Process and device for determining an analyte contained in a sca

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356345, G01N 2149

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059628529

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BRIEF SUMMARY
The invention relates to a method and an apparatus for analysing a scattering matrix with respect to an analyte contained therein by means of light.
The most important application of the invention is the analytical investigation of biological samples, in particular of the tissue of a living organism. Biological samples are mostly optically heterogeneous, i.e. they contain a large number of scattering centres at which irradiated light is scattered. This applies to human or animal tissue, in particular skin tissue or subcutaneous fatty tissue, but also to fluid biological samples, such as blood for example, in which the blood corpuscles form scattering centres, or else to milk, in which the scattering centres are formed by emulsified fat droplets.
Furthermore the invention is directed towards scattering matrices in general in which an analyte is to be determined qualitatively or quantitatively. A scattering matrix in this sense is a three-dimensional structure with such a high density of optical scattering centres that irradiated light is generally scattered many times before it leaves the scattering matrix again. Non-biological scattering matrices which can be investigated on the basis of the present invention are for example emulsions and dispersions such as are required for various purposes, for example for paints and varnishes.
Reference will be made below, without restriction of the general concept, to the analysis of tissue as an example of biological and other scattering matrices.
The object of the analytical methods towards which the invention is directed is the determination of an analyte in the sense that information on the presence of a particular component contained in the tissue is obtained. The information can relate to the concentration of the analyte (quantitative analysis) or simply to the question whether the analyte is contained (in a concentration above the detection limit of the method) in the sample (qualitative analysis).
Analyses of tissues and other biological samples have to date mainly been carried out invasively, i.e. a sample (mostly a blood sample) is removed from the tissue, and the analyte concentration therein is determined by means of reagents.
There has been increasing discussion in recent times of non-invasive methods of analysis, in which the analytical result is determined painlessly and without reagents from the tissue without sampling. Most of the methods discussed for this purpose are based on the interaction of light with the scattering matrix. In all of these methods, measurement steps are carried out in which light is irradiated into the matrix as primary light through an interface bordering the matrix and light leaving the matrix is detected as secondary light. The purpose of this is to measure a measurable physical property of the light which varies due to the interaction of the light with the matrix and which correlates with the concentration of the analyte in the matrix. Such a procedural step will be described here as the "detection step" and the measurement as the "detection measurement". A detection step may include one or more detection measurements.
The wavelengths of light which are discussed for such methods lie in general between about 300 nanometers (nm) and several thousand nanometers, i.e. in the spectral range between near-UV and infrared light. The physical property of light which can be determined (detected) in the detection step, which can also be described as the "quantifiable parameter", will be described below as the "measurement quantity" for the sake of simplicity.
An absolute measurement of the analyte concentration is generally not possible with the methods discussed here. Therefore a calibration is required (as with most of the analytical methods based on chemical reactions). In at least one calibration step, which is performed with the same measuring techniques as a detection step, at least one detection measurement is carried out on a scattering matrix with a known analyte concentration. In the analysis of living tissue, this takes plac

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patent: 5565986 (1996-10-01), Knuttel
patent: 5579112 (1996-11-01), Sugiyama et al.
Optics Letters, vol. 11, No. 3, Mar., 1986, "Femotosecond Optical Ranging in Biological Systems", Fujimoto et al pp. 150-152.
Applied Optics, vol. 32, No. 26, Sep. 10, 1993, "Time-Resolved Fourier Spectrum and Imaging in Highly Scattering Media", Wang et al pp. 5043-5048.
Biophys. J., Biophysical Society, vol. 44, Dec., 1983, pp. 315-324, "A Continuously Variable Frequency Cross-Correlation Phase Fluorometer With Picosecond Resolution", Gratton et al.
Applied Optics, vol. 32, No. 30, Oct. 20, 1993, "Measurement of Optical Properties of Biological Tissues by Low-Coherence Reflectometry", Schmitt et al pp. 6032-6042.
SPIE-The International Society for Optical Engineering, vol. 1889, 197-211, "Optical Characterization of Dense Tissues Using Low-Coherence Interferometry", Schmitt et al Jan. 1993.

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