EP1217643A1 - Méthode et dispositif pour la détermination de l' état d'organismes et de produits de la nature ainsi que pour l'analyse de mélanges présentant des composantes principales et secondaires - Google Patents

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

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Publication number
EP1217643A1
EP1217643A1 EP00127558A EP00127558A EP1217643A1 EP 1217643 A1 EP1217643 A1 EP 1217643A1 EP 00127558 A EP00127558 A EP 00127558A EP 00127558 A EP00127558 A EP 00127558A EP 1217643 A1 EP1217643 A1 EP 1217643A1
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EP
European Patent Office
Prior art keywords
gaseous mixture
sample
ion beam
components
mass spectrometer
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EP00127558A
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German (de)
English (en)
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EP1217643B1 (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 AT00127558T priority Critical patent/ATE408237T1/de
Application filed by V & F Analyse- und Messtechnik GmbH filed Critical V & F Analyse- und Messtechnik GmbH
Priority to EP00127558A priority patent/EP1217643B1/fr
Priority to DE50015353T priority patent/DE50015353D1/de
Priority to DK00127558T priority patent/DK1217643T3/da
Priority to CNB018205844A priority patent/CN100481309C/zh
Priority to US10/433,370 priority patent/US6982416B2/en
Priority to JP2002558304A priority patent/JP4316883B2/ja
Priority to KR1020037007736A priority patent/KR100885654B1/ko
Priority to EP01986885A priority patent/EP1342254A2/fr
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, the substances in the atmosphere surrounding them dispense one or more of these substances in a gaseous mixture be determined, a method for analyzing a gaseous mixture with main and secondary components, and a device for carrying them out Method comprising a mass spectrometer.
  • the object of the present invention is a method for analysis of gaseous mixtures to provide the rapid determination of Major and minor components of the gaseous mixture allowed.
  • Another object of the invention is a device for analyzing gaseous To provide mixtures for carrying out the above-mentioned processes is suitable and a quick analysis of samples of gaseous mixtures allowed, the components of which are present in a wide concentration range.
  • the invention is based on the knowledge that the above-mentioned tasks are met With the help of a mass spectrometer, the sample can be solved ion gaseous mixture to be analyzed acts in a high vacuum.
  • the present invention therefore provides a first method for assessing the condition of organisms and natural products, the substances in the surrounding Release atmosphere, available in which one or more of these substances be determined as components of a gaseous mixture, the determination by means of a mass spectrometer, in which the gaseous mixture acts on an ion beam in a high vacuum, and that at Determination obtained values are evaluated to determine the condition.
  • the method according to the invention can be used to assess the condition of living and dead organisms and their parts as well as natural products of all kinds become.
  • Natural products are natural in the sense of this invention Products such as fruit, vegetables, meat, cow's milk etc., through natural manufacturing processes products obtained such as Wine, beer, cheese, cooking oil etc., as well as through Refinement of natural products such as Coffee beans, Smoked ham etc. understood.
  • gaseous mixtures are mixtures of substances understood the other main components in gaseous form at room temperature Contain components that are in the form of the main components Gas phase.
  • Mass spectrometer in which an ion beam on a gaseous mixture in the High vacuum acts, for example from EP 0 290 711, EP 0 290 712 and DE 196 28 093 known.
  • the disclosure content of these publications is hereby incorporated Referred.
  • the method according to the invention has the advantage that from the one to be examined Organism or natural product, no samples taken artificially need to be, causing any injury to the organism or natural product is avoided. So it is a non-invasive procedure.
  • Another The advantage of the method is that the method for analyzing a sample takes only a short time in the range of a few minutes.
  • the method offers the advantage that when determining multiple components the gaseous mixture to be analyzed essentially no overlays (Interference) can be obtained in determining the components that a Prevent analysis of individual specific components.
  • the method for assessing the condition used by humans and animals has the advantage that no samples such as blood samples for the object to be examined must be taken, especially for carrying, because such sampling by trained personnel, in the case of humans, for example by doctors, be performed. In addition, such sampling is done by people and felt uncomfortable to animals.
