JPH0217446A - Process evaluation by isotope enrichment - Google Patents

Abstract

PURPOSE: To make it possible to directly measure substance concentration by holding gas sample at the pressure for making it possible to distinguish the absorption line of tracer species and the absorption line of related isotope species, transmitting monochromatic radiation therethrough, and detecting the spectral beam intensity for the concentrated species. CONSTITUTION: The wavelength of a tunable diode laser 10 is decided by altering an operating temperature. The applied current is varied to adjust the operating conditions corresponding to various isotope or molecules and to operate at high thermal sinking temperature. Laser radiation transmits a chopper 16 and a lens system 18 to a spectral lattice 20, and passed as single optical mode. The mode is regulated to contain the line of the isotope molecule to be. The radiant beam light is passed through a cell 22 filled with sample gas (including tracer species concentrated by the tracer isotope, pressure of 3200Pa). The light passed through the cell 22 is sensed by a detector 28, the detection signal is processed by a signal processor 30, and the result is displayed on a display unit 32. The lens 18 is replaced with a yawing parabolic mirror to make it possible to remove optical noise.

Description

Detailed Description of the Invention (11) Field of Industrial Application The present invention relates to a stable isotope enrichment method for measuring the influence of a certain system or process on a certain substance. The present invention relates to a method for directly measuring the concentration of species using infrared spectroscopy.

(2) Prior art and the problem to be solved by the invention In clinical biomedical tests, or even in engineering or scientific tests, it is necessary to evaluate certain processes occurring within the human body or other systems. Often. One well-known method is enriched with a tracer, usually in the form of an open body.
) This is a method of measuring substances and evaluating the effects of internal processes on the snow.

The use of radioactive isotopes in this test has been reported in many publications, and valuable information has been accumulated. On the other hand, it is well known that radioactivity has an adverse effect on the human body or other subjects exposed to radiation, and there are also problems with contamination of mechanical systems and waste, making this radioactive tracer method undesirable. It is said that Another drawback is the lack of suitable radioisotopes for all test substances.

Stable isotopes have also been used as tracers.

Regarding this type of tracer application, see ``Stable Isotope Tracers in Biosciences and Medicine J, Matwiyoff
et al., 5science *Volume 181, page 1125 (
September 1973] was discussed. This stable isotope has the advantage of being safe as it does not require exposure to radiation. Another advantage is that there is a wide range of isotopic species that can be used as tracers. The abundant species naturally present in any system usually have chemically equivalent minor or trace isotopic species suitable for enrichment studies. Until now, the practical application of this method was limited because there was no good way to measure the concentration of enriched species.

As shown in the above-mentioned paper published in the journal 5ience, mass spectrometry is used for the determination of stable isotopes, especially in the biomedical field. Although this method provides very accurate results for ratio measurements, direct concentration measurements are not possible in many cases. One problem with mass spectrometry is that
- For some substances, such as carbon oxide (CO), ff! gives an excess.

That is, molecules of the same type made up of different isotopes can have the same mass, making mass separation impossible and making it impossible to use highly useful species as tracer substances. In addition, mass spectrometers are very expensive, require skilled operators, and require a large amount of manipulation to prepare sample f+, so it takes time to obtain results. Because isotopic mass spectrometry determines the ratio of species with different masses, there is often some interfering species with the same mass as the species to be measured, which must be removed before measurement. Removal scouting is not always possible. Isotopic mass spectrometry setups are not so versatile that they can be applied to a wide variety of species. Rather, care is taken to manipulate narrow ranges of the mass spectrum in order to improve resolution for approximate masses. Therefore, while mass spectrometry is useful for research purposes, it is economically unsuitable for general purpose clinical equipment meeting the requirements of the medical field. [-Determination and determination of carbon-13 by infrared spectroscopic analysis of carbon oxide” McDow
e11: Analytical Chemises
tr3'* Vol. 42, p. 1192 (1970) K states that mass spectrometry should be avoided for measuring the Co/Co ratio in a sample that appears to be pure CO. The spectroscopic device cannot separate individual isotope lines in this relatively wide band;
Only rough measurements of ratios can be made. This method cannot measure the exact ratio or the absolute concentration (1). Infrared measurements are also used to measure automobile exhaust, but isotope enrichment is not used. J, Hi The paper by 11 et al.
"Temporal Measurement of Vehicle Sulfate and Methane Emissions with Tunable Diode Lasers", SAE
800510 (February 1980), a tunable diode laser is used to scan the absorption lines of molecules in an exhaust gas sample, but isotopic extrusion is not taken into account. Due to the high pressure of the sample, it was not possible to separate the fine structure of the lines corresponding to a single solid isotope line, and only rough measurements were made.

