KR20100083785A - Chemical ionization reaction or proton transfer reaction mass spectrometry with a quadrupole or time-of-flight mass spectrometer - Google Patents

Abstract

A system and methods are described for generating reagent ions and product ions for use in a mass spectrometry system. Applications for the system and method are also disclosed for detecting volatile organic compounds in trace concentrations. A microwave or high-frequency RF energy source ionizes particles of a