  • the invention Method as a non-invasive method has the advantage that, on the one hand the sampling is not perceived as unpleasant and on the other hand by untrained personnel or by the test person himself.
  • the process according to the invention the exhaled air used by humans as a gaseous mixture.
  • This offers the advantage that on the one hand sampling can be carried out very easily and that on the other hand the substances obtained in the exhaled air the assessment of Condition of the test subject with regard to a variety of clinical pictures and Enable metabolic processes.
  • the process according to the invention the concentration of one or more of those contained in the gaseous mixture Substances quantified. Since the method according to the invention Determination by means of a mass spectrometer, in which the sample The quantities are a gaseous mixture which acts on an ion beam in a high vacuum of the certain substances linearly proportional to the detected signal, therefore the quantitative detection can be carried out in a simple manner.
  • the quantitative determination also offers the advantage that it allows further statements on the condition of the organism or natural product. In particular In the case of multiple measurements, changes in the Concentrations of substances and thus changes in the state of the organism or natural product.
  • the sample of the gaseous mixture without pretreatment to the mass spectrometer fed is fed.
  • This offers the advantages that, on the one hand, the time requirement for the Measurement of a sample is minimized and on the other hand no additional costs Pretreatment steps, such as concentrating the sample, arise.
  • the gaseous mixture of main components and secondary components to be analyzed the concentration of the main components being that of the secondary components by at least a factor of 10, preferably 50, more preferably 100.
  • the gaseous mixture to be analyzed each consisting of at least one main component in the concentration range of ⁇ 0.1 vol%, preferably ⁇ 1 vol%, and at least one secondary component in the concentration range of ⁇ 0.1 vol%, preferably ⁇ 0.03 vol%, the concentration of at least one in each case the main and secondary components are determined.
  • the concentration of at least one of the major and one of the minor components quantified is determined quantitatively.
  • concentrations are also more preferred the main components of the gaseous mixture to be analyzed essentially the same as that of atmospheric air.
  • all components of the gaseous mixture to be analyzed has a molecular mass of up to 500, preferably have a molecular mass of up to 200, quantitatively detected.
  • the ion beam that acts on the sample molecules in a high vacuum is an atomic one Ion beam.
  • the ion beam further preferably comprises ions which are in the electronic ground state and / or are in a selectively excited metastable state.
  • At least the ion beam that acts on the sample molecules in a high vacuum two ion beams with different ionization potential.
  • the ion beam which acts on the sample molecules in a high vacuum, an Hg ion beam.
  • the ion beam which acts on the sample molecules in a high vacuum, an Hg ion beam and additionally a Kr ion beam and / or a Xe ion beam.
  • the different ion beams further preferably act on the Sample molecules in a high vacuum.
  • the present process preferably uses substances with an ionization potential ⁇ 17 eV determined.
  • the evaluation of the values obtained is preferably carried out in such a way that the concentration of the secondary components on the concentration of at least one of the Main components is sourced.
  • the present invention further provides a second method for analysis a gaseous mixture with one or more major and minor components available, with at least one main component in each case Concentration range ⁇ 0.1 vol%, preferably ⁇ 1 vol%, and at least one Secondary component in the concentration range ⁇ 0.1 vol%, preferably ⁇ 0.03 Vol%, can be determined by means of a mass spectrometer, on which the sample the gaseous mixture is subjected to an ion beam in a high vacuum.
  • This method offers the advantage that it can be determined quickly and simultaneously of major and minor components of a gas mixture allowed and therefore allows comprehensive statements about the gas mixture.
  • the mass spectrometer is used for the evaluation data obtained a correlation between at least one Main component and at least one secondary component.
  • This offers for example the advantage that the evaluation of the data by standardization of the data of the secondary components to that of the main components.
  • the proportion of main components may indicate faulty ones Samples are closed and these are sorted out.
