EP1996920A1

EP1996920A1 - Apparatus for spectroscopically analysing a gas

Info

Publication number: EP1996920A1
Application number: EP07723482A
Authority: EP
Inventors: Martin Stockmann; Björn RIECKE; Karsten Heyne
Original assignee: Charite Universitaetsmedizin Berlin; Freie Universitaet Berlin
Current assignee: Charite Universitaetsmedizin Berlin; Freie Universitaet Berlin
Priority date: 2006-03-17
Filing date: 2007-03-16
Publication date: 2008-12-03
Also published as: AU2007228959A1; DE102006018862A1; US20090124918A1; CA2645445A1; WO2007107366A1; AU2007228959B2

Abstract

The invention relates to an apparatus for spectroscopically analysing a gas, said apparatus having at least one radiation source (1), at least one detection apparatus (12; 20), at least one sample chamber (13) and a system of optical elements (4; 5; 6; 7; 9; 10; 11; 18; 19) which is intended and set up to direct at least part (3b) of the radiation (3) emitted by the radiation source (1) through the sample chamber (13) onto the detection apparatus (20), wherein the sample chamber (13) is used to hold a gaseous sample which contains the gas to be analysed, and wherein the apparatus is configured in such a manner that the sample can continuously flow through the sample chamber (13), and means (16) are provided for the purpose of determining the pressure and/or the volume and/or the concentration of the sample in the sample chamber (13). The invention also relates to a corresponding method for spectroscopically analysing a gas.

Description

Device for the spectroscopic analysis of a gas

The invention relates to a device for spectroscopic analysis of a gas according to the preamble of claim 1, a method for the spectroscopic analysis of a gas according to the preamble of claim 18 and the use of a device according to the invention according to the preamble of claim 28.

The analysis of a gas has a variety of applications, especially in medicine. The concentration of ¹³ CO _2, for example, in the exhaled air of patients who were previously administered ¹³ C-labeled substances that are metabolized by the body and lead to the production of ¹³ CO ₂ ( ¹³ C-breath tests) is often examined. Such studies are useful, for example, for the diagnosis of Helicobacter pylori, for measurements of gastric emptying time or for liver function tests.

The ¹³ CO ₂ concentration is determined in the prior art by mass spectrometry, Fourier transform infrared spectrometry or by direct inorganic chemical analysis. The use of said techniques usually requires a great deal of expensive equipment or structures that can not be used directly on the patient. For this reason, non-dispersive isotope-selective infrared spectroscopy (NDIRS) (eg Fischer Analyzes Instruments, Leipzig) and a method based on infrared emission and absorption (LARA) are also used in the prior art. However, both methods measure only relative ¹³ CO ₂ - concentration changes and do not allow absolute ¹³ CO ₂ concentration measurement. For the latter two methods, an estimated total CO ₂ production rate of one to calculate the relative ¹³ CO ₂ concentration changes investigated without being able to accurately determine the actual total CO ₂ production rate.

The method of NDIRS is sensitive enough to measure, for example, the relative ¹³ CO ₂ concentration changes in the exhaled volume of patients, but shows strongly deviant and therefore difficult to use results for different carrier gas mixtures (eg O ₂ ) and allows only a very slow by their slow measurement method limited resolution of ¹³ C metabolism. The measurement accuracy of the NDIRS is also limited and especially for direct quantitative measurements such as the determination of the quantitative liver function capacity, especially not sufficient, if other measurement influences such as changing carrier gases to occur (Perri, F., RM Zagari, et al. (2003) Inter- and intra-laboratory comparison of breath ¹³ CO ₂ analysis. "Aliment. Pharmacol. Ther. 17 (10): 1291-7). Furthermore, NDIRS devices are not mobile.

Furthermore, it is methodologically partially effective only the ¹³ CO _^2/12 CO ₂ ratio is determined. From this, the absolute amount of exhaled ¹³ CO ₂ per unit time can be calculated with the aid of the total CO ₂ production rate per minute of the patient. However, the CO ₂ production rate can only be measured with great difficulty in a single individual. The prior art therefore uses for calculation an estimated standard value of the CO ₂ production rate which is respectively adapted to the body surface of the individual (Schoeller, DA, JF Schneider, et al. (1977). "Clinical diagnosis with the stable isotope ¹³ C in CO2 breath tests: methodology and fundamental considerations. "J. Lab. Clin. Med. 90 (3): 412-21; Schoeller, DA, PD Klein, et al. (1981)." Fecal ¹³ C analysis for the detection and quantitation of intestinal malabsorption. "J. Lab. Clin. Med. 97 (3): 440-8). This procedure requires significant inaccuracy in many clinical situations where the individual's CO ₂ production rate is altered from normal.

