EP1217643B1 - Méthode et dispositif pour la détermination de l' état d'organismes et de produits naturels ainsi que pour l'analyse de mélanges gazeux comprenant des composantes principales et secondaires - Google Patents

Méthode et dispositif pour la détermination de l' état d'organismes et de produits naturels ainsi que pour l'analyse de mélanges gazeux comprenant des composantes principales et secondaires Download PDF

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EP1217643B1
EP1217643B1 EP00127558A EP00127558A EP1217643B1 EP 1217643 B1 EP1217643 B1 EP 1217643B1 EP 00127558 A EP00127558 A EP 00127558A EP 00127558 A EP00127558 A EP 00127558A EP 1217643 B1 EP1217643 B1 EP 1217643B1
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EP
European Patent Office
Prior art keywords
gaseous mixture
sample
components
ion beam
mass spectrometer
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EP00127558A
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German (de)
English (en)
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EP1217643A1 (fr
Inventor
Johannes Dr. Villinger
Werner Dr. Federer
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V & F Analyse- und Messtechnik GmbH
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V & F Analyse- und Messtechnik GmbH
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Priority to DE50015353T priority Critical patent/DE50015353D1/de
Application filed by V & F Analyse- und Messtechnik GmbH filed Critical V & F Analyse- und Messtechnik GmbH
Priority to DK00127558T priority patent/DK1217643T3/da
Priority to AT00127558T priority patent/ATE408237T1/de
Priority to EP00127558A priority patent/EP1217643B1/fr
Priority to EP01986885A priority patent/EP1342254A2/fr
Priority to US10/433,370 priority patent/US6982416B2/en
Priority to KR1020037007736A priority patent/KR100885654B1/ko
Priority to JP2002558304A priority patent/JP4316883B2/ja
Priority to CNB018205844A priority patent/CN100481309C/zh
Priority to PCT/EP2001/014804 priority patent/WO2002058106A2/fr
Publication of EP1217643A1 publication Critical patent/EP1217643A1/fr
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    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00—Particle spectrometers or separator tubes
    • H01J49/02—Details
    • H01J49/04—Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locks; Arrangements for external adjustment of electron- or ion-optical components
    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00—Particle spectrometers or separator tubes
    • H01J49/02—Details
    • H01J49/10—Ion sources; Ion guns
    • H01J49/14—Ion sources; Ion guns using particle bombardment, e.g. ionisation chambers
    • H01J49/145—Ion sources; Ion guns using particle bombardment, e.g. ionisation chambers using chemical ionisation

Definitions

  • the present invention relates to a method for assessing the state of organisms and natural products which release substances into the surrounding atmosphere, in which one or more of these substances are determined in a gaseous mixture, a method of analyzing a gaseous mixture with main and minor components , as well as an apparatus for carrying out these methods comprising a mass spectrometer.
  • WO 00/74553 describes a device for checking the calibration of a gas analyzer, especially for use with breath samples.
  • US 5,032,722 describes a time-of-flight mass spectrometer that allows additional mass selection and / or a secondary ionization step.
  • the object of the present invention is to provide a method for the analysis of gaseous mixtures, which allows the rapid determination of major and minor components of the gaseous mixture.
  • Another object of the invention is to provide an apparatus for the analysis of gaseous mixtures which is suitable for carrying out the above-mentioned methods and permits rapid analysis of samples of gaseous mixtures whose components are present in a wide concentration range.
  • the invention is based on the finding that the abovementioned objects can be achieved with the aid of a mass spectrometer in which an ion beam acts on the sample of the gaseous mixture to be analyzed in a high vacuum.
  • the present invention therefore provides a first method for assessing the state of organisms and natural products which release substances into the surrounding atmosphere, in which two or more of these substances are determined to be components of a gaseous mixture, wherein the gaseous mixture to be analyzed consists of main components and secondary components, and the concentrations of the secondary components are less than those of the main components by at least a factor of 10, wherein in each case the concentration of at least one main component and at least one minor component of the gaseous mixture is determined by means of a mass spectrometer, and in which acts on the sample of the gaseous mixture, an ion beam in a high vacuum, and the values obtained in the determination are evaluated to determine the state.
  • natural products are natural products such as fruit, vegetables, meat, cow's milk, etc., products obtained by natural production processes, such as e.g. Wine, beer, cheese, edible oil, etc., as well as products obtained by refining natural products, e.g. Coffee beans, smoked ham, etc. understood.
  • gaseous mixtures are mixtures of substances which, in addition to main components gaseous at room temperature, contain further components which are located in the gas phase formed by the main components.
  • the method according to the invention has the advantage that no samples have to be taken by artificial means from the organism or natural product to be examined, whereby any injury to the organism or natural product is avoided. It is therefore a non-invasive procedure.