  • the present invention further provides an apparatus for analyzing gaseous mixtures are available, which a mass spectrometer with a Gas inlet system comprises, wherein from the sample to be analyzed the gaseous Mixture is generated from a molecular beam in an intermediate vacuum then a second molecular beam by means of a pressure gradient in a capillary is generated in a high vacuum, which is ionized by an ion beam, the pressure of the intermediate vacuum is kept constant.
  • the device according to the invention has the advantage that the in the high vacuum located analyzer of the mass spectrometer passing second molecular beam has a constant particle density. This way the viscosity of the second sample molecular beam kept constant. Furthermore, with the device reaches a high density of the second sample molecular beam, wherein simultaneously with the action of the ion beam on the sample molecular beam Single impact conditions prevail.
  • the sensitivity of the Mass spectrometers can be increased to the ppb range and at the same time Components of gaseous mixtures determined in the volume percentage range become.
  • the gas inlet system of the device according to the invention inert to the components contained in the sample of the gaseous mixture, so that the system is not rinsed before measuring a new sample got to.
  • At least the ion beam that acts on the sample molecules in a high vacuum two ion beams with different ionization potential.
  • the device according to the invention includes the ion beam, which acts on the sample molecules in a high vacuum, an atomic ion beam.
  • the ion beam further preferably comprises ions which are in the electronic ground state and / or are in a selectively excited metastable state.
  • the device according to the invention includes the ion beam, which acts on the sample molecules in a high vacuum, an Hg ion beam.
  • the device according to the invention includes the ion beam, which acts on the sample molecules in a high vacuum, an Hg ion beam and additionally a Kr ion beam and / or a Xe ion beam.
  • the different ion beams further preferably act on the Sample molecules in a high vacuum.
  • the methods according to the invention preferably include the use of device according to the invention.
  • an increased content of methane in the breathing air can be caused by the Improper colonization of the small intestine can be caused by colon bacteria, which then produce methane in the small intestine, which enters the lungs and through the bloodstream to get into the exhaled air.
  • increased methane values can also be found in certain Types of malnutrition occur.
  • the content of acetone in the exhaled air of diabetics is increased.
  • Cancer cells in the body can increase the amount of aldehyde in the body Exhaled air come.
  • the propanol content is in relation to the ethanol content the exhaled air is increased by a factor of 10.
  • the pentane level in the exhaled air is a measure of changes in lipid activity in the body and related diseases. For example, at rheumatic inflammation, in the case of lung injuries caused by inhalation of high Oxygen concentrations, in heart attack patients and in patients with cancer Respiratory organs an elevated pentane level was detected.
  • the pentane content in the Exhaled air can also be increased in schizophrenia and multiple sclerosis. Furthermore is a linear relationship between the age of subjects and the pentane content in their exhaled air has been determined.
  • the CO content is increased in the exhaled air.
  • ketones in the exhaled air is detected if increased by Lipolysis the supply of fatty acids in the body is high. This can be different Causes such as hunger or insulin stomach (diabetes mellitus) are attributed become.
  • ketonuria an increased concentration of ketone bodies (acetoacetate, R3 hydroyxbutyrate and acetone). This is due to poor glycogen the liver due to failure of carbohydrate metabolism.
  • Ketoacidosis such as that of coma diabeticum, hunger or Alcoholism is present, an increased content of propionic acid and butyric acid in of the exhaled air can be determined.
  • Phenols can be determined in the exhaled air.
  • the metabolic products of bacteria in the human body such as CO 2 and H 2 (Escherichia coli) or H 2 S (Proteus) can also be found in the exhaled air. Volatile fatty acids can be detected particularly in the case of infection by clostridia (gas fire bacteria).
  • an increased content of H 2 in the exhaled air can be determined after their intake by test subjects.
  • the method according to the invention can thus be used to diagnose clinical pictures and metabolic disorders of all kinds are used in the human body.
  • monitoring can be carried out by the method according to the invention the metabolism of organisms when taking pharmaceuticals, monitoring of therapeutic measures such as the continuous control of Healing processes, as well as for monitoring provocation tests in which a substance is administered in a certain (high) dose and the reaction of the body is followed up on this substance.