Infrared absorption spectroscopy is known to be useful for measuring naturally occurring isotopic species. In some cases, the property value measured is the spectrum of the isotope, ie the wavelength of several absorption lines. This is what Jensen et al. (La5er
Focus, Ritsuki, 1976] uses a tunable diode laser to identify the isotope spectrum of natural uranium uranium, but does not mention the measurement of isotope concentrations. In other cases, the measurement of isotope concentration is important and 11 specific precision is emphasized.

For example, Labrie et al.
hysics, Volume 24.

681, 1981] used a tunable diode laser and a multi-pass photocell to measure the carbon-14 concentration in order to measure the carbon dating. It takes several hours. The paper concludes that infrared laser spectroscopy can be used to measure other stable or radioactive isotopes in low abundance. Although this method is interesting, the long measurement time does not meet the requirements of clinical trials. “Isotope Analysis by Infrared Laser Absorption Spectroscopy J, Lehmann et al., Ap
pliedI'hystcs Volume 13, Page 156 (
(1977) discusses a tunable PbS laser for testing isotopically enriched carbon dioxide, confirming the presence of absorption lines for each isotope and measuring absorption coefficients at different pressures. The necessity of a split-beam two-pass system has been shown to obtain accurate results.

Regarding the application of infrared method for stable isotope detection in the biomedical field, see the above-mentioned paper.
1973 in 5science magazine by f f et al.
Infrared devices are not specified there, although they are briefly addressed in a paper published in 2013.

They discuss a method in which a substrate labeled with 13C is ingested, blown into an evacuated bulb, and excess C in exhaled breath is quantified using infrared spectroscopy. However, the difficulty of sample preparation and the accuracy of this method have not been clarified. It is well known that the relatively broad bands in spectroscopic instruments of this age are not sufficient for the separation of isotopic species. Ike's chapter in the paper notes that while infrared method equipment is simple and inexpensive, it is primarily limited to simple gaseous samples and does not provide information about isotope positions within molecules, and therefore cannot be used for nuclear magnetic resonance (NMrt). It is implied that it is inferior to mass spectrometry and mass spectrometry.

Some of the most promising information regarding the possibility of applying infrared spectroscopy to stable isotope determination of systems in biology or engineering is provided in the following article by Lee et al. That is, [Tuned-pull diode laser spectroscopy of stable isotope tracers - detection and measurement of the abundance ratio of carbon monoxide containing isotopes J, Lee et al.

Abstracts of the 2nd International Symposium on Synthesis and Application of Isotopically Labeled Compounds, pp. 441-446 (1986
); [High-resolution infrared diode laser spectroscopy for isotope analysis - Determination of carbon monoxide with isotopes J, L
ee et al., Applied Physics Letter
s+ Vol. 48, p. 619 (March 1986), U.S. Pat. No. 4,684,805: and "Clinical Spectrum."

5cientific American, 19
December 1987. This study was carried out by Partin
-R, es, Soc.

3ymp, I'roc, Volume 90 (1987)
quoted in. The study shows that infrared spectroscopy using a tunable diode laser and a two-pass measurement cell with one pass tunable yields very accurate results and is useful for measuring isotopic species used in patient clinical trials. It is said to be well suited to The device is presented in a manner that is simpler and much cheaper than previously used mass spectrometry, and could extend the scope of application of tracer methods.

The presented device uses a two-pass sample cell, in which one bus is used to allow simultaneous measurement of two isotopes (generally a naturally occurring abundant isotope and an enrichable trace isotope). It is adjustable, and the isotope ratio can be measured with high precision.The present invention is an extension of this research.

(3) Means for Solving the Problems a. General The object of the present invention is therefore to provide a method for evaluating processes by directly measuring the concentration of isotopically enriched substances using infrared spectroscopy. It is to be.