  • Another advantage of the method is that the method of analyzing a sample takes only a short time in the range of a few minutes.
  • the method offers the advantage that, when determining several components of the gaseous mixture to be analyzed, substantially no interference is obtained in the determination of the components which prevent an analysis of individual specific components.
  • the method is used to assess the condition of humans and animals.
  • This has the advantage that from the object to be examined no samples such as blood samples must be taken, especially for carrying, because such sampling must be performed by trained personnel, in the case of humans, for example, by doctors.
  • such a sampling of humans and animals is perceived as unpleasant.
  • the method according to the invention offers the advantage that, on the one hand, sampling is not perceived as unpleasant and, on the other hand, it can also be carried out by untrained personnel or by the subject himself.
  • the exhaled air of humans is used in the process according to the invention as gaseous mixture.
  • the sampling can be done very simply and, on the other hand, the substances obtained in the exhaled air make it possible to assess the condition of the subject with regard to a large number of clinical pictures and metabolic processes.
  • the concentration of two or more of the substances contained in the gaseous mixture is determined quantitatively. Since the method according to the invention comprises the determination by means of a mass spectrometer in which an ion beam is applied to the sample of the gaseous mixture in a high vacuum, the quantities of the determined substances are linearly proportional to the detected signal, therefore the quantitative detection can be carried out in a simple manner.
  • the quantitative determination offers the advantage that it can be used to make further statements on the condition of the organism or natural product. In particular, in multiple measurements in time sequence changes in the concentrations of substances and thus changes in the state of the organism or natural product can be detected.
  • the sample of the gaseous mixture without pretreatment is supplied to the mass spectrometer. This offers the advantages of minimizing the time required to measure a sample and of not incurring any additional costs associated with pretreatment steps such as concentration of the sample.
  • the gaseous mixture to be analyzed consists of main components and secondary components, the concentrations of the secondary components being lower than those of the main components by at least a factor of 10, preferably 50, more preferably 100.
  • the gaseous mixture to be analyzed consists in each case of at least one main component in the concentration range of ⁇ 0.1% by volume, preferably ⁇ 1% by volume, and at least one minor component in the concentration range of ⁇ 0.1% by volume, preferably ⁇ 0.03 vol%, the concentration being determined by at least one of the major and minor components.
  • the concentration of at least one of the major and minor components is quantified.
  • the concentration of at least one of the major and a plurality of minor components is determined quantitatively.
  • the major components of the gaseous mixture to be analyzed are substantially the same as those of the atmospheric air. More preferably, the concentrations are also the major components of the gaseous mixture to be analyzed substantially equal to those of the atmospheric air.
  • all the components which are used in the detection in the mass spectrometer has a molecular mass of up to 500, preferably a molecular mass of up to 200, detected quantitatively.
  • the ion beam which acts on the sample molecules in a high vacuum, comprises an atomic ion beam.
  • the ion beam includes ions that are in the electronic ground state and / or in a selectively excited metastable state.
  • the ion beam which acts on the sample molecules in a high vacuum, comprises at least two ion beams with different ionization potential.
  • the ion beam which acts on the sample molecules in a high vacuum, comprises a Hg ion beam.
  • the ion beam which acts on the sample molecules in a high vacuum, comprises an Hg ion beam and additionally a Kr ion beam and / or an Xe ion beam.
  • the various ion beams act successively on the sample molecules in a high vacuum.
  • substances with an ionization potential ⁇ 17 eV are determined.
  • only substances are determined by the method according to the invention, which have a vapor pressure of at least 10 -3 mbar at room temperature.
  • the evaluation of the values obtained is carried out so that the concentration of the secondary components is based on the concentration of at least one of the main components.
  • the present invention further provides a second method of analyzing a gaseous mixture according to claim 2.
  • This method has the advantage that it allows a fast and simultaneous determination of major and minor components of a gas mixture and therefore allows comprehensive statements about the gas mixture.
  • a correlation between at least one main component and at least one secondary component is produced for the evaluation of the data obtained by the mass spectrometer.
  • This offers, for example, the advantage that the evaluation of the data can be carried out by normalizing the data of the secondary components to that of the main components. Furthermore, it can be closed, for example, by the proportion of major components on faulty samples and these are discarded.
  • the present invention further provides a gaseous mixture analysis apparatus comprising a mass spectrometer having a gas introduction system, wherein a molecular beam is generated in an intermediate vacuum from the gaseous mixture sample to be analyzed which is then generated by means of a pressure gradient in a capillary, a second molecular beam in a high vacuum, which is ionized by an ion beam, wherein the pressure of the intermediate vacuum is kept constant.
  • the device according to the invention has the advantage that the second molecular beam arriving in the high-vacuum analyzer of the mass spectrometer has a constant particle density. In this way, the viscosity of the second sample molecular beam is kept constant. Furthermore, a high density of the second sample molecular beam is achieved with the device, wherein simultaneously prevail at the impact of the ion beam on the sample molecular beam single impact conditions.
