Instrumentation Metrics, Inc.

Sensys Medical, Inc.

Stephen F Malin

Timothy Lewis Ruchti

Suresh Thennadil

Gamal Khalil

Kevin H Hazen

Jessica Rennert

Thomas B Blank

Alexander D Lorenz

Tamara L Troy

James Matthew Welch

Glenn Aaron Kees

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;' and &mgr; . 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. In particular, knowledge may be gained on net analyte signal, photon depth of penetration, photon radial diffusion, photon interaction between tissue layers, photon density (all as a function of frequency) and on instrument parameter specifications such as resolution and required dynamic range (A/D bits required). In particular, applications to delineate such parameters have been developed for the application of noninvasive glucose determination in the near-IR region from 700 to 2500 nm with an emphasis on the region 1000 to 2500 nm (10,000 to 4,000 cm ).

Intra-serum and intra-gel for modeling human skin tissue

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.

System for the noninvasive estimation of relative age

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.

Classification system for sex determination and tissue characterization

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;m and &mgr;m . 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. In particular, knowledge may be gained on net analyte signal, photon depth of penetration, photon radial diffusion, photon interaction between tissue layers, photon density (all as a function of frequency) and on instrument parameter specifications such as resolution and required dynamic range (A/D bits required). In particular, applications to delineate such parameters have been developed for the application of noninvasive glucose determination in the near-IR region from 700 to 2500 nm with an emphasis on the region 1000 to 2500 nm (10,000 to 4,000 cm&minus; ).

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.

Non-invasive in vivo tissue classification using near-infrared measurements

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. Therefore, each calibration sample has the opportunity to influence more than one calibration model according to its class membership. Similarly, the predictions from more than one calibration are combined through defuzzification to produce the final blood analyte prediction.

Intelligent system for noninvasive blood analyte prediction

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.

Method for multi-spectral analysis of organic blood analytes in noninvasive infrared spectroscopy

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. The invention characterizes each component in a sample, as well as all other possible interferants and, after producing an accurate representation of each component at each frequency of interest, identifies and subtracts each interferant from the spectra produced at the frequency of interest. The basis sets may take the form of transforms that may be stored in a look-up table for use during analysis.

Method and apparatus for generating basis sets for use in spectroscopic

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.

Method and apparatus for multi-spectral analysis of organic blood

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.

Method and apparatus for multi-spectral analysis in noninvasive NIR

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.

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Glendale, CA, United States of America

Stephen F Malin