  • the method according to the invention is not based on the analysis of the exhaled air from People limited, but it can also, for example, samples of human gaseous mixtures of other nature such as, for example, the vapors and sweat, as well as the gas phases of urine, blood, faeces and other body fluids.
  • Sampling in the case of analysis of the sweat can be done for example take place that this is taken up by the test person by means of a cotton ball, and the gas phase over the cotton ball is analyzed.
  • the method according to the invention can be used for quality control of all kinds of natural products, where, for example, when certain gaseous substances appear in the gas phase above the natural product, decomposition of the product can be concluded. For example, when analyzing the gas phase over fresh meat, first lactic acid is found, then with increasing age NH 3 and finally S-compounds.
  • Another conceivable application of the method according to the invention is detection of animals suffering from BSE, for example, about the changed composition from their exhaled air.
  • Figure 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.
  • Sampling and sample feeding to the mass spectrometer can be carried out at one so that a direct connection between the gas space in which the gas mixture to be analyzed is located and manufactured in the mass spectrometer becomes.
  • this can be done using a Breathing mask happen, as described for example in WO 99/20177.
  • the breathing air exhaled by a test subject becomes direct through this breathing mask fed to the mass spectrometer.
  • This allows online real-time data of the test person's breathing air components are obtained because the Response time of the mass spectrometer to changes in the gaseous feed Mix is in the range of milliseconds. For example rapidly progressing metabolic changes of the test person such as the rapid degradation of an easily degradable pharmaceutical is directly observed become.
  • This procedure can be used, for example, in emergency medicine are used, for example for the detection of rapidly deteriorating Health conditions.
  • Another application of the online process can be Real-time monitoring of metabolic processes, for example after a provocative test his.
  • Sampling can also be done using the subject and mass spectrometer are separated from each other in time and / or space, so that the exhaled air sample must first be kept in a suitable container.
  • Vials made of glass with a preferred volume of 20 ml are used.
  • Sampling is carried out in such a way that the test person is even (preferably by Nose) and through a common drinking straw about 1 to 2 cm above the bottom of the vessel exhales into the vial.
  • the vial is then sealed airtight. This is preferably done with a crimp cap, which is fixed with the after sampling Glass vial is crimped. It was found that a time of a few seconds, in which the vial is still unlocked after the subject exhales has no negative effects, such as a change in composition have the gaseous mixture exhaled by the subject.
  • the crimp cap is preferably designed so that it is in the area where a direct Contact of the cap with the interior of the vessel, i.e. with the exhaled gaseous mixture takes place, is completely covered with Teflon.
  • the opening the glass vial is advantageously designed so that its upper edge is a conical has a sloping shape.
  • the crimp cap can thus be designed in this way be that it includes an outer ring of butyl rubber that adapts to the conical outer wall of the vial rests elastically and thus acts as a seal. This preferred embodiment of the glass vial seal is the maximum Inertness to the gaseous mixture exhaled by the test person guaranteed.
  • composition of the ambient air in which the test person is located and to be able to determine any contamination in this ambient air becomes parallel to the glass vial filled with the subject's exhaled breath a second vial that did not come into contact with the breath of the test person is closed in the vicinity of the subject (comparison vial).
  • the test person's exhaled air can last several days in the sealed glass vials can be kept without loss of quality. This can serve, for example, the Transport samples from the treating doctor to the evaluation laboratory. That kind of Sampling is also known as the offline method.
  • the sampling points the advantage of being simple, even by untrained personnel can be carried out.
  • Sampling can also be used to determine the condition of natural products done offline or online. For example, offline sampling a glass vial that spends some time with the gas phase immediately above that to be examined Product has been in contact.
  • the samples are first for example mounted on an autosampler.
  • This can be a modified one, for example CNC system of the type "step-4 milling machine basic 540", which is modified in this way was that they have 70 samples, each consisting of 70 sample and comparison vials, fully automatically is sampling.