  • the sensitivity of the mass spectrometer can be increased up to the ppb range and at the same time components of gaseous mixtures in the volume percent range can be determined.
  • the gas introduction system of the device according to the invention is inert to the components contained in the sample of the gaseous mixture, so that no flushing of the system must take place before the measurement of a new sample.
  • the ion beam which acts on the sample molecules in a high vacuum, comprises at least two ion beams with different ionization potential.
  • the ion beam which acts on the sample molecules in a high vacuum, comprises an atomic ion beam.
  • the ion beam includes ions that are in the electronic ground state and / or in a selectively excited metastable state.
  • the ion beam which acts on the sample molecules in a high vacuum, comprises an Hg ion beam.
  • the ion beam which acts on the sample molecules in a high vacuum, comprises an Hg ion beam and additionally a Kr ion beam and / or an Xe ion beam.
  • the various ion beams act successively on the sample molecules in a high vacuum.
  • the methods according to the invention preferably comprise the use of the device according to the invention.
  • an increased content of methane in the air can be caused by the incorrect colonization of the small intestine with colon bacteria, which then produce methane in the small intestine, which passes through the bloodstream into the lungs and thus into the exhaled air.
  • increased methane levels may also occur in certain types of malnutrition.
  • the propanol content in relation to the ethanol content in the exhaled air is increased by a factor of about 10.
  • the pentane level in the exhaled air is a measure of changes in lipid activity in the body and related diseases. For example, elevated levels of pentane are detected in rheumatic inflammation, lung injury caused by inhalation of high concentrations of oxygen, heart attack patients and patients with cancer of the respiratory organs.
  • the pentane content in the exhaled air may also be elevated in schizophrenia and multiple sclerosis.
  • a linear relationship has been found between the age of subjects and the pentane content in their exhaled air.
  • Bacterial strains causing inflammatory sites cause an increased level of NO in the exhaled air.
  • ketones in the exhaled air is detected when the fatty acid supply in the body is high due to increased lipolysis. This can be attributed to various causes such as hunger or insulin mails (diabetes mellitus).
  • ketonuria an increased concentration of ketone bodies (acetoacetate, R3 hydroxybutyrate and acetone) is also found. This is due to the low glycogen content of the liver as a result of carbohydrate metabolism failure.
  • ketoacidosis such as in coma diabeticum, starvation or alcoholism, an increased content of propionic acid and butyric acid in the exhaled air can be detected.
  • an increased content of, for example, phenols in the exhaled air can be determined.
  • the metabolic products of bacteria found in the human body such as CO 2 and H 2 (Escherichia coli) or H 2 S (Proteus) can be found in the exhaled air. Especially in the case of infection by clostridia (gas gangrene bacteria), volatile fatty acids can be detected.
  • the inventive method can be used, for example, to control pilots, train or bus drivers before driving the respective means of transport.
  • the composition of the exhaled air is also changed compared to non-doped athletes.
  • athletes can be checked for the intake of doping before the competitions.
  • the method according to the invention can therefore be used for the diagnosis of clinical pictures and metabolic disorders in the human body of all kinds.
  • a monitoring of the metabolism of organisms when ingesting pharmaceuticals the monitoring of therapeutic measures such. the continuous control of healing processes as well as the monitoring of provocation tests in which a substance is given in a certain (high) dose and the body's reaction to that substance is monitored.
  • the inventive method is not limited to the analysis of the exhaled air of humans, but it can also, for example, samples of human gaseous mixtures of other nature such as the exhalations and the sweat, as well as the gas phases of urine, blood, faeces and other body fluids done.
  • the sampling can be carried out, for example, by picking it up by means of a cotton swab and analyzing the gas phase over the cotton swab.
  • inventive method for quality control of natural products of all kinds can be used, where, for example, when certain gaseous substances in the gas phase over the natural product on a decomposition of the product can be concluded.
  • certain gaseous substances in the gas phase over the natural product on a decomposition of the product can be concluded.
  • certain gaseous substances in the gas phase over the natural product on a decomposition of the product can be concluded.
  • in the analysis of the gas phase over fresh meat first lactic acid is detected, with increasing age then increasingly NH 3 and finally S compounds.
  • Another conceivable application of the method according to the invention is the detection of BSE-sick animals, for example via the altered composition of their exhaled air.
  • FIG. 1 shows the device according to the invention in a schematic drawing.
  • FIG. 2 shows a graphical representation of the results of the measurements of the example.
  • the sampling and the sample supply to the mass spectrometer can on the one hand take place so that a direct connection between the gas space in which the gas mixture to be analyzed and the mass spectrometer is produced.