US 2004/0211905 A1 describes a respiratory analyzer in which parts of exhaled respiratory air are introduced via a gas transfer system into a spectrometer for analysis. In this analyzer, only the relative ratio of two isotopes of a gas to each other can be determined, but not the absolute concentration of a

Isotopes alone. By using the gas transfer system, preferably not all of the exhaled air is expelled, but only portions thereof are introduced into the spectrometer. US Pat. No. 6,186,958 describes a respiratory analyzer which is designed for online analysis of continuously exhaled breath. This analyzer can distinguish between individual isotopes of gas through the use of multiple gas discharge lamps, each filled with only one isotope of gas to be analyzed. However, only the relative ratio of the individual isotopes of the gas to each other can be determined by means of this analyzer. This is based in particular on the fact that the concentration of the air to be analyzed in a sample chamber of the analyzer can not be determined.

The present invention was based on the problem to provide a device which is suitable for determining the absolute concentration of a gas in a gas mixture; To develop a method by which such a determination is made and to provide a suitable use for a device according to the invention.

This problem is solved by a device having the features of claim 1, a method having the features of claim 18 and the use of a device according to the invention having the features of claim 28.

Such a device for the spectroscopic analysis of a gas has at least one radiation source, at least one detection device, at least one sample chamber and a system of optical elements, which is provided and arranged for this, at least a part of the radiation emitted by the radiation source through the sample chamber to the detection device guide, wherein the sample chamber for receiving a gaseous sample containing the gas to be analyzed, is used. This device is characterized in that it is designed such that the sample can flow through the sample chamber continuously, and that means are provided for determining the pressure and / or the volume and / or the concentration of the sample in the sample chamber.

Such means may be, for example, a pressure gauge or a volume meter, optionally in conjunction with a temperature gauge.

The system of optical elements consists of lenses, mirrors, filters and beam splitters and comparable elements, the number and sequence of which in the beam path of the device being freely selectable, provided that the desired steering effect is achieved. As a rule, only as many optical elements are used as are necessary for the best possible performance of the device. In a preferred embodiment of the invention, the device for the spectroscopic analysis of a gas is designed so that essentially only an absorption of a single isotope of the gas is excited by the emitted radiation and / or detected by the detection device.

In order to achieve this, the emitted radiation preferably passes through a filter which is continuous only for radiation in the desired wavelength range. Furthermore, a narrow-band detection device is preferably used which is particularly sensitive in the wavelength range to be analyzed and whose detection power is not significantly influenced by any incident radiation having a different wavelength. In addition, it is preferable to use a radiation source which emits only radiation in a narrow wavelength range, so that substantially no absorption other than the desired absorption is excited. The aforementioned functional elements can be used individually or in any combination in a device according to the invention, in order to enable the substantially isotope-selective excitation.

In order to enable a high information density of the gas analyzes carried out by means of the device, the device is preferably designed in such a way that the spectroscopic analysis of the gas takes place in a time-resolved manner. For this purpose, preferably a radiation source is used, which emits pulsed light or a chopper positioned in the beam path, which can convert a continuous radiation by interruptions of the light beam into a radiation with a defined repetition rate.

The time resolution is preferably better than 1 second, and more preferably between 0.2 and 0.4 seconds (for example, 0.3 seconds or better). With a preferred embodiment of the invention, therefore, more than 3 measurements per second can be performed, resulting in a fine screening of a time course of the analysis performed.

In particular, since molecular vibrations are to be studied, the radiation source preferably emits light having a wavelength from the infrared region, with the middle infrared being particularly preferred. The middle infrared light has a wavelength of about 2.5 to 50 μm (corresponding to 4000 to 200 cm ^-1 ).

In order to emit pulsed radiation of high energy density and brilliance from the radiation source, a quantum cascade laser is preferably used. O

For an application of the device according to the invention for the investigation of ¹³ CO ₂ absorptions, which represents a preferred use of the invention, it is preferable to use a quantum cascade laser which emits light from a wavenumber range of about 2280 to 2230 cm ^-1 . In this wavenumber range, the P branch of ¹³ absorbs CO ₂ in the gas phase, while virtually no other interfering absorptions of about ¹² CO ₂ , H ₂ O or O ₂ can be observed.

For a sensitive and specific absorption of the preferably investigated ¹³ CO ₂ bands, a photovoltaic mercury cadmium telluride detector (MCT detector) is preferably used, which does not require cooling by liquid nitrogen. A detection maximum of the detector of approximately 2270 cm ^-1 is advantageous.