  • the sample is preferably placed on a prior to being fed to the mass spectrometer higher temperature than room temperature, more preferably 65 ° C, heated.
  • the gas passes through a hot capillary that is at a higher temperature than the autosampler has to the gas inlet system, which in turn is a higher temperature than the capillary has.
  • the amount of gas passing through the capillary is a maximum of about 5 ml / min.
  • the gas injection system of the mass spectrometer is designed to compensate for pressure and viscosity fluctuations, so that in the analyzer of the mass spectrometer always the same particle density is injected.
  • Mass spectrometers are used to analyze the gaseous sample mixtures, in which an ion beam acts on the sample molecules in a high vacuum. With this type of mass spectrometer, no calibration is necessary to obtain quantitative concentration values for the individual masses detected. The concentrations are therefore given directly in absolute terms.
  • the mass spectrometer according to the invention also allows linear detection of the concentrations of the masses in the concentration range from 10 -7 vol% (ppb) up to 10 2 vol%, ie to a range of 10 9 . This means that the quantities of the determined masses are obtained directly from the measurement.
  • the components of the gaseous mixture are measured accordingly in the mass spectrometer their molecular mass is detected.
  • the sample gas is in a High vacuum chamber introduced and converted into ions, which subsequently accordingly their mass are selected by electromagnetic fields and in be counted using 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 an 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 therefore only detected. This enables a quantitative determination of components that are only present in traces up to 10 -7 vol%. Furthermore, very few compounds are fragmented by the mercury ion beam.
  • the mass spectrometer uses different ionization levels, i.e. at least two primary ion beams, to distinguish 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 in which the molecule is transformed into an ion.
  • An Hg ion beam together with a krypton ion beam are further preferred and / or a xenon ion beam.
  • the sequence of the different Ion beams during the measurement can be in any order.
  • the molecules N 2 and CO which have identical mass, can differentiate between 14.2 eV (N 2 ) and 13.7 eV (CO) due to their different ionization potentials become.
  • Another separation effect can be achieved by the formation of defined fragment ions.
  • a distinction is made between the mass-identical molecules methanol and O 2 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 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 all masses up to a molecular weight after ionization of 500, preferably 200, can be 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, Nitrogen monoxide, protonated water as water adduct, acetyl group, Formyl group, formaldehyde * protonated water, pyridine, pentane, cyclopentane, Methyl ethyl ketone, propionic acid, butyric acid, methyl mercaptan, ethylene, nitrous oxide, Propane and sulfur dioxide are assigned.
  • the method according to the invention also offers the advantage of chemical compounds of all kinds, ie. for example acids and bases, polar and non-polar Substances that can be measured simultaneously with one measurement.
  • the CO 2 content of the sample is first determined. With a sampling temperature of the sample gas mixture from the vial of 65 °, a CO 2 content of approximately 2 to 3.5 vol% normally results. It was found that this CO 2 value only fluctuates in the range of about 10% in normal exhalation samples. Therefore, if the measured CO 2 content is significantly outside this normal range, it can be assumed that either the sample vial was improperly closed or handled improperly or that the test person used the wrong breathing technique so that the exhaled air from the lungs was not recorded. Using this and similar criteria, falsified samples can be discarded.
  • the measuring process is carried out at least five times for a sample or comparison vial repeated (5 cycles) and the mean values from these cycles were formed.
  • One cycle takes about a minute to measure 200 masses.
  • the sample vial is first used and then the comparison vial certainly.
  • the mean values are obtained from the results of the measurement cycles educated.
  • the determination of the comparison vial shows that contamination of the ambient air of the subject, the sample can either be discarded or the amount of the component present as contamination in the exhaled air sample can be obtained from the difference (probevial minus comparison vial).
  • This Approach makes it possible to eliminate any contamination in the vials because the difference from same contaminations gives zero and results from that Breathing air and contamination exist, correspond to the actually exhaled value.