  • this can be done with the aid of a breathing mask, such as in WO 99/20177 is described.
  • This method can be used for example in emergency medicine, for example for the detection of rapidly deteriorating health conditions.
  • Another application of the online method may be the real-time monitoring of metabolic processes, for example after a provocative test.
  • the sampling can also be done so that the subject and mass spectrometers are separated in time and / or space, so that the exhaled air sample must first be stored in a suitable vessel.
  • a suitable vessel preferably glass vials are used with a preferred volume of 20 ml.
  • vials have the advantages of being very cost effective, making them suitable for single use. Furthermore, they have excellent inertness compared to other gas storage systems and they are very easy to handle with the help of an autosampler.
  • the sample is taken so that the test person exhales evenly (preferably through the nose) and through a common drinking straw about 1 to 2 cm above the bottom of the vessel into the vial.
  • the vial is then sealed airtight. This is preferably done with a crimp cap, which is crimped after sampling with the Glasvial. It was found that a time of a few seconds, in which the vial is still uncapped after exhalation of the subject, have no adverse effects, such as a change in composition, on the gaseous mixture exhaled by the subject.
  • the crimp cap is preferably formed so that it is completely covered with Teflon in the area where direct contact of the cap with the interior of the vessel, that is, with the exhaled gaseous mixture takes place.
  • the opening of the glass vial is advantageously designed so that its upper edge has a conically sloping outward shape.
  • the crimp cap can be formed so that it comprises an outer ring of butyl rubber, which conforms elastically to the conical outer wall of the vial and thus acts sealingly. This preferred embodiment of the glass vial seal ensures maximum inertia over the gaseous mixture exhaled by the subject.
  • a second vial which has not come into contact with the test subject's breathing air is connected in parallel to the glass vial filled with exhaled breath of the test subject. closed in the vicinity of the subject (Verticianvial).
  • the exhaled air of the subject can be stored for several days without loss of quality. This can be used, for example, to transport the samples from the attending physician to the evaluation laboratory. This type of sampling is also referred to as offline. The sampling shows the advantage that it can be carried out by untrained personnel due to their simplicity.
  • sampling can also be done offline or online. For example, in offline sampling, a glass vial that has been in contact with the gas phase immediately above the product to be examined for some time may be closed.
  • the samples are first mounted on an autosampler, for example.
  • an autosampler for example.
  • This can be, for example, a modified CNC machine of the type "step-4 milling basic 540", which has been modified so that it fully automatically samples 70 samples consisting of 70 sample and comparison vials.
  • the sample is preferably heated to a temperature higher than room temperature, more preferably 65 ° C, before being fed to the mass spectrometer.
  • the gas passes through a hot capillary, which has a higher temperature than the autosampler, to the gas introduction system, which in turn has a higher temperature than the capillary.
  • the amount of gas passing through the capillary is at most about 5 ml / min.
  • the gas introduction system of the mass spectrometer is designed to compensate for pressure and viscosity fluctuations, so that the same particle density is always injected into the analyzer of the mass spectrometer.
  • mass spectrometers are used in which an ion beam acts on the sample molecules in a high vacuum. This type of mass spectrometer is used to obtain quantitative concentration values No calibration required for the individual detected masses. So there is a direct absolute indication of the concentrations.
  • the mass spectrometer according to the invention further allows a linear detection of the concentrations of the masses in the concentration range of 10 -7 vol% (ppb) up to 10 2 % by volume, ie in an amount of 10 9 . This means that the quantities of the given masses are obtained directly from the measurement.
  • the components of the gaseous mixture are detected in the mass spectrometer according to their molecular mass.
  • the sample gas is introduced into a high-vacuum chamber and converted into ions, which are subsequently selected according to their mass by electromagnetic fields and counted in a particle counter.
  • the action of an ion beam on the molecular beam of the sample of the gaseous mixture in a high vacuum preferably comprises a Hg ion beam.
  • the Hg ion beam has an ionization energy of 10.4 eV, which is sufficient for the ionization of over 90% of the compounds to be determined.
  • the main components of the exhaled air such as N 2 and O 2 are not ionized, but selectively only the secondary components contained in the exhaled air, which are thus detected exclusively. This allows a quantitative determination of components that are present only in traces up to 10 -7 vol%. Furthermore, very few compounds are fragmented by the Hg ion beam.
  • the mass spectrometer use different ionization levels, that is, at least two primary ion beams, to move between molecules of identical mass to be able to distinguish. This distinction is based on the principle that each molecule has an individual ionization energy at which the molecule is transformed into an ion.
  • an Hg ion beam is used together with a krypton ion beam and / or a xenon ion beam.
  • the sequence of the different ion beams in the measurement can be done in any order.
  • the molecules N 2 and CO having identical mass can be discriminated because of their different ionization potentials of 14.2 eV (N 2 ) and 13.7 eV (CO) become.