Another object of the present invention is to provide a method that enables the above measurement without measuring isotope ratios.

Still another object of the present invention is to provide a method that requires only a simple one-pass device, allows very simple sample preparation, and provides results in a short time.

In general, the present invention is achieved by a method for evaluating processes in a system containing substances that are prone to isotope enrichment, which method comprises treating the system of interest with a substance enriched in a tracer isotope. After treatment, a gas sample of the substance containing the tracer species enriched with the tracer isotope is collected from the system, and the gas sample is exposed to monochromatic (single wavelength) radiation having the wavelength of the absorption line for the enriched species. The steps include transmitting and detecting the intensity of spectral lines for the enriched species to determine the enrichment value or concentration of the tracer species in the sample.

The above and other effects of the present invention will become clearer from the following detailed description and the attached drawings.

b. Detailed Description Although the method of the present invention is mainly described with respect to biomedical applications, if one is familiar with the present invention, it should be possible to apply it to industrial process control and engineering tests. Successful application depends on measuring with sufficient precision for the purpose and using relatively inexpensive equipment. A highly sensitive 1-bath infrared spectrometer has been used to detect ultrafine π isotopes in human exhaled breath [
! I! It was shown that a signal with an excellent signal-to-noise ratio suitable for analysis can be obtained. Two spectroscopic methods are presented here for use in the method of the invention, one that is particularly useful for the accurate detection of low-temperature isotopic species, and one that is simple. Suitable for higher concentrations.

One method is second harmonic detection (5econd harmo detection).
This is a method using nicdetection). This method is well known and need not be described in detail.

For details, see the paper by Ileid et al. [Second-harmonic detection using tunable diode lasers - Comparison of experiment and theory J-AI] p1. Phys, Volume B26, 2[
]332210, 1981), so I will list it here as a reference. Figures 1 and 2 - Figure 2 differs only in the enlarged vertical axis - Carbon 1 in CO
2 showing absorption lines at the natural isotope abundance ratio of 2 and carbon-13
The harmonic detection curve is shown. The peak of CO is 17100～
It represents 10/1100pp. These lines were obtained by simply removing water vapor from a person's breath.

The sample was held at a pressure of 3200 Pa (24 torr) and scanned with radiation from a tunable diode laser through a path length of 20 m.

The peak of the line was determined from the calibration curve obtained by calibrating the instrument using standard samples of known concentrations. is very effective, but for higher 61 degree measurements a simpler and more direct method is used, as described below.In both cases no species ratio measurements are required, and in both cases the same basic spectroscopic equipment is used. is used.

A typical apparatus for carrying out measurements using this method is shown in FIG. The device includes a tunable diode laser 10, a power source 12 for the laser 10, and a temperature control section 14. The laser is covered by U.S. Patent 4,350,990 issued to Lo.
and 4,186,355, and 4,577.322 and 4.608,694 to Partin.
It may also be of the sSb type. The wavelength of this laser is determined by changing the operating temperature, and the wavelength is 2.5 to 3
Can be used in the wavelength range of 0 μm. Also, about 0.5 to 30
This narrow band can be scanned at a speed of 500 cycles per second. For example, a wavelength set for a certain absorption peak can be generated without a scanning operation. Alternatively, by performing a scan it is also possible to obtain a total absorption curve associated with a single line to be measured. By changing the applied current, the operating conditions of the laser system can be varied to accommodate various isotopes and molecules. If you use this device.

Any infrared active molecule with the appropriate spectrum can be investigated. Therefore, the device can be used for a single isotope (I
It can be said to be general purpose rather than exclusive. The isotopic spectral lines are well separated and are not subject to background interference as in conventional quality 11 spectroscopy.

The Ga I nAs sb laser mentioned above belongs to short wavelength diode lasers, and is based on the Ga I nAs sb laser of Caneau et al.
19 [ of InAsSb /AlGaAsSb laser
] cw operation at Kt.”

Appl, Phys, Lett, Volume 49, 55
As noted in Hyaku (1986), AJJ, Ga.
In, P, A! It consists of an m-vi compound containing either the elements 1 and sb. These lasers do not emit in the fundamental vibratory-rotating cylinder, but rather in the complex or harmonic band (co) with more sensitive detectors for stable isotope analysis.
mbinationor overtone band
+). Because these short wavelength lasers operate at relatively high heat sink temperatures and are detected with short wavelength infrared detectors, inexpensive coolers such as thermoelectric coolers can be used; or does not require cooling below room temperature.