  • the data are evaluated in such a way that the measured quantitative values for the components, either by mass or by chemical nature after are determined, compared with the normal values of the respective component become. This can result in deviations in the content of components in the exhaled air of the respective test person from the normal state. values then outside the normal range of the respective component Allow conclusions to be drawn about the subject's state of health.
  • the normal values can be measured, for example, by series measurements on a large number of subjects to determine the normal state of human breathing air be preserved.
  • the normal values can also be found in the literature, as far as these are known.
  • the normal values generally include a certain one Area.
  • the quantitative values measured for the components are preferably standardized to the value of one of the main components of the gaseous mixture, preferably CO 2 .
  • the standardization establishes a relationship between the content of the individual components and the actually exhaled amount of breathable air per subject. This has the advantage that values between different test subjects and also values obtained by temporally offset measurements of a subject's breathing air can be compared with one another.
  • the value determined after the standardization is further preferred by the value for human subjects known maximum value divided. This results in each case Values for the individual components between 0 to 1. This makes the evaluation further simplified and clearer for the evaluating specialist staff (doctors).
  • Correlations established to capture certain clinical pictures. For example the ethanol / propanal ratio can be determined, so statements to enable a possible hepatitis infection.
  • a particular advantage of the method when determining all components in a certain mass range is that an overall overview of the most varied clinical pictures and metabolic processes is obtained. For example, it is known that in schizophrenia patients both the pentane content and the content of H 2 S and CS 2 in the exhaled air are increased, so that when these components are determined simultaneously, other clinical pictures can be excluded in which only the content of one of these components increases is.
  • the observable metabolic processes can be both about build-up processes (anabolisms) as well as about breakdown processes (catabolisms) act.
  • the inventive method has the additional advantage that it can also be carried out by untrained personnel, resulting in cost savings leads.
  • the evaluation of the measurements is advantageously carried out with IT support.
  • One embodiment of the device according to the invention comprises a gas inlet system with a flexible gas transfer capillary (3), which is preferably made of fused silica is 250 microns inside diameter and a quarter inch Teflon tube is placed. There is also a in the Teflon tube Heating wire.
  • the capillary (3) has a cannula (2) for taking samples from a sample vial (1) connected.
  • the various components up to the pinhole (5) each have a higher temperature in the direction of the gas flow. preferably, the sample vial (1) to 65 ° C, the cannula (2) to 85 ° C and the Gas transfer capillary (3) heated to 100 ° C.
  • the small diameter the capillary also allows the smallest gas quantities from the sample vial can be removed.
  • the gas inlet system has the advantage that it the gaseous mixtures to be analyzed is inert towards and therefore none Has memory effects. Therefore, it is not necessary to rinse the System necessary.
  • the gas flow through the capillary (3) is preferably limited to a maximum of 5 ml / min. 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 changed from a robot to the desired sample vial controlled.
  • gas switching valves (4) in the area in front of the pinhole (5) the zero gas and calibration gases, preferably up to a maximum pressure of 1.5 bar can be added. However, the total gas flow must be greater than that Be back diffusion.
  • the Pump (9) which is preferably a two-stage, oil-free vacuum pump with 0.2 to 200 mbar is its own pressure, a pressure of about 20 mbar is generated.
  • the cannula (2) when the cannula (2) is inserted into the sample vial (1), it is at approximately atmospheric pressure there is the gaseous mixture to be analyzed in the direction of the Negative pressure through the gas transfer capillary (3) to the pinhole (5), whereby in the intermediate vacuum chamber (24) behind the pinhole (5) a first molecular beam (6) is generated. In the area in front of the further capillary (10), which is also made of fused silica, this jet (6) has laminar flow.
  • the pressure of about 20 mbar is a Proportional control valve (8), the secondary air or inert gases flow into this room can be kept exactly at a constant value.
  • the control of the proportional control valve (8) is preferably carried out via a capacitive absolute pressure sensor (7), the pressure within the intermediate vacuum chamber (24) is accurate and independent of the composition of the gas. This ensures that Pressure fluctuations of the sample molecular beam (6), as in the repeated Measurements from the same sample vial occur, 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 into the further capillary (10) constant particle density.