  • methanol and O 2 are distinguished by ionization with a xenon ion beam (12.2 eV), which forms an O 2 + ion with mass 32 and a CH 3 O + ion with mass 31.
  • a xenon ion beam (12.2 eV)
  • Higher hydrocarbons for example, require ionization energies in the range of 10 eV, as generated by a mercury ion beam with an energy of 10.4 eV.
  • the measurement of the samples of the gaseous mixtures is carried out so that the concentrations of all the masses up to a molecular weight after the ionization of 500, preferably 200, are determined quantitatively.
  • the compounds carbon dioxide, carbon monoxide, water, ethanol, isoprene, methane, acetone, ammonia, formic acid, acetic acid, acetaldehyde, acetylene, acetonitrile, benzene, methylamine, formaldehyde, hydrogen sulfide, nitrous acid, methanol, oxygen, propanol, Toluene, methyl, ethyl group, nitric oxide, protonated water as water adduct, acetyl group, formyl group, formaldehyde * protonated water, pyridine, pentane, cyclopentane, methyl ethyl ketone, propionic acid, butyric acid, methylmercaptan, ethylene, dinitrogen monoxide, propane and sulfur dioxide.
  • the inventive method further offers the advantage that chemical compounds of all kinds, ie. For example, acids and bases, polar and nonpolar substances, can be measured simultaneously with a measurement.
  • the CO 2 content of the sample is determined. At a take-off temperature of the test gas mixture from the vial of 65 ° normally results in a CO 2 content of about 2 to 3.5 vol%. It has been found that this CO 2 value varies only in the range of about 10% in normal exhalation samples. Therefore, if the measured CO 2 content significantly outside this normal range, it can be assumed that either the Probenvial was improperly closed or improperly handled or the subject has used a wrong breathing technique, so that the exhaled air of the lungs was not detected. By means of this and analogous criteria, adulterated samples can be discarded.
  • the measuring procedure is repeated at least five times for one sample or comparison vial (5 cycles) and the average values are formed from these cycles.
  • One cycle takes about one minute to measure 200 masses.
  • the sample vial and then the comparison vial are determined.
  • the mean values are formed from the results of the measuring cycles.
  • the sample may either be discarded or the amount of contaminant component in the exhaled air sample may be obtained from the difference (trial vial minus control vial). This approach makes it possible to eliminate any contamination in the vials, as the difference of equal contamination results in zero and results consisting of respiratory air and contaminants correspond to the actual exhaled value.
  • contamination components of the ambient air may also be absorbed by the lungs and therefore have a lower concentration in the exhaled air than in the ambient air.
  • contaminations i.a. when a certain concentration in the ambient air is exceeded, they can no longer be absorbed.
  • a breakthrough curve is obtained by measuring the exhaled air as a function of the concentration of the contamination.
  • the evaluation of the data is carried out in such a way that the measured quantitative values for the components, which are determined either by their mass or also by their chemical nature, are compared with the normal values of the respective component.
  • the measured quantitative values for the components which are determined either by their mass or also by their chemical nature, are compared with the normal values of the respective component.
  • the normal values can be obtained, for example, by series measurements on a large number of subjects for determining the normal state of the human respiratory air.
  • the normal values can also be taken from the literature, as far as they are known.
  • the normal values generally include a certain range.
  • the quantitative values measured for the components are normalized to the value of one of the main components of the gaseous mixture, preferably CO 2 . Normalization achieves a relationship between the content of the individual components and the actual exhaled amount of respiratory air per subject. This has the advantage of having values between different subjects and values obtained by staggered measurements of a subject's breathing air can be compared.
  • the value determined after the normalization is divided by the maximum value known for human subjects. This results in values for the individual components ranging from 0 to 1. This further simplifies the evaluation and makes it easier to understand for the evaluating specialist personnel (doctors).
  • correlations are made between the measured values of individual components in order to detect certain clinical pictures.
  • the ethanol / propanal ratio can be determined to provide information about a possible Hepatitis infection.
  • a particular advantage of the method in determining all components in a certain mass range is that an overall view of a variety of clinical pictures and metabolic processes is obtained.
  • both the pentane content and the content of H 2 S and CS 2 in the exhaled air increase, so that with simultaneous determination of these components other clinical pictures can be ruled out in which only the content of one of these components increases is.
  • the observable metabolic processes can be both structural processes (anabolisms) and degradation processes (catabolisms).
  • the inventive method also has the advantage that it can also be performed by untrained personnel, resulting in a cost savings.
  • the evaluation of the measurements is advantageously carried out computerized.
  • An embodiment of the device according to the invention comprises a gas inlet system with a flexible gas transfer capillary (3), which preferably consists of fused silica, has an inner diameter of 250 microns and in a quarter inch Teflon tube is placed.