Yet another laser source is a band-array grating laser, which could potentially be fabricated for room temperature operation. This type of laser is described in Yuh et al.'s "New Infrared Band Array Superlattice Laser J, Appl, Ph.

Lett, Vol. 51, p. 1404 (1987).

Laser radiation is transmitted through a chopper (interrupter) 13 and a lens system 18
and reaches the spectroscopic grating 20, where it passes as a single optical mode. The laser is tuned so that this mode contains the absorption line of the isotope molecule of interest. The radiation (light) then passes through a cell 22 containing the sample gas. The detection unit 28 is the cell 2
The signal processing unit processes the detection signal and displays the result on the display unit 32. When using the second harmonic detection method, the chopper can be omitted and the input current is changed to modulate the radiation (light).Furthermore, a signal processor is provided to analyze the signal according to the second harmonic detection. In carrying out the method of the present invention, changes may be made to the basic equipment.For example, in the curve of Fig. 2, the slight noise observed on the baseline is mainly due to optical noise caused by the reflective optical system. This noise source can be eliminated by replacing the lens with an off-axis parabolic mirror. In this way, very low concentration conspecific species can be measured without noise interference. For single mode operation, the spectroscopic grating can also be omitted.

For example, in biological or engineering tests.

Often we measure substances that have passed through a subject or system, or that have undergone a process that involves a chemical change. According to the present invention, by enriching the target substance with stable isotopes of its molecular components, the amount of the substance that has passed through other parts of the system or has undergone chemical or biological changes can be reduced. It can be measured as the absolute ε4 degrees in a sample taken from a subject. Measurements are made on a single absorption line in the tracer isotope spectrum. This line is carried from an area free from interference from other species,
The sample does not require any treatment other than water vapor removal, nor does it need to be kept at low pressure to avoid pressure-induced broadening of the spectral lines. It is not necessary to measure the ratio of enriched substances to other substances, as is the case with isotope ratio spectroscopy. Furthermore, the concentration can be measured directly from the radiated and incident intensities at the location of the spectral lines. Possible errors in calculating concentrations from ratio measurements are also avoided.

In biomedical tests, a subject is administered isotopically enriched substances or tracer substances, which are deposited in the tissues or excreted after undergoing physiological processes. The tracer used in this test is often one that is converted into carbon dioxide, carbon oxide, ammonia or water and is excreted in the exhaled breath. Therefore, exhaled breath from the subject is collected as a sample. (Except when the water vapor itself is the test object in order to remove water vapor in the sample), the sample is
The sample cell is placed at a low pressure of 00 I'a (24 torr). Radiation with a wavelength corresponding to the absorption line of the target isotope tracer species is transmitted through the cell, and the intensity (■) after transmission is measured. When determining the absolute concentration, use the incident intensity■. It is necessary to measure ■. is obtained by evacuating the cell and measuring the intensity of the same wavelength transmitted through it. As shown in Figure 4, the incident intensity ■. Another way to find the radiation is to get it as close to an absorption line as there is no absorption by that line! The intensity may be measured by adjusting the wavelength f0 of . The concentration of the tracer species is determined from the 13eer-Lambert law. That is, I=I. e, where p is the partial pressure of the isotope molecule (torr) and l is the path length (cm
), a is the spectral absorption coefficient of the isotope molecule. In the case of breath samples, the isosterically enriched substances are often enriched with carbon-13, oxygen-18 or nitrogen-15, and the tracer species is usually carbon dioxide, -carbon oxide, water or ammonia. and,
Other isotopes f! 1! Two types of concentration measurement methods are applicable regardless of the Which one to apply depends on the target physiological process.

As shown in U.S. Pat. No. 4,684,805, C
In one study using O2, researchers ingested O2 (0,) or nitrogen dioxide (No,) labeled with oxygen 18, collected a gas sample containing CO from one tissue, and quantified the tracer deposited there. /C''0 ratio is measured to determine the enrichment ratio in the sample.According to the present invention, it is possible to directly measure the CO concentration while measuring CO. is introduced into the cell and one of the concentration measurement methods is applied to directly measure the tracer concentration in the sample.