  • one end of the capillary (10) which has a preferred inside diameter of 250 Has micrometers and heated to a temperature above 100 ° C, preferably 220 ° C is.
  • the heating of the capillary (10) causes the desorption times be kept as low as possible.
  • the other end of the capillary (10) is located in the high vacuum chamber (22), in which a high vacuum, preferably of at least 10 -7 mbar, is generated by, for example, a turbomolecular pump (23).
  • the capillary end is located just before an open slot in the octopole guide field (16) in the charge exchange chamber (17). Due to the pressure gradient in the capillary (10), the sample molecular beam (6) passes through the capillary (10) into the charge exchange area (17) of the high vacuum chamber (22), at the end of the capillary (10) it receives a second molecular beam ( 11) forms.
  • the primary ion beam (12) for ionizing the molecular beam (11) is formed that from one of the gas reservoirs (13) of mercury, krypton and xenon Gas removed with reduced pressure and to the electron impact source (14), the hot tungsten filament, Includes anode and pull-out screen, is performed.
  • the resulting primary ion beam (12) is through a first octopole guidance field (15) performed. Only high molecular weights (primary ions) guided and suppressed the masses of impurities in the gas reservoirs (13), to achieve a high signal-to-noise ratio for the substances to be measured.
  • the primary ion beam (12) is then carried on in a second octopole guide field (16) which has the same transmission for all types of molecules.
  • a second octopole guide field (16) which has the same transmission for all types of molecules.
  • the charge exchange zone (17) in which the primary ion beam (12) strikes the sample molecular beam (11).
  • a sample molecule ion beam (18) is generated in individual burst processes at a pressure of on average 10 -4 mbar, the sample molecules then being separated in the quadrupole analyzer (19) according to their mass / charge ratio.
  • the sample molecule ions are then converted into electronically processable electron pulses in the ion detector (20).
  • the electron pulses are then coupled out for the counting electronics (21).
  • test persons carried out exhaled breath analyzes in a clinical test.
  • samples of the respiratory air of the respective test person were taken in such a way that the test person breathed in and out evenly a few breaths through the nose, then held the air for two to three seconds and then the air evenly through a straw, the end of which was one to two centimeters exhaled above the bottom of a glass vial with a volume of 20 cm 3 .
  • sample vial was then each crimped using crimping pliers locked. This closing took place after about five seconds at the latest after the subject exhaled into the vial.
  • a second vial (comparison vial) was placed in the area the subject closed without the atmosphere in the comparison vial had come into contact with the subject's exhaled air.
  • Sample and comparison vials were each placed in an autosampler and there Pre-thermostatted to 65 ° C for at least 10 min.
  • the samples were tested first and then the comparison vial of the test persons using the embodiment described above the device according to the invention.
  • the measurement of each Vials took place in at least six cycles, i.e. the content of each vial was determined at least six times. From the at least obtained for the respective mass six values were then averaged.
  • 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 mean values were then normalized to the value of CO 2 by dividing the mean values by the value obtained for CO 2 .
  • Lines 1 to 9 show the values for subjects 1 to 9. In The respective values for the masses are shown in the columns. Where an assignment chemical compounds could be made, this is instead of the mass Connection specified.
  • This example shows that the condition of a subject with a serious health disorder against which other subjects can be determined.