  • the teflon hose also contains a heating wire.
  • the capillary (3) is connected to cannula (2) for sampling from a Probenvial (1).
  • the various components up to the pinhole (5) in each case have higher temperature in the direction of the gas flow.
  • the sample vial (1) is preferably heated to 65 ° C., the cannula (2) to 85 ° C. and the gas transfer capillary (3) to 100 ° C.
  • the small diameter of the capillary also allows that smallest amounts of gas can be removed from the sample vial.
  • a gradient vacuum is created in this way, which, depending on the vapor pressure of the individual component, causes a selective increase in concentration and thus better detection limits.
  • the gas inlet system has the advantage that it is inert to the gaseous mixtures to be analyzed and thus has no memory effects. Therefore, rinsing the system is not necessary to analyze a new sample.
  • the gas flow through the capillary (3) is limited to at most 5 ml / min.
  • a pressure of about 700 mbar In the area in front of the pinhole there is a pressure of about 700 mbar, if atmospheric pressure prevailed in the sample vial before sampling.
  • the cannula (2) is controlled by a robot to the desired sample vial.
  • Gasschaltventile (4) can be added via the zero gas and calibration gases, preferably up to a pressure of at most 1.5 bar. However, the total gas flow must be greater than the back diffusion.
  • the Pump (9) which is preferably a two-stage, oil-free vacuum pump with 0.2 to 200 mbar autogenous pressure, a pressure of about 20 mbar generated.
  • the pressure of about 20 mbar is kept at a constant value by a proportional control valve (8), which can allow auxiliary air or inert gases to flow into this space.
  • the control of the proportional control valve (8) is preferably carried out via a capacitive absolute pressure sensor (7), which measures the pressure within the intermediate vacuum chamber (24) accurately and independently of the composition of the gas. This ensures that pressure fluctuations of the sample molecular beam (6), as occur for example in the repeated measurement from the same Probenvial, can be compensated and no changes in the viscosity of the sample molecular flow in the capillary (10) occur. Thus, a sample molecule flow of constant particle density enters into the further capillary (10).
  • the capillary (10) In the intermediate vacuum chamber (24) is located in the region of the molecular beam (6) one end of the capillary (10), which has a preferred inner diameter of 250 microns and to a temperature above 100 ° C, preferably 220 ° C, heated. The heating of the capillary (10) causes the desorption times are kept as low as possible.
  • the gas jet pressure upstream of the capillary (10) is always exactly the same. This arrangement enables quantitative determination of components down to the 10 -7 vol% range.
  • the other end of the capillary (10) is located in the high vacuum chamber (22), in which, for example, a turbomolecular pump (23) a high vacuum, preferably of at least 10 -7 mbar is generated.
  • the capillary end is just in front of an open slot of the octopole guide field (16) in the charge exchange chamber (17).
  • the sample molecular beam (6) passes through the capillary (10) into the charge exchange region (17) of the high-vacuum chamber (22), at the end of the capillary (10) forming a second molecular beam (10). 11).
  • the primary ion beam (12) for the ionization of the molecular beam (11) is formed so that gas is taken from one of the gas reservoirs (13) of mercury, krypton and xenon reduced pressure and the electron impact source (14) comprising hot tungsten filament, anode and Ziehblende out becomes.
  • the resulting primary ion beam (12) is passed through a first octopole guide field (15). Only high molecular weights (primary ions) are guided and the masses of impurities in the gas reservoirs (13) suppressed in order to achieve a high signal-to-noise ratio for the substances to be measured.
  • the primary ion beam (12) is then passed on in a second octopole guide field (16), which has the same transmission for all types of molecules.
  • a sample molecule ion beam (18) is generated in single impact processes at a pressure of on average 10 -4 mbar, the sample molecules are then separated in the quadrupole analyzer (19) according to their mass / charge ratio.
  • the sample molecule ions are then converted in the ion detector (20) to electronically processable electron pulses.
  • the electron pulses are then decoupled (21) for the counting electronics.
  • Octopole arrangements for ion beam based ion mass spectrometers are, for example, in EP 0 290 712 and De 196 28 093 described.
  • exhaled air analyzes were carried out by nine subjects in a clinical test. For this purpose, samples of the exhaled air of each subject were taken so that the subject inhaled and exhaled evenly over the nose a few breaths, then the air for two to three seconds and then stopped the air evenly through a straw, the end of one to two centimeters above the floor of a glass vial with a volume of 20 cm 3 , exhaled.
  • sample vial was closed in each case with a crimp cap by means of a crimping pliers. This occlusion occurred no later than about five seconds after the subject had exhaled into the vial.
  • Sample and reference vials were each placed in an autosampler and pre-thermostated there for at least 10 minutes at 65 ° C.
  • the sample and then the reference vial of the subjects were determined by means of the above-described embodiment of the device according to the invention.