Since ¹³ CO _{2 has} only a small but undisturbed absorption in the preferably examined spectral range, a large number of mirrors is arranged in the sample chamber, which reflects the light beam injected into the sample chamber back and forth several times within the sample chamber. As a result, the beam path to be traveled by the light beam is increased many times, thus fictitiously increasing the amount of the gas under investigation. This

Method can also be applied to other substances that have only a low extinction coefficient in each examined area.

Preferably, the mirrors are arranged such that the beam path to be traveled by the light beam within the sample chamber is longer than 1.5 m and up to 2.5 m or longer. By contrast, the sample chamber itself is only a few centimeters or decimetres tall.

Preferably, the sample to be examined is respiratory air containing the gas to be analyzed. The breathing air is preferably exhaled directly from an individual into the device, so that the breathing air is exhaled air.

The gas to be analyzed is ¹³ CO ₂ in a preferred embodiment of the invention.

The transfer of exhaled breath or other sample is preferably by means of a tube which is heated in a preferred embodiment to prevent water from collecting in the tube and to ensure that the gas temperature remains constant. To ensure reliable operation of the device, it is preferably designed such that only specially developed D

Hoses can be connected to the device. If necessary, use a first adapter for the connection. If breathing air is to be analyzed as a sample, it is expedient to provide the hose with a second adapter in the form of a mouthpiece in order to allow a simple injection of breathing air into the hose.

So that the sample which has flowed into the sample chamber can also leave the sample chamber again, it is preferably provided with a gas outlet means, which mediates the sample to flow out of the sample chamber. The gas outlet means is designed such that it allows only an outflow of the sample or another substance from the sample chamber, but not an inflow of sample or substance into the sample chamber. The gas outlet means may, for example, be designed so that it opens at a certain pressure in the sample chamber and sample can flow out of the sample chamber. This pressure can be only slightly greater than the normal ambient air pressure.

A method according to the invention for the spectroscopic analysis of a gas comprises the following steps: introduction of a sample containing the gas to be analyzed into a sample chamber in which the sample flows into the sample chamber, the sample chamber allowing a later outflow of the sample from the sample chamber a portion of a radiation emitted by a radiation source through the sample chamber to a detection device by means of a system of optical elements for analyzing the gas and detecting absorption of the radiation by the gas to be analyzed by means of the detection device. Such a method is characterized in that a change in the pressure and / or the volume and / or the concentration of the sample in the sample chamber during the spectroscopic analysis is determined by suitable means.

Preferably, essentially only an absorption of a single isotope of the gas is excited by the emitted radiation and detected by the detection device. In conjunction with the determination of the change in pressure, volume or concentration of the sample in the sample chamber during the analysis, the absolute concentration of an isotope of the gas can be determined.

In a preferred application of the method, the spectroscopic analysis is time-resolved in order to obtain analytical measured values as a function of time. For example, changes in the concentration of the gas to be analyzed can be determined over the course of the analysis. The time resolution is preferably better than about 1 second and more preferably between 0.2 or 0.4 seconds (about 0.3 seconds or better). With such a time resolution, even rapid metabolic processes can still be studied in detail without the fear of significant loss of information due to averaging or non-detection of different states due to excessively long measurement intervals.

Preferably, absorption of the gas to be analyzed is detected in the mid-infrared range, with detection in the wavenumber range of 2230 to 2280 cm ^{-1 being} particularly preferred.

In a preferred embodiment of the invention, the sample to be examined is exhaled breathing air, the gas to be analyzed preferably being ¹³ CO ₂ .

The breathing air is preferably introduced into the sample chamber with a tube which is heated in order to prevent condensation of gaseous constituents of the sample on the tube inner wall or local deposition of liquid portions of the sample and to ensure temperature control of the sample.

In a preferred embodiment of the invention, the outflow of the sample from the sample chamber is effected by an outlet means, which prevents substances from entering the sample chamber. The outlet means thus allows an exclusive sample transport out of the sample chamber.

A device according to the invention lends itself to the determination of a biological parameter of an individual, in particular of a human being, for which purpose a spectroscopic analysis of a gaseous sample originating from the individual is carried out. In particular, exhaled air is considered as a gaseous sample. The sample is analyzed outside the body of the individual.

The biological parameter is preferably the function of an organ of the individual, with function and capacity determinations of the liver and pancreas being particularly preferred.

In a variant of the invention, the device can also be used to determine the concentration of an enzyme, such as the lactase, by means of analysis of the To determine respiratory air of the individual and thus to be able to draw conclusions on enzyme deficiency states of the individual.