The well-known glucose tolerance test typically involves taking a series of white liquor samples after ingesting a certain amount of glucose.

It is analyzed and the results are obtained after a certain amount of time.

According to the present invention, a simpler test is possible, especially from the standpoint of the subject, and results can be obtained almost immediately. The glucose ingested by the subjects was labeled with carbon-13,
First, the breath of the Sugi tester is collected as a standard sample, and breath samples are collected periodically as the labeled glucose is ingested orally. Labeled glucose is a precursor to exhaled carbon dioxide, and samples are measured to quantify the carbon-13 isotope species in exhaled breath. Water is removed from each sample, usually by freezing or absorption, and the absolute concentration of marked CO7 is measured within a few minutes. The concentration in each sample is representative of the physiological changes in glucose, which is reflected in CO2 from other sources.
is unrelated to the existence of

The enrichment of each sample can be determined by simple comparison with standard samples.

As described above, the method of the present invention makes it possible to investigate processes by directly measuring isotope species independently of other species in the sample using stable isotope tracers. . This method utilizes known equipment that is relatively inexpensive, and can be applied to clinical trials across all medical fields. Industrial applications are also possible.

This method requires less sample preparation, especially when gaseous samples are used, and results can be obtained in a short time.

Moreover, in physiological applications, it almost always has no adverse effects.

[Brief explanation of the drawing]

