Method and apparatus for molecular spectroscopy, particularly fo

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128633, G01J 100

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044278896

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BRIEF SUMMARY
The present invention relates to a method of molecular spectroscopy, particularly for the determination of products of metabolism, in which the absorption of infrared radiation by a specimen containing a substance to be determined is measured, as well as to an apparatus for the carrying out of this method.
The method and the apparatus of the invention can be used in particular for the determination of glucose in serum or in urine. Such a determination is of great importance for the recognition of diabetes mellitus and as check-up on the treatment thereof. The known determination by means of test strips in urine serves primarily to detect the disease. Although a well-stabilized diabetic can, in case of regular examination of the urine, get along with a few spot checks of blood glucose, the determination of the concentration of glucose in the blood is essentially of importance for treatment, verification of treatment and adjustment of the daily profile.
The known methods for the determination of glucose can be divided into three groups, namely biochemical, electrochemical and spectroscopic methods. Of these methods, the biochemical methods are suitable only as laboratory procedures; the electrochemical methods, to be sure, at present afford the most promising prospects for the development of implantable glucose sensors but are inferior in their precision and specificity to the spectroscopic methods, as the biochemical methods also are.
The biochemical and electrochemical methods furthermore have the common disadvantage that the specimen to be measured must be so prepared by addition of chemicals before the actual measurement process as to form reaction products which can be detected in the measurement. Thus continuous measurements are not possible.
In contradistinction to the biochemical and electrochemical methods, the glucose molecule is not modified in the spectroscopic method.
In addition, there are still a few non-specific methods which are practically no longer used. Thus, for instance, from German Pat. No. 2 724 543 a method is known for determining glucose based on the long-known polarimetry, which, however, is today rarely used because of insufficient specificity, it being suitable at most under favorable conditions for the determination of sugar in the urine.
A first possibility of determining products of metabolism by spectroscopic measurement is represented by laser Raman spectroscopy. The frequency of the exciter radiation is here in the visible spectral range. For the measurement, the portion in the spectrum of the scattered light which is shifted towards the red is used.
In measurements in whole blood the difficulty is encountered in this method of measurement that, due to the hemoglobin and the other chromophoric substances, blood exhibits strong absorption throughout the entire visible spectral range, which, to be sure, leads to a reinforcement of the resonance of the Raman scattering for these molecules but has a high fluorescence background associated with it and thus makes the detection of non resonance-reinforced bands difficult if not entirely impossible. This problem, to be sure, can be solved with the presently available possibilities of exciting the Raman scattering with short laser pulses in the subnanosecond range; however, the technical expenditure is so substantial that it will not be possible in the foreseeable future to find any practical method with it for samples of whole blood.
Another possibility of avoiding the disturbance by fluorescence of the chromophores consists in operating in the infrared spectral range, i.e. in recording directly the infrared spectrum of the specimen. However, since the preparation of the specimen as well as the recording and evaluation of the spectrum are time-consuming and complicated, infrared spectroscopy of the type customary up to now does not constitute competition for the other methods which exist.
Another spectroscopic method is the so-called attenuated total reflectance (ATR) spectroscopy, i.e. total reflectance spectroscopy with transver

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patent: 3958560 (1976-05-01), March
patent: 4044257 (1977-08-01), Kreuzer
patent: 4100416 (1978-07-01), Hirschfeld
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