In a further variant of the invention, the device can also be used to determine the concentration of a microbial species such as a particular bacterium, a virus or a fungus in an organ or tissue of the individual. This may preferably be the determination of the Helicobacter pylori concentration in the stomach of the individual.

Further advantages and details of the invention will be explained in more detail with reference to drawings. Show it:

1 shows a schematic representation of the structure of an inventive

Device for the spectroscopic analysis of a gas,

FIG. 2 is a diagram for calculating a difference signal from signals detected by a device according to FIG. 1, and FIG

Fig. 3 is a schematic representation of possible courses of ¹³ CO ₂ concentration in exhaled breath.

FIG. 1 shows a schematic representation, not to scale, of an infrared spectrometer as an exemplary embodiment of a device according to the invention for the spectroscopic analysis of a gas.

The infrared spectrometer has a radiation source 1 in the form of a laser or a globar and a driver 2 for the radiation source 1, which is electronically connected to the radiation source 1. The radiation source 1 emits radiation in the form of a light beam 3 which has a wavelength in the mid-infrared range. After its exit from the radiation source 1, the light beam 3 initially strikes a cylindrical lens 4, which ensures a parallel propagation of the light beam 3. After a variable distance, it strikes a first lens 5, which is arranged on the same optical axis as the cylindrical lens 4 and focuses the light beam 3 onto a second lens 6, which likewise is arranged on the same optical axis as the cylindrical lens 4 and the first lens 5 is. The second lens 6 ensures a highly concentrated, substantially parallel propagation of the light beam 3. In the further course of its propagation, the light beam strikes a filter 7, which is continuous only for the part of the light beam 3 which is to be used for the detection of a sample. In this embodiment, the filter 7 is an infrared narrow band filter which passes only light having a wavelength corresponding to a wave number of about 2260 ± 20 cm ^-1 .

Between the second lens 6 and the filter 7, a chopper 8 is arranged, which is used in particular when a globar is used as the radiation source 1. While a laser can emit radiation already pulsed, the radiation emitted by a globar is a continuous unpulsed radiation. By the chopper 8, which is electronically connected to the driver 2 of the radiation source 1, the radiation emitted by a Globar radiation can be pulsed.

The radiation emitted by a preferably used quantum cascade laser has a repetition rate of 10 kHz. If a globar is used instead of the laser, a repetition rate of about 10 kHz is set via the chopper 8.

After the light beam 3 has passed the filter 7, it encounters a beam splitter 9 which divides the light beam 3 into a first partial beam 3a and a second partial beam 3b. The first partial beam 3a is deflected by the beam splitter by 90 °, while the second partial beam 3b passes through the beam splitter in extension of the original propagation direction of the light beam 3. The first partial beam 3a is directed by means of a deflection mirror 10 and a third lens 11 to a first detector 12, which detects the intensity of the first partial beam 3a.

The second partial beam 3b is conducted into a sample chamber 13. The sample chamber 13 is filled with a gaseous sample which is supplied to the sample chamber 13 via a gas inlet 14 in the arrow direction and which can leave the sample chamber 13 through a gas outlet 15 in the direction of the arrow. The gas outlet 15 is designed such that no gas can enter the sample chamber 13 through the gas outlet. By means of a gas flow meter 16, the gas volume supplied to the sample chamber 13 through the gas inlet 14 is measured, so that the amount of gas that is in the sample chamber 13, is always known exactly. The gas flow meter 16 is electronically connected to a computer 17 and can thus transmit the data determined by him to the computer 17.

In the sample chamber 13, a system of a plurality of mirrors 18 is arranged, which deflect the second part of the beam 3b so within the sample chamber 13 and that the Beam path of the second partial beam 3b is extended in the sample chamber relative to the actual longitudinal extent of the sample chamber 13. Finally, one of the mirrors deflects the second partial beam 3b out of the sample chamber. After passing through a fourth lens 19, the second partial beam 3b strikes a second detector 20, from which the intensity of the second partial beam 3b is detected.

Because the intensity of the first partial beam 3a, which experiences no attenuation by an absorbing substance, is always measured parallel to the intensity of the second partial beam 3b, which is attenuated by the absorption of the sample in the sample chamber 13, smaller intensity differences of the radiation source 1 emitted radiation 3 are compensated. In this way measurement errors that might arise due to such smaller intensity differences are avoided.