  • the measurement of each vial took place in at least six cycles, ie the content of each vial was determined at least six times.
  • the mean value was then formed from the at least six values obtained for the respective mass.
  • the mean value obtained for the respective comparison vial was then subtracted from the mean value obtained for the sample vial for the respective mass.
  • the normalization of the mean values to the value of CO 2 was then carried out by dividing the mean values by the value obtained for CO 2 .
  • the normalized values were then divided by the maximum value for that mass known for the particular mass from a series measurement on a plurality of subjects. Values between 0 and 1 were obtained for each mass.
  • FIG. 2 The results of the measurements on the nine volunteers are shown graphically.
  • the values of the detected masses are shown in the range from 0 to 102 according to the following code: Black: Value range 0.75 - 1 Dark gray: Value range 0.5 - 0.75 Light gray: Value range 0.25 - 0.5 White: Value range 0 - 0.25
  • FIG. 2 It can be seen that the values for subject 9 differ significantly from the values of the other subjects.
  • the subject 9 had a not clearly defined disease, it was assumed that a septic disease, ie a bacterial infection with the result of liver and Coagulation disorder was present.
  • a septic disease ie a bacterial infection with the result of liver and Coagulation disorder was present.
  • subject 9 suffered brain death and subsequently the definitive death.
  • This example shows that the condition of a subject with a severe health disorder can be determined over that of other subjects.

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  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Engineering & Computer Science (AREA)
  • Plasma & Fusion (AREA)
  • Other Investigation Or Analysis Of Materials By Electrical Means (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Electron Tubes For Measurement (AREA)
  • Investigating Or Analysing Materials By The Use Of Chemical Reactions (AREA)
  • Investigating Or Analyzing Non-Biological Materials By The Use Of Chemical Means (AREA)
  • Measurement Of The Respiration, Hearing Ability, Form, And Blood Characteristics Of Living Organisms (AREA)
  • Investigating Or Analyzing Materials By The Use Of Fluid Adsorption Or Reactions (AREA)
  • Sampling And Sample Adjustment (AREA)

Claims (7)

  1. Procédé d'évaluation de l'état d'organismes et de produits naturels qui délivrent des substances dans l'atmosphère qui les entoure,
    dans lequel au moins deux de ces substances sont déterminées dans un mélange gazeux,
    dans lequel le mélange gazeux à analyser est constitué de composants principaux et de composants secondaires et les concentrations des composants secondaires se situent en-dessous de celles des composants principaux au moins du facteur 10,
    dans lequel on détermine, respectivement, la concentration d'au moins un composant principal et d'au moins un composant secondaire du mélange gazeux à l'aide d'un spectromètre de masse, et
    les valeurs obtenues lors de la détermination sont ensuite exploitées pour évaluer l'état,
    caractérisé en ce que
    un faisceau ionique agit sous vide poussé sur un échantillon du mélange gazeux.
  2. Procédé d'évaluation de l'état d'organismes et de produits naturels qui délivrent des substances dans l'atmosphère qui les entoure,
    dans lequel au moins une de ces substances est déterminée dans un mélange gazeux,
    dans lequel la détermination se fait à l'aide d'un spectromètre de masse doté d'un système d'introduction de gaz, et les valeurs obtenues lors de la détermination sont exploitées pour évaluer l'état,
    caractérisé en ce que,
    dans le système d'introduction de gaz, à partir d'un échantillon du mélange gazeux à analyser, on produit sous un vide intermédiaire (24) un faisceau moléculaire (6), à partir duquel est ensuite produit sous vide poussé (22), à l'aide d'un gradient de pression, dans un tube capillaire (10) un second faisceau moléculaire (11), qui est ionisé par un faisceau ionique (12), la pression du vide intermédiaire (24) étant maintenue constante.
  3. Procédé selon l'une quelconque des revendications précédentes, dans lequel les organismes sont des hommes ou des animaux.
  4. Procédé selon l'une quelconque des revendications précédentes, dans lequel le mélange gazeux est l'air rejeté par l'homme.
  5. Procédé selon l'une quelconque des revendications précédentes, dans lequel on détermine quantitativement la concentration d'une ou plusieurs des substances.
  6. Procédé selon l'une quelconque des revendications précédentes, dans lequel on détermine, respectivement, au moins un composant principal dans la plage de concentrations ≥ 1 % en volume et au moins un composant secondaire dans la plage de concentrations ≤ 0,03 % en volume.
  7. Dispositif d'analyse d'un mélange gazeux qui comprend un spectromètre de masse doté d'un système d'introduction de gaz, dans lequel est produit, à partir de l'échantillon du mélange gazeux à analyser un faisceau moléculaire (6), sous un vide intermédiaire (24), dans lequel la pression du vide intermédiaire (24) est maintenue constante et à partir de celle-ci est ensuite produit à l'aide d'un gradient de pression dans un tube capillaire (10) un second faisceau moléculaire (11) sous vide poussé (22),
    caractérisé en ce que le second faisceau moléculaire (11) est ionisé par un faisceau ionique (12).