Figures 1 and 2 show 1 measured by the method of the present invention.
FIG. 2 is a diagram showing spectral lines of carbon monoxide in human exhaled breath. Both figures differ in the scale of one vertical song. FIG. 6 is a block diagram of an apparatus for carrying out the method of the present invention. FIG. 4 is a graph showing the line intensity of a high-resolution spectrum of the same grade. (4 other people) 2031.005 2031.632 Fu2U! J 1 Atsushi [Cm-1] No. 47 2゜3゜Procedural amendment August 70, 1989 Patent application No. 117147 of 1999 Name of the invention Person who amends process evaluation method by isotope enrichment Relationship with the case Patent Applicant Address Name General φ Motors φ Corporation Shin-Otemachi Building 206 Ward 6 Contents of Amendment 1: The name of the invention is changed as follows. "Process evaluation method using isotope enrichment" 2, the claims are amended as in the attached sheet. 3. In the detailed description of the invention, (1) "Enrichment (concentration)" on page 7, line 13 is corrected to "concentration," (2) Page 11, line 1, page 12, line 13. , page 15, line 2 from the bottom, page 13, line 7, page 22, line 3, 22
"Enrichment" in line 13 of page 13, lines 3-2 from the bottom of page 22, line 1 of page 24, line 13 of page 24, and line 7 from the bottom of page 25 has been corrected to "concentration." , (3) Change "enriched with" to "
It is corrected as "concentrated". Attachment 1. A method for evaluating processes in a system containing a substance susceptible to isotope enrichment, that is, 2. Treating the above system with a substance enriched with tracer isotopes; A method comprising the steps of: preparing a gaseous sample of a system of matter containing an enriched tracer species; and further analyzing the gaseous sample to determine the amount of the tracer isotope present, the method comprising: is maintained at a pressure that allows the absorption lines of the tracer species to be distinguished from those of the associated isotope species; monochromatic radiation at the frequency of the absorption line for the enriched species is transmitted through the gaseous sample; A method characterized in that it comprises a step of detecting spectral line intensities for enriched species in a sample in order to determine the enrichment value of tracer species. 2. Evaluating processes in systems involving substances susceptible to isotopic enrichment. 2. A method according to claim 1, comprising: determining the level of incident radiation by transmitting radiation at a frequency slightly away from the absorption line through the sample and detecting the incident intensity; and determining the enrichment value from the relative detected intensity. 3. The method according to claim 1, which evaluates a process in a system containing a substance susceptible to isotope enrichment, comprising: detecting radiation in the absence of an absorbing sample; 4. The method according to claim 1, characterized in that the reference value of the intensity is determined by calculating the enrichment value from the ratio of the intensities. wherein the transmission procedure comprises modulating a radiation frequency and varying the radiation frequency across an absorption line of the concentrated species;
and the detection step includes harmonic detection of the transmitted radiation. 5. The method according to claim 1, for evaluating a process in a system containing a substance susceptible to isotopic enrichment, wherein a reference gas sample of a substance that is not quantitatively enriched in tracer species is used prior to the enrichment treatment. performing a transmission and detection procedure to determine a reference spectral line intensity for the tracer species; and determining an enrichment value from the difference between the reference spectral line intensity and the enriched spectral line intensity. . 6. The method of claim 1 for evaluating a process in a system containing a substance susceptible to isotope enrichment, the method comprising: taking a plurality of enriched samples at different times or locations;
A method characterized in that the enrichment values are measured in order to determine variations in the enrichment amount. 7. The method according to claim 1, wherein the method evaluates a process in a system containing a substance susceptible to isotope enrichment, the method being a method for evaluating the physiological function of a subject using a stable isotope tracer; : Administering to a subject an isotopically enriched substance that is subject to physiological function and is ultimately excreted in the exhaled air as an isotopically enriched gas mass; after the treatment, the subject taking a breath sample from; keeping the pressure of the gas sample low enough to distinguish between the absorption lines of the enriched species and the associated isotopic species; A method comprising the steps of: transmitting monochromatic radiation through the breath sample; and measuring spectral line intensities proximate to the enriched species to determine the concentration of the enriched species in the sample. 8. The method according to claim 1, wherein the method evaluates a process in a system containing a substance susceptible to isotope enrichment, the method is a method for evaluating the physiological function of a subject using a stable isotope tracer; : Administering to a subject an isotopically enriched substance that is subject to physiological function and is deposited as an enriched species in a biological sample; after treatment, the isotope tracer enriched species is extracted from the sample. prepare a gas sample containing; maintain the pressure of the gas sample low enough such that the absorption lines of the enriched species and the adjacent isotopes can be distinguished as described above; A method characterized in that it comprises the steps of: transmitting said monochromatic radiation having a frequency of a line through said gaseous sample; and detecting the intensity of adjacent spectral lines. 9. The method of claim 8 for evaluating a process in a system containing a substance susceptible to isotopic enrichment, wherein the stable isotope is carbon-13 and the enriched species in the gas sample is carbon-13 enriched. A method characterized in that carbon dioxide. 10. The method according to claim 8, wherein the stable isotope tracer is a low-abundance isotope of carbon or oxygen, and the stable isotope tracer is a low-abundance isotope of carbon or oxygen. A method characterized in that the species is carbon dioxide. 11. The method of claim 8 for evaluating a process in a system containing a substance susceptible to isotopic enrichment, wherein the stable isotope is oxygen-18 and the enriched species in the gas sample enriches oxygen-18. A method characterized in that water vapor is used. 12. The method of claim 8 for evaluating a process in a system containing a substance susceptible to isotopic enrichment, wherein the stable isotope is nitrogen-15 and the enriched species in the gas sample enriches nitrogen-15. A method characterized in that it is ammonia. 13. The method according to claim 8, wherein the method evaluates a process in a system containing a substance susceptible to isotopic enrichment, wherein the method evaluates a physiological process of a subject by infrared spectroscopic analysis of the enriched species. , which: prepares a material enriched with a tracer isotope that is a precursor of the enriched isotopic species to be measured; obtains a first gas sample from the subject; passing through the gas sample; detecting the spectral line intensity after transmission to measure the concentration of isotope species in the sample; administering the isotope-enriched substance to the subject and then collecting a second gas sample from the subject; repeating the transmission and detection procedure for a second sample; and determining the influence of physiological processes on the concentrated substance by comparing measurements of the isotope concentration in the first and second gaseous samples. A method characterized by comprising a step of clarifying. ”

Claims (1)