The first detector 12 is electronically connected to a first lock-in amplifier 21 and to a second lock-in amplifier 22. The second detector 20 is connected to the second

Lock-in amplifier 22 electronically connected. Both lock-in amplifiers 21 and 22 serve to amplify the relatively weak detected by the two detectors 12 and 20

Intensity signals of the two partial beams 3a and 3b. The two lock-in amplifiers are part of an electronic component assembly of the infrared spectrometer, including the driver 2 of the radiation source 1, the chopper 8, the gas flow meter 16, the first

Detector 12, the second detector 20 and the computer 17 belong.

Within the electronic component network, the chopper 8 is electronically connected directly to the driver 2 of the radiation source 1, the first detector 12, the first lock-in amplifier 21, and the second lock-in amplifier 22. Further, the first lock-in amplifier 21 and the second lock-in amplifier 22 are directly connected to each other and the computer 17. The respective electronic connections are used for data transmission and synchronization of the individual components with each other. The computer 17 serves to display and evaluate the determined data.

By using pulsed light with a repetition rate of about 10 kHz, it is possible to detect lock-in amplified signals with a time resolution of about 0.3 seconds. The advantages of such a time resolution are explained in more detail in the description of FIG.

To determine the ¹³ CO ₂ content in a sample, an infrared narrow-band filter is used as the filter 7, which determines the proportion of infrared light passing through the filter can be limited to those wavelengths in which ¹³ CO ₂ shows characteristic absorption bands. This is preferably the wavelength range which corresponds to wavenumbers of 2280 to 2230 cm ^-1 . It is also possible to use a filter which passes only light from a wavelength range corresponding to wavenumbers of 2282 to 2250 cm ^-1 .

The first detector 12 and the second detector 20 are each a photovoltaic mercury cadmium telluride detector (MCT detector) having a peak response of 1.6 A / W. These MCT detectors, unlike conventional MCT detectors, do not need to be cooled with liquid nitrogen. The cooling is done rather by means of a Peltier element. With an average power of a laser as a radiation source 1 of about 0.3 mW distributed to 40 cm ^'1 , results in a Messsigπal of a few hundred uA. The noise of each of the two lock-in amplifiers 21 and 22 is in the pA range and thus far away from the signal range. The signal can still be - without coming into the noise area - greatly attenuated.

On the basis of an absorption of ¹³ CO ₂ with an absorption coefficient of ε = 30 m ² / mol and a concentration of ¹³ CO ₂ of about ^{1.4 x} 10 ^-4 mol / m ³ in normal ambient air, a ¹³ CO ₂ estimate conditional absorption of about 0.0042 per meter. Therefore, the beam path in the sample chamber 13, in which the gas is located, several meters (preferably 1, 5 to 2.5 m) to ensure sufficient absorption of the incident second partial beam 3b by the ¹³ CO ₂ .

Compared with the prior art, the following advantages and improvements are achieved by a device according to the invention, as described in FIG. 1:

It is possible to carry out measurements of the absolute concentration of a gas per time interval.

The concentration measurement is faster, so that a faster evaluation of the data is possible.

Data security is higher due to less susceptibility to fluctuations.

Concentration changes can be tracked directly in real time.

The flow measurement technology allows a continuous measurement of the gas samples. - The measurement of the ¹³ CO ₂ concentration is independent of the ¹² CO ₂ concentration.

The measurement results are independent of most carrier gases. So can as

Carrier gases also gases used in anesthesia, can be used. The device can be used directly on a patient. A compact design makes mobile use possible.

Accurate measurement of the ¹³ CO ₂ concentration and no estimation of the CO ₂ production rate allow for more accurate quantitative statements (eg quantitative information on liver function capacity)

FIG. 2 shows in conjunction with and with reference to the infrared spectrometer shown in FIG. 1 a scheme for calculating a difference signal S _D from two individual signals D ₁ and D ₂ detected by the first detector 12 and the second detector 20 , Numerical reference numbers refer to FIG. 1, letters as reference numbers refer to FIG. 2.

Only about 1% of the infrared light radiated into the sample chamber 13 as the second partial beam 3b is absorbed at the absorption wavelengths of the ¹³ CO ₂ . On this signal an absorption change of less than 1% should be measured. This is done by measuring the signal D _{1 of} the first detector 12 and the signal D _{2 of} the second detector 20 with subsequent difference Δ. Since the two detector signals D ₁ and D _{2 are} much larger than their difference S ₀ , only a first sub-signal S ₁ or S ₂ , the few percent (preferably about 2%) of the signal D ₁ or D ₂ for direct measurement includes, used. This division of the signals D ₁ and D ₂ into a respective first sub-signal S ₁ or S ₂ and a second sub-signal S ₃ or S ₄ takes place through the use of two voltage dividers ST ₁ and ST ₂ .