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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)
  • Measurement Of The Respiration, Hearing Ability, Form, And Blood Characteristics Of Living Organisms (AREA)
  • Investigating Or Analyzing Non-Biological Materials By The Use Of Chemical Means (AREA)
  • Investigating Or Analysing Materials By The Use Of Chemical Reactions (AREA)
  • Investigating Or Analyzing Materials By The Use Of Fluid Adsorption Or Reactions (AREA)
  • Sampling And Sample Adjustment (AREA)
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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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
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
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
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
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
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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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

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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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EP (2) EP1217643B1 (fr)
JP (1) JP4316883B2 (fr)
KR (1) KR100885654B1 (fr)
CN (1) CN100481309C (fr)
AT (1) ATE408237T1 (fr)
DE (1) DE50015353D1 (fr)
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WO (1) WO2002058106A2 (fr)

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JP2010022555A (ja) * 2008-07-18 2010-02-04 Sharp Corp 呼気センサを用いた刺激コントロールシステム
US8704167B2 (en) 2009-04-30 2014-04-22 Purdue Research Foundation Mass spectrometry analysis of microorganisms in samples
US9500572B2 (en) 2009-04-30 2016-11-22 Purdue Research Foundation Sample dispenser including an internal standard and methods of use thereof
US8859956B2 (en) * 2009-04-30 2014-10-14 Purdue Research Foundation Ion generation using wetted porous material
BR112013017419B1 (pt) 2011-01-05 2021-03-16 Purdue Research Foundation sistema e método para analisar uma amostra e método para ionizar uma amostra
US9157921B2 (en) 2011-05-18 2015-10-13 Purdue Research Foundation Method for diagnosing abnormality in tissue samples by combination of mass spectral and optical imaging
US9546979B2 (en) 2011-05-18 2017-01-17 Purdue Research Foundation Analyzing a metabolite level in a tissue sample using DESI
US8895918B2 (en) 2011-06-03 2014-11-25 Purdue Research Foundation Ion generation using modified wetted porous materials
RU2473907C1 (ru) * 2011-12-30 2013-01-27 Федеральное бюджетное учреждение науки "Федеральный научный центр медико-профилактических технологий управления рисками здоровью населения" (ФБУН "ФНЦ медико-профилактических технологий управления рисками здоровью населения") Способ оценки негативного воздействия бензола и фенола, поступающих с атмосферным воздухом, на нарушение функций глутатионовой системы детского организма
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.
US9733228B2 (en) 2013-01-31 2017-08-15 Purdue Research Foundation Methods of analyzing crude oil
WO2014120411A1 (fr) 2013-01-31 2014-08-07 Purdue Research Foundation Systèmes et procédés pour analyser un échantillon extrait
WO2014209474A1 (fr) 2013-06-25 2014-12-31 Purdue Research Foundation Analyse par spectrométrie de masse de micro-organismes dans des échantillons
CN103529152B (zh) * 2013-10-15 2015-07-01 中国工程物理研究院化工材料研究所 一种基于质谱仪的自反馈气体定量装置及其使用方法
US9786478B2 (en) 2014-12-05 2017-10-10 Purdue Research Foundation Zero voltage mass spectrometry probes and systems
CN107960130A (zh) 2015-02-06 2018-04-24 普度研究基金会 探针、系统、盒及其使用方法
JP6547843B2 (ja) * 2015-12-17 2019-07-24 株式会社島津製作所 イオン分析装置
EP3418714A1 (fr) 2017-06-19 2018-12-26 V&F Analyse- und Messtechnik GmbH Dispositif et procédé d'acheminement partiel d'un échantillon de liquide comprenant plusieurs composants et procédé de détermination en ligne et d'analyse desdits composants
JP6344783B1 (ja) * 2017-06-21 2018-06-20 エフビートライアングル株式会社 ガス分析に基づく評価システム

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Publication number Publication date
KR100885654B1 (ko) 2009-02-25
DE50015353D1 (de) 2008-10-23
JP4316883B2 (ja) 2009-08-19
CN1533585A (zh) 2004-09-29
JP2004517340A (ja) 2004-06-10
US20040046567A1 (en) 2004-03-11
KR20030072361A (ko) 2003-09-13
WO2002058106A3 (fr) 2003-04-10
EP1342254A2 (fr) 2003-09-10
DK1217643T3 (da) 2009-01-19
ATE408237T1 (de) 2008-09-15
WO2002058106A2 (fr) 2002-07-25
CN100481309C (zh) 2009-04-22
US6982416B2 (en) 2006-01-03
EP1217643B1 (fr) 2008-09-10

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