[Claims] 1. A method for evaluating a process in a system containing a substance susceptible to isotope enrichment, namely: treating the system with a substance enriched with a tracer isotope; after the treatment, producing a gaseous sample of the material of the system containing a tracer species enriched with the tracer isotope from the system; and further steps of analyzing the gaseous sample to determine the amount of the tracer isotope present. a method comprising: holding the gaseous sample at a pressure that allows the absorption lines of the tracer species to be distinguished from absorption lines of a nearby isotopic species; emitting monochromatic radiation at the frequency of the absorption line for the enriched species; A method comprising: transmitting the gas to the sample; and detecting the spectral line intensity for the enriched species in the sample to determine the enrichment value of the tracer species in the sample. 2. The method according to claim 1, for evaluating a process in a system containing a substance susceptible to isotopic enrichment, the method comprising transmitting radiation at a frequency slightly away from the absorption line through the sample and detecting the incident intensity. and determining an enrichment value from the relative detected intensities. 3. The method according to claim 1, which evaluates a process in a system containing a substance that is susceptible to isotope enrichment, wherein radiation is detected in the absence of an absorbing sample, and the enrichment value is determined from the ratio of detected intensities. A method characterized in that a reference value of intensity is determined by calculating . 4. The method of claim 1 for evaluating a process in a system containing a substance susceptible to isotopic enrichment, wherein the transmission step comprises modulating a radiation frequency and directing the radiation frequency to that of the enriched species. including changing across the absorption line,
and the detection step includes harmonic detection of the transmitted radiation. 5. The method according to claim 1, which evaluates a process in a system containing a substance susceptible to isotopic enrichment, wherein the reference of the substance is not quantitatively enriched in tracer species prior to the enrichment treatment. preparing a gas sample; performing a transmission and detection procedure to determine a reference spectral line intensity for the tracer species; and determining an enrichment value from the difference between the reference spectral line intensity and the enriched spectral line intensity. A method characterized by: 6. The method of claim 1 for evaluating a process in a system containing a substance susceptible to isotopic enrichment, comprising taking a plurality of enriched samples at different times or locations;
A method characterized in that the enrichment values are measured in order to determine variations in the enrichment. 7. The method according to claim 1, which evaluates a process in a system containing a substance susceptible to isotope enrichment, wherein the method evaluates the physiological function of a subject using a stable isotope tracer. , which: administers to a subject an isotopically enriched substance that is subject to physiological function and is ultimately excreted in the exhaled breath as an isotopically enriched gaseous species; a breath sample is then collected from the subject; the pressure of the gas sample is kept low enough to distinguish the absorption lines of the enriched species from the isotopic species of interest; transmitting said monochromatic radiation having an absorption line frequency through said breath sample; and measuring the spectral line intensities proximate to the enriched species to determine the concentration of enriched species in the sample. A method characterized by: 8. The method according to claim 1, which evaluates a process in a system containing a substance susceptible to isotope enrichment, wherein the method evaluates the physiological function of a subject using a stable isotope tracer. , which: administers to a subject an isotopically enriched substance that is subject to physiological function and is deposited as an enriched species in a biological sample; after its treatment, the isotope tracer is removed from the sample; preparing a gaseous sample containing an enriched species; maintaining the pressure of the gaseous sample low enough so that the absorption lines of the enriched species and the adjacent isotopic species can be distinguished as described above; a method comprising: transmitting said monochromatic radiation having a frequency of an absorption line of an enriched species through said gaseous sample; and detecting the intensity of adjacent spectral lines. 9. The method according to claim 8, for evaluating a process in a system containing a substance susceptible to isotopic enrichment, wherein the stable isotope is carbon-13 and the enriched species in the gas sample is carbon-13. A method characterized in that the carbon dioxide is enriched with carbon dioxide. 10. The method according to claim 8, wherein the stable isotope tracer is a low-abundance isotope of carbon or oxygen, and the stable isotope tracer is a low-abundance isotope of carbon or oxygen. A method characterized in that the enriched species is carbon dioxide. 11. The method of claim 8, wherein the stable isotope is oxygen-18 and the enriched species in the gaseous sample is oxygen-18. A method characterized in that the water vapor is enriched with 12. The method of claim 8, wherein the stable isotope is nitrogen-15 and the enriched species in the gaseous sample is nitrogen-15. A method characterized in that the ammonia is enriched with ammonia. 15. The method of claim 8, wherein the method assesses a process in a system containing a substance susceptible to isotopic enrichment, wherein the method assesses a physiological process in the subject by infrared spectroscopy of the enriched species. The method is: preparing a substance enriched with a tracer isotope that is a precursor of the enriched isotopic species to be measured; obtaining a first gas sample from a subject; absorbing the isotopic species to be measured. transmit infrared radiation having a frequency of detecting the physiological A method comprising the step of determining the effect of a process on the enriched substance.