The difference signal S _D is measured with the sub-signals S ₃ and S ₄ , which respectively comprise the main components of the detector signals D ₁ and D ₂ . The two signals S ₁ and S ₀ are connected to the first and second lock-in amplifiers 21 and 22 (or alternatively in a

Single-shot measurement with integrating preamplifiers) and amplified by an analogue

Digital converter in the computer 17 converted into digital signals. The desired

Measurement signal of the absorption in the sample chamber A = -1Og (D ₂ ZD ₁ ) is determined by taking -1Og (I-SoZS ₁ ) = εcd-φ.

Here, ε is the extinction coefficient of ¹³ CO ₂ , c is the concentration and d is the beam path of the second partial beam 3b in the sample chamber 13. The constant parameter φ contains structural characteristics such as the division ratio of the beam splitter 9 and the ¹³ CO ₂ base concentration in the infrared spectrometer. The measurement signal thus provides directly the desired ¹³ CO ₂ concentration c of the sample at known (and constant) quantities ε, d and φ. During installation and maintenance, a calibration of the infrared spectrometer with known ¹³ CO ₂ concentrations are easily carried out. The absorption data is correlated with the gas flow meter 16, so that an adaptation to the concentration differences of the sample in the sample chamber 13 can be performed.

This way of data acquisition allows exploiting the high sensitivity of the first and second detectors 12 and 20, the two lock-in amplifiers 21 and 22 and the analog-to-digital converter. The entire device structure of the infrared spectrometer with the sample chamber 13 and said electronic elements is compact, portable and insensitive to external influences. This additionally increases the range of application.

FIG. 3 shows schematically two courses of the ¹³ CO ₂ concentration in exhaled breath air applied over a period of a few seconds. Such courses can be determined by means of a device according to the invention, as shown in FIG.

While the ¹³ CO ₂ concentration in the air of an individual with a healthy liver after application of a ¹³ C-labeled in the liver of the individual to ¹³ CO ₂ metabolizable substance increases very rapidly after the application of the substance and then goes back to a low level (solid curve), the ¹³ CO ₂ concentration in the respiratory air of an individual with a diseased liver after administration of the substance reaches only very low values in order to approach a level comparable to or lower than that of the individual as time progresses with healthy liver is (dashed curve).

Depending on the nature and severity of the liver disease, different curves may result, which may sometimes be quite similar to those in a healthy liver. Only in the case of a measurement with a high time resolution-preferably in the sub-second range, as is possible by a device according to the invention-can the curves shown in FIG. 3 be determined with sufficient accuracy, as represented by the specification of exemplary measurement times A to F. If a comparable examination is carried out with a device in which due to poorer time resolution, for example, only at the measurement times C and F could be measured, one would obtain over the period 0 to C or C to F integrated results.

This would mean that a distinction between individuals with healthy and diseased liver could be performed only insufficiently. That would be special then the case, if instead of the linear course of both curves shown in the figure 3 from the measurement time E still level differences occur that could easily remain undetected at a built-in due to poorer time resolution measurement by mutual cancellation.

The use of a device according to the invention - for example, as shown in Figure 1 - will be explained in more detail below with reference to application examples.

Example 1 - Use as Breath Analyzer for Liver Function Determination

Although an application of a device according to the invention is not limited only to respiratory tests but can generally be used for the analysis of any gas mixtures, it is suitable for use in respiratory analysis.

Thus, with a device according to FIG. 1, the liver function of an individual can be determined quantitatively. Such a provision is very important in many areas of medicine. Chronic liver disease is widespread in Europe, with hepatitis C alone, 8.9 million people are infected. These patients are usually in permanent medical care as the disease progresses. In therapy and management of patients with chronic liver disease, a much better therapy control can be achieved by quantification of liver function. The assessment of liver function is decisive for the precipitation of suitable therapeutic decisions.

Liver resection is a common procedure in today's surgery. It is performed as segmental resection or hemihepatectomy along the anatomical boundaries.

Extensive interventions in the parenchymal organ have been made possible by the development of various surgical techniques. However, postoperative morbidity and mortality from liver failure due to lack of liver function capacity in pre-damaged or excess liver residual tissue remains a significant problem. Much of the surgical intervention, however, must be done in pre-damaged liver tissue, usually a cirrhotic liver.

