Optics: measuring and testing – For light transmission or absorption – Of fluent material
Reexamination Certificate
2000-09-05
2003-07-15
Rosenberger, Richard A. (Department: 2877)
Optics: measuring and testing
For light transmission or absorption
Of fluent material
C600S532000, C073S023300
Reexamination Certificate
active
06594016
ABSTRACT:
The present invention relates to a method of measuring the effect of a compound on a mammal by measuring the concentration of an organic compound spectroscopically.
Methods of spectroscopically determining the effect of a compound are generally known. As a general example, it is known to administer a compound to a mammal and measure, for example using an ELISA, a second compound as a measure of the physiological effect of the first compound on the mammal.
The object of the present invention is to make it possible to perform sensitive measurements. An additional goal is to make it possible to measure continuously so that fluctuations in the concentration occurring within a short period of time, as a result of the effect of the compound on the mammal, can be detected.
To this end the present invention is characterized in that the organic compound is a volatile organic compound, the concentration of which is measured in a gas given off by the mammal using photoacoustic spectroscopy, the volatile organic compound not being the compound or a degradation product thereof.
Photoacoustic spectroscopy is a spectroscopic technique that makes it possible to perform sensitive measurements without a concentration step. It also makes it possible to measure continuously so that fluctuations in the concentration occurring within a short period of time, can be detected, for example in the breath of the mammal.
Both photoacoustic spectroscopy and breath analysis have been known for some time. But even a very recent review article by Kneepkens, C. M. F. et al. (ref. 2) makes no mention of photoacoustic spectroscopy and its possibilities for measuring the effect of a compound. The same applies to EP 0 757 242 which discloses the use of photoacoustic spectroscopy for detecting the metabolization of a labelled compound, the degradation product thereof being measured.
When mention is made in the present application of a compound to be tested for its effect on a mammal, a compound is meant which is not a tracer. In other words, it is not the compound itself nor one of its decomposition products whose concentration is being measured by the method according to the invention. What is being examined is the physiological effect of the compound on the organism including the compound's protective effect against a stress factor.
According to one embodiment, the mammal is subjected to a factor that changes the concentration of the volatile organic compound in the breath.
Thanks to the fact that with the method according to the invention measuring can be performed continuously, the invention makes it possible to expose the mammal, for example a human, to a stimulus and to determine the effect of the concentration of the volatile organic compound to be measured.
According to a preferred embodiment the factor is a stress factor, in particular UV radiation.
Surprisingly it has been shown that UV radiation influences the composition of breath and that this change can be measured. This opens possibilities for testing products for the protection of skin against UV radiation.
According to a very favourable embodiment the compound is one to be tested for the presence of a pharmaceutical characteristic. For instance, it could be possible to quickly and non-invasively examine the restoring capacity for containing the consequences of a myocardial infarct.
According to a favourable embodiment the measured concentration is normalized. Preferably this is done by using at least one parameter selected from the group comprising weight, lung capacity (measure of lung surface area), respiratory volume (l/min), volume of each breath, blood flow rate, the concentration of a further compound selected from the group comprising a marker gas, carbon dioxide, oxygen; and the mammal's percentage of fat.
In this manner diagnosing can be facilitated or made more reliable, based on the detection of one or more further compounds. As marker gas it is possible to use, for example, SF
6
.
The volatile organic compound is preferably a hydrocarbon composition with the general formula C
x
H
y
, x and y being integers, x≦10 en y≧x is.
Such hydrocarbon compounds can be used for numerous diagnoses.
According to a preferred embodiment the hydrocarbon compound is an unsaturated hydrocarbon compound, in particular ethene.
Ethene was shown to be present in the breath of humans, and to be useful, among other things, for examining the effect of UV radiation on humans.
According to a favourable embodiment a housing which is open at one side and provided with an inlet for a carrier gas, is placed against a portion of a mammal's surface, said portion not comprising an open body orifice, the carrier gas is fed through the housing, and the carrier gas containing the gas given off by the mammal is led away via an outlet in the housing and is subsequently measured photoacoustically.
The surface of the mammal may be any surface that cannot be reached via surgery, and in particular one where blood vessels are close to the surface such as, for instance, the inside of the mouth. Particularly suitable is the skin which is easily accessible and of which a large area can be used, if necessary. The advantage of this embodiment is that it avoids problems arising from the high flow rate of breathing air and the variable composition of one breath, resulting from the fact that the lung's inlet opening for oxygen is the same as the outlet opening. In addition, it becomes easier to normalize concentrations, for example, on the basis of the carbon dioxide that is also given off. Moreover, if desired, the concentration of the compound may be brought into a convenient measuring range by adjusting the flow rate of the carrier gas, by treating the respective portion of the body surface with permeabilizing agents, and/or by suitably dimensioning the surface of the housing covered by the open side. optionally an underpressure may be applied, which promotes blood circulation and the release of gas, or an overpressure, which is a simple manner of avoiding pollutants from the surroundings coming into the gas to be analyzed. Also, the mammal's comfort is not lessened, as may be the case when the breathing is measured. This is in particular the case with patients, such as cardiac patients, who are in a precarious, non-stable condition, and who could be harmed by measurements being performed.
REFERENCES:
patent: 5125749 (1992-06-01), Leugers et al.
patent: 5900533 (1999-05-01), Chou
patent: 0557658 (1993-09-01), None
patent: 0757242 (1997-02-01), None
patent: 1509174 (1978-04-01), None
patent: WO81/02632 (1981-09-01), None
Kneepkens, et al., Free Radical Biology & Medicine, vol. 17, No. 2, pp. 127-160 (Jan. 4, 1994).*
Bijnen, F.G.C., et al., “Geometrical Optimization of a Longitudinal Resonant Photoacoustic Cell for Sensitive and Fast Trace Gas Detection,”Rev. Sci. Instrum., vol. 67, No. 8 Aug. 1996).
Phillips, M., “Breath Tests in Medicine,”Scientific American, pp 32-37 (Jul. 1992).
Bijnen, F.G.C., et al., “Intracavity CO Laser Photoacoustic Trace Gas Detection: Cyclic CH4,H20 and CO2Emission by cockroaches and Scarab Beetles”Applied Optics, vol. 35, No. 27, pp. 5357-5368 (Sep. 20, 1996).
Kneepkens, C.M.F., et al., “The Potential of the Hydrocarbon Breath Test as a Measure of Lipid Peroxidation,”Free Radical Biology and Medicine, vol. 17, No. 2, pp. 127-160 (1994).
Harren Franciscus Johannes Maria
Parker David Hubert
Te Lintel Hekkert Sacco
Barth Vincent P.
Rosenberger Richard A.
Stichting voor de Technische Wetenschappen
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