorithm evaluates the shape of a subject's glucose profile and classifies the profile into one of several predefined clusters, each cluster corresponding either to a normal condition or one of several abnormal conditions. The series of blood glucose values making up the glucose tolerance curve may be measured using any glucose analyzer including: invasive, minimally invasive and noninvasive types. The method is executed on a processing device programmed to perform the steps of the method. Depending on the outcome of the screening, a subject may be provided with additional information concerning their condition and/or counseled to consult further with their health care provider.

Abstract: Methods and system for noninvasive determination of tissue analytes utilize tissue properties as reflected in key features of an analytical signal to improve measurement accuracy and precision. Physiological conditions such as changes in water distribution among tissue compartments lead to complex alterations in the measured analytical signal of skin, leading to a biased noninvasive analyte measurement. Changes in the tissue properties are detected by identifying key features in the analytical signal responsive to physiological variations. Conditions not conducive to the noninvasive measurement are detected. Noninvasive measurements that are biased by physiological changes in tissue are compensated. In an alternate embodiment, the analyte is measured indirectly based on natural physiological response of tissue to changes in analyte concentration. A system capable of such measurements is provided.

Abstract: Methods and apparatus for noninvasive determination of blood analytes, such as glucose, through NIR spectroscopy utilize optical properties of tissue as reflected in key spectroscopic features to improve measurement accuracy and precision. Physiological conditions such as changes in water distribution among tissue compartments lead to complex alterations in the measured absorbance spectrum of skin and reflect a modification in the effective pathlength of light, leading to a biased noninvasive glucose measurement. Changes in the optical properties of tissue are detected by identifying key features responsive to physiological variations. Conditions not conducive to noninvasive measurement of glucose are detected. Noninvasive glucose measurements that are biased by physiological changes in tissue are compensated. In an alternate embodiment, glucose is measured indirectly based on natural physiological response of tissue to glucose concentration. A spectroscopic device capable of such measurements is provided.

Abstract: A method and apparatus for noninvasive glucose measurement measures glucose indirectly from the natural response of tissue to variations in analyte concentration. The indirect measurement method utilizes factors affected by or correlated with the concentration of glucose, such as refractive index, electrolyte distribution or tissue scattering. Measurement reliability is greatly improved by stabilizing optical properties of the tissue at the measurement site, thus blood perfusion rates at the sample site are regulated. Perfusion is monitored and stabilized by spectroscopically measuring a control parameter, such as skin temperature, that directly affects perfusion. The control parameter is maintained in a range about a set point, thus stabilizing perfusion. Skin temperature is controlled using a variety of means, including the use of active heating and cooling elements, passive devices, such as thermal wraps, and through the use of a heated coupling medium having favorable heat transfer properties.

Abstract: Methods for calibrating noninvasive or implantable glucose analyzers utilize either alternative invasive glucose determinations or noninvasive glucose determinations for calibrating noninvasive or implantable glucose analyzers. Use of an alternative invasive or noninvasive glucose determination in the calibration allows minimization of errors due to sampling methodology, and spatial and temporal variation that are built into the calibration model. An additional method uses statistical correlations between noninvasive and alternative invasive glucose determinations and traditional invasive glucose determinations to adjust noninvasive or alternative invasive glucose concentrations to traditional invasive glucose concentrations. The methods provide a means for calibrating on the basis of glucose determinations that reflect the matrix observed and the variable measured by the analyzer more closely.

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: An optical sampling interface system minimizes and compensates error resulting from sampling variations and measurement site state fluctuations. Components include: An optical probe placement guide having an aperture wherein the optical probe is received, facilitates repeatable placement accuracy on surface of a tissue measurement site with minimal, repeatable disturbance to surface tissue. The aperture creates a tissue meniscus that minimizes interference due to surface irregularities and controls variation in tissue volume sampled; an occlusive element placed over the tissue meniscus isolates the meniscus from environmental fluctuations, stabilizing hydration at the site and thus, surface tension; an optical coupling medium eliminates air gaps between skin surface and optical probe; a bias correction element applies a bias correction to spectral measurements, and associated analyte measurements. When the guide is replaced, a new bias correction is determined for measurements done with the new placement.

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.