It is therefore of great advantage to be able to determine the functional liver capacity of a patient even before liver partial resection in order to not expose patients who do not have sufficient functional reserves of their liver tissue to their high surgical risk or to supply them with other therapeutic procedures. In liver transplantation the assessment of liver function is of particular importance because here the organ function is estimated at short notice and a fast therapy decision has to be made. In addition, in many clinical situations it is difficult to assess whether there is a parenchymal dysfunction or whether other causes are responsible for the clinical symptoms of the patients. In summary, therefore, there is a significant need to offer a truly quantitative liver function test for broad use in medicine. With a breath test with, for example, ¹³ C-labeled methacetin, this is possible if it is possible to measure the expired ¹³ CO ₂ amount absolutely and precisely in the exhaled air per time interval. Previous trials could only achieve semiquantitative results through unfavorable administration (oral) and inadequate measurement methodology (Matsumoto, K., Suehiro, M., et al., (1987).) [ ¹³ C] methacetin breath test for evaluation of liver damage. "Dig. Dis., 32 (4): 344-8; Klatt, S., C. Taut, et al. (1997). "Evaluation of the ¹³ C-methacetin breath test for quantitative liver function testing." Z. gastroenterol. 35 (8): 609-14). With appropriate application (intravenous), new calculation and accurate absolute concentration measurement by means of a device according to the invention far-reaching progress in this area are possible.

Example 2 - Use as Respiratory Analyzer to Determine Additional Parameters

Another application of a device according to the invention is the measurement of gastric emptying time. In many gastrointestinal diseases is the

Gastric emptying time disturbed (gastroparesis). This can be the case for diabetic patients, for example

Gastropathy, dyspepsia and other diseases will be the case. To measure the

Gastric emptying time is a test meal with a ¹³ C-labeled test substance (eg

Octanoic acid) and also measured the abatement of ¹³ CO ₂ . Here, a continuous measurement by means of a device according to the invention also provides a significantly better accuracy in the analysis of the data.

Further applications include ¹³ CO ₂ measurements in the diagnosis of pancreatic diseases, in the diagnosis of Helicobacter pylori and in the diagnosis of enzyme deficiency states (lactase deficiency etc.) (Swart, GR and JW van den Berg (1998).) ¹³ C breath gastroenterological practice. "Scand. J. Gastroenterol. Suppl. 225: 13-8). LIST OF REFERENCE NUMBERS

1 radiation source

2 drivers of the radiation source

3 light beam

0 ₃ βrcjtpr Tpiktrahl 3a, first Te ⁱ lstrahl 3b second part beam

4 cylindrical lens

5 first lens

6 second lens

7 filters

8 choppers

9 beam splitters

10 deflecting mirrors

11 third lens

12 first detector

13 sample chamber

14 gas inlet

15 gas outlet

16 gas flow meter

17 computers

18 mirrors

19 fourth lens

20 second detector

21 first lock-in amplifier

22 second lock-in amplifier D ₁ signal of the first detector D ₂ signal of the second detector

5 ₁ first partial signal of the signal of the first detector

5 ₂ first partial signal of the signal of the second detector

5 ₃ second partial signal of the signal of the first detector

5 ₄ second partial signal of the signal of the second detector S ₀ difference signal

ST ₁ first voltage divider

ST ₂ second voltage divider

Claims

claims

1. An apparatus for spectroscopic analysis of a gas, comprising at least one radiation source, at least one detection device, at least one sample chamber and a system of optical elements, which is provided and arranged to at least a portion of the radiation emitted by the radiation source through the sample chamber to the detection device wherein the sample chamber serves for receiving a gaseous sample containing the gas to be analyzed, characterized in that the device is designed so that the sample can flow through the sample chamber (13) continuously, and means (16) are provided, determine the pressure and / or the volume and / or the concentration of the sample in the sample chamber (13).

2. A device for spectroscopic analysis of a gas according to claim 1, characterized in that the device is designed such that substantially only an absorption of a single isotope of the gas from the emitted radiation (3) excited and / or by the detection device (12; 20) is detected.

3. A device for the spectroscopic analysis of a gas according to claim 2, characterized in that the radiation source and / or at least one of the optical elements for isotope-selective excitation of the absorption of the gas are configured.

4. A device for the spectroscopic analysis of a gas according to claim 2, characterized in that the detection device and / or at least one of the optical elements for isotope-selective detection of the absorption of the gas are configured.

5. A device for spectroscopic analysis of a gas according to any one of the preceding claims, characterized in that the device is designed such that the spectroscopic analysis is time-resolved.

6. A device for spectroscopic analysis of a gas according to any one of the preceding claims, characterized in that the time resolution is greater than 1 second.

