Radiant energy – Invisible radiant energy responsive electric signalling – Infrared responsive
Reexamination Certificate
1999-07-01
2002-09-03
Hannaher, Constantine (Department: 2878)
Radiant energy
Invisible radiant energy responsive electric signalling
Infrared responsive
Reexamination Certificate
active
06444985
ABSTRACT:
TECHNICAL FIELD OF THE INVENTION
Isotopic analyses are useful for diagnosis of a disease in a medical application, in which metabolic functions of a living body can be determined by measuring a change in the concentration or concentration ratio of an isotope after administration of a drug containing the isotope. In the other fields, the isotopic analyses are used for studies on the photosynthesis and metabolism of plants, and for ecological tracing in a geochemical application.
The present invention relates to stable isotope measurement methods and apparatus for spectrometrically measuring the concentration or concentration ratio of an isotopic gas on the basis of the light absorption characteristics of the isotope.
BACKGROUND ART
It is generally known that gastric ulcer and gastritis are caused by bacteria called helicobacter pylori (HP) as well as by a stress.
If the HP is present in the stomach of a patient, an antibiotic or the like should be administered to the patient for bacteria removal treatment. Therefore, it is indispensable to check if the patient has the HP. The HP has a strong urease activity for decomposing urea into carbon dioxide and ammonia.
Carbon has isotopes having mass numbers of
12
,
13
and
14
, among which
13
C having a mass number of
13
is easy to handle because of its non-radioactivity and stability.
If the concentration of
13
CO
2
as a final metabolic product or the concentration ratio of
13
CO
2
to
12
CO
2
in breath of a patient is successfully measured after urea labeled with the isotope
13
C is administered to the patient, the presence of the HP can be confirmed.
However, the concentration ratio of
13
CO
2
to
12
CO
2
in naturally occurring carbon dioxide is 1:100. Therefore, it is difficult to determine the concentration ratio in the breath of the patient with high accuracy.
There have been known methods for determining the concentration ratio of
13
CO
2
to
12
CO
2
by way of infrared spectroscopy (see Japanese Examined Patent Publications No. 61-42219 (1986) and No. 61-42220 (1986)).
In the method disclosed in Japanese Examined Patent Publication No. 61-42220, two cells respectively having a long path and a short path are provided, the path lengths of which are adjusted such that the light absorption by
13
CO
2
in one cell is equal to the light absorption by
12
CO
2
in the other cell. Light beams transmitted through the two cells are led to the detectors, in which the light intensities are measured at wavelengths which ensure the maximum sensitivity. In accordance with this method, the light absorption ratio for the concentration ratio of
13
CO
2
to
12
CO
2
in naturally occurring carbon dioxide can be adjusted to 1. If the concentration ratio is changed, the light absorption ratio also changes by the amount of a change in the concentration ratio. Thus, the change in the concentration ratio can be determined by measuring the change in the light absorption ratio.
DISCLOSURE OF THE INVENTION
A. However, the method for determining the concentration ratio according to the aforesaid literature suffers from the following drawback.
Calibration curves for determining the concentrations of
12
CO
2
and
13
CO
2
should be prepared by using gas samples each having a known
12
CO
2
concentration and gas samples each having a known
13
CO
2
concentration.
To prepare the calibration curve for the
12
CO
2
concentration, the
12
CO
2
absorbances are measured for different
12
CO
2
concentrations. The
12
CO
2
concentrations and the
12
CO
2
absorbances are plotted as abscissa and ordinate, respectively, and the calibration curve is determined by the method of least squares.
The calibration curve for the
13
CO
2
concentration is prepared in the same manner as described above.
The
13
CO
2
concentration or the
13
CO
2
concentration ratio (which is herein meant by
13
CO
2
concentration/
12
CO
2
concentration) in the breath as a test gas sample is typically determined by way of infrared spectroscopy. In this case, since a test sample gas, or breath is exhaled from a living body as a result of the metabolism, the breath contains water vapor in a concentration proximate to saturation.
In the infrared spectroscopy, the absorption of infrared radiation with a particular wavelength by a test gas sample is utilized for determination of the absorbance for the test gas sample.
FIG. 5
is a graph obtained by plotting the measured values of the
13
CO
2
concentration ratio changes with respect to the humidities of test gas samples having different humidities ranging from 0 to 100% wherein the
13
CO
2
concentration ratio with respect to a 0%-humidity gas sample is used as a reference gas sample.
As can be seen from the graph, the measured values of the
13
CO
2
concentration ratio are not the same, but vary depending on the humidity.
Therefore, if the
13
CO
2
concentration or the
13
CO
2
concentration ratio of a test gas sample containing moisture is measured in ignorance of this fact, the measured value is apparently greater than the true value.
One approach to this problem is to remove the moisture contained in the breath sample as the test gas sample through molecular sieving or with the use of a moisture absorbent such as magnesium perchlorate prior to the measurement. However, some problems may be encountered in this approach since the approach requires a large space for housing the moisture absorbent, there is no means for checking if the moisture is completely removed by the moisture absorbent, and the moisture absorbent should periodically be replaced with a new one.
It is, therefore, an object of the present invention to provide a stable isotope measurement method and apparatus for spectrometrically analyzing an isotopic gas, wherein a test gas sample containing carbon dioxide
13
CO
2
as a component gas is introduced into a cell and the concentration or concentration ratio of the component gas is precisely measured and corrected by measuring moisture content in the test gas sample.
A stable isotope measurement method for spectrometrically analyzing an isotopic gas in accordance with the present invention comprises: a first step of introducing a test gas sample into a cell and determining the absorbance of light transmitted therethrough at a wavelength suitable for the component gas
13
CO
2
; a second step of determining a concentration of the component gas in the test gas sample on the basis of a calibration curve prepared through measurement on test gas samples each containing the component gas in a known concentration; and a third step of measuring a concentration of water vapor contained in the test gas sample and correcting a concentration of the component gas contained in the test gas sample in accordance with the measured water vapor concentration on the basis of a correction curve prepared through measurement on test gas samples each containing water vapor in a known concentration.
A stable isotope measurement method for spectrometrically analyzing an isotopic gas in accordance with the present invention comprises: a first step of introducing a test gas sample containing carbon dioxide
13
CO
2
and carbon dioxide
13
CO
2
as component gases into a cell and determining the absorbances of light transmitted therethrough at wavelengths suitable for the respective component gases; a second step of determining a concentration ratio between the component gases in the test gas sample on the basis of a calibration curve prepared through measurement on test gas samples each containing the component gases in known concentrations; and a third step of measuring a concentration of water vapor contained in the test gas sample and correcting a concentration ratio between the component gases contained in the test gas sample in accordance with the measured water vapor concentration on the basis of a correction curve prepared through measurement on test gas samples each containing water vapor in a known concentration.
When compared with the prior art method, each of the aforesaid methods additionally include the third st
Kubo Yasuhiro
Mori Masaaki
Tsutsui Kazunori
Finnegan Henderson Farabow Garrett & Dunner LLP
Hannaher Constantine
Otsuka Pharmaceutical Co. Ltd.
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