EP00127558A 2000-12-15 2000-12-15 Méthode et dispositif pour la détermination de l' état d'organismes et de produits naturels ainsi que pour l'analyse de mélanges gazeux comprenant des composantes principales et secondaires Expired - Lifetime EP1217643B1 (fr)

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DK00127558T DK1217643T3 (da) 2000-12-15 2000-12-15 Fremgangsmåde og indretning til vurdering af tilstanden i organismer og naturprodukter samt til analyse af en gasformig blanding med hoved- og bikomponenter
AT00127558T ATE408237T1 (de) 2000-12-15 2000-12-15 Verfahren und vorrichtung zur beurteilung des zustandes von organismen und naturprodukten sowie zur analyse einer gasförmigen mischung mit haupt- und nebenkomponenten
EP00127558A EP1217643B1 (fr) 2000-12-15 2000-12-15 Méthode et dispositif pour la détermination de l' état d'organismes et de produits naturels ainsi que pour l'analyse de mélanges gazeux comprenant des composantes principales et secondaires
DE50015353T DE50015353D1 (de) 2000-12-15 2000-12-15 Verfahren und Vorrichtung zur Beurteilung des Zustandes von Organismen und Naturprodukten sowie zur Analyse einer gasförmigen Mischung mit Haupt- und Nebenkomponenten
US10/433,370 US6982416B2 (en) 2000-12-15 2001-12-14 Method and device for evaluating the state of organisms and natural products and for analyzing a gaseous mixture comprising main constituents and secondary constituents
KR1020037007736A KR100885654B1 (ko) 2000-12-15 2001-12-14 유기체 및 천연물의 상태를 평가하고, 주성분 및 제 2성분을 함유하는 기체 혼합물을 분석하기 위한 방법 및 장치
EP01986885A EP1342254A2 (fr) 2000-12-15 2001-12-14 Procede et dispositif pour evaluer l'etat d'organismes et de produits naturels et pour analyser un melange gazeux comprenant des composants principaux et des composants secondaires
JP2002558304A JP4316883B2 (ja) 2000-12-15 2001-12-14 生物体及び天然物の状態を評価するための、また主成分と副成分を含む混合気体を分析するための方法及び装置
CNB018205844A CN100481309C (zh) 2000-12-15 2001-12-14 用于检测有机体和天然产品状态以及分析具有主要和次要成分的气体混合物的方法和装置
PCT/EP2001/014804 WO2002058106A2 (fr) 2000-12-15 2001-12-14 Procede et dispositif pour evaluer l'etat d'organismes et de produits naturels et pour analyser un melange gazeux comprenant des composants principaux et des composants secondaires

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EP01986885A Withdrawn EP1342254A2 (fr) 2000-12-15 2001-12-14 Procede et dispositif pour evaluer l'etat d'organismes et de produits naturels et pour analyser un melange gazeux comprenant des composants principaux et des composants secondaires

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BR112013017419B1 (pt) 2011-01-05 2021-03-16 Purdue Research Foundation sistema e método para analisar uma amostra e método para ionizar uma amostra
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CL2012001566A1 (es) * 2012-06-11 2013-08-09 Univ De Santiago De Chile Univ Tecnica Federico Santa Maria Metodo analitico para verificar la edad de la carne de animales utilizando perfiles volatiles que comprende introducir una fibra de microextraccion en fase solida en un vial que contiene la carne picada que ha sido calentada, luego desorber en el puerto de inyeccion de un cromatografo de gases, separar los gases y determinar sus concentraciones.
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JP6948266B2 (ja) 2015-02-06 2021-10-13 パーデュー・リサーチ・ファウンデーションＰｕｒｄｕｅ Ｒｅｓｅａｒｃｈ Ｆｏｕｎｄａｔｉｏｎ プローブ、システム、カートリッジ、およびその使用方法
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WO2002058106A2 (fr) 2002-07-25
EP1342254A2 (fr) 2003-09-10
KR20030072361A (ko) 2003-09-13
KR100885654B1 (ko) 2009-02-25
US20040046567A1 (en) 2004-03-11
EP1217643A1 (fr) 2002-06-26
ATE408237T1 (de) 2008-09-15
DE50015353D1 (de) 2008-10-23
US6982416B2 (en) 2006-01-03
DK1217643T3 (da) 2009-01-19
JP4316883B2 (ja) 2009-08-19
CN1533585A (zh) 2004-09-29
WO2002058106A3 (fr) 2003-04-10
JP2004517340A (ja) 2004-06-10

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