7. A device for the spectroscopic analysis of a gas according to any one of the preceding claims, characterized in that the time resolution is 0.2 to 0.4 seconds.

8. A device for the spectroscopic analysis of a gas according to any one of the preceding claims, characterized in that the of the radiation source (1) emitted radiation (3) has a wavelength in the infrared range, in particular in the mid-infrared range.

9. A device for spectroscopic analysis of a gas according to any one of the preceding claims, characterized in that the radiation source (1) is a quantum cascade laser.

10. An apparatus for spectroscopic analysis of a gas according to claim 9, characterized in that the quantum cascade laser emits infrared light from a wavenumber range of 2280 to 2230 cm ^"1 .

1 1. A device for the spectroscopic analysis of a gas according to any one of the preceding claims, characterized in that the

Detection device (12; 20) is a photovoltaic MCT detector.

12. A device for the spectroscopic analysis of a gas according to any one of the preceding claims, characterized in that the path which the in the sample chamber (13) directed radiation (3b) must cover to on the

Detection device (20), by an arrangement of mirrors (18) is greater by a multiple than the largest longitudinal extent of the sample chamber (13).

13. A device for the spectroscopic analysis of a gas according to claim 12, characterized in that the path that the in the sample chamber (13) directed

Radiation (3b) must travel to hit the detection device (20) is at least 1, 5 m.

14. An apparatus for spectroscopic analysis of a gas according to any one of the preceding claims, characterized in that the sample containing the gas to be analyzed is breathing air.

15. An apparatus for spectroscopic analysis of a gas according to any one of the preceding claims, characterized in that the gas to be analyzed ^{13 is} CO ₂ .

16. An apparatus for spectroscopic analysis of a gas according to any one of the preceding claims, characterized in that the device has a connection by means of which a hose can be connected to the device, wherein the tube for introducing the sample into the sample chamber (13).

17. A device for spectroscopic analysis of a gas according to any one of the preceding claims, characterized in that the sample chamber (13) comprises an outlet means (15) for dispensing at least a portion of the sample, which is designed such that there is only a substance transport from the sample chamber (13).

18. A method for spectroscopic analysis of a gas comprising the following steps:

Introducing a sample containing the gas to be analyzed in a sample chamber by the sample flows into the sample chamber, wherein the sample chamber, a subsequent outflow of the sample from the

Sample chamber allows,

Directing at least part of a radiation emitted by a radiation source through the sample chamber onto a detection device by means of a system of optical elements for analyzing the gas and - detecting absorption of the radiation by the gas to be analyzed by means of the detection device, characterized in that a change in the pressure and / or the volume and / or concentration of the sample in the sample chamber (13) during analysis is determined by suitable means (16).

19. A method for the spectroscopic analysis of a gas according to claim 18, characterized in that substantially only an absorption of a single isotope of the gas from the emitted radiation (3) is excited and detected by the detection device (12;

20. A method for the spectroscopic analysis of a gas according to claim 18 or 19, characterized in that the spectroscopic analysis is time-resolved.

21. A method for spectroscopic analysis of a gas according to any one of claims 18 to 20, characterized in that the time resolution is greater than 1 second.

22. A method for the spectroscopic analysis of a gas according to any one of claims 18 to 21, characterized in that the time resolution is 0.2 to 0.4 seconds.

23. A method for spectroscopic analysis of a gas according to any one of claims 18 to 22, characterized in that an absorption of the gas to be analyzed in the middle infrared range is detected.

24. A method for the spectroscopic analysis of a gas according to any one of claims 18 to 23, characterized in that the sample containing the gas to be analyzed is respiratory air.

25. A method for the spectroscopic analysis of a gas according to any one of claims 18 to 24, characterized in that the gas to be analyzed ^{13 is} CO ₂ .

26. A method for the spectroscopic analysis of a gas according to any one of claims 18 to 25, characterized in that the introduction of the sample into the sample chamber (13) by means of a hose.

27. A method for the spectroscopic analysis of a gas according to any one of claims 18 to 26, characterized in that the application of the sample by an outlet means (15) takes place, which allows only a substance transport out of the sample chamber (13) out.

28. Use of a device according to one of claims 1 to 17 for the determination of a biological parameter of an individual by means of a spectroscopic analysis of a gaseous sample originating from the individual.

29. Use according to claim 28, characterized in that the biological

Parameter is the function of an organ of the individual.

Use of a device according to claim 28, characterized in that the biological parameter is the concentration of an enzyme in an organ and / or tissue of the individual.

Use of a device according to claim 28, characterized in that the biological parameter is the concentration of at least one microbial species in an organ and / or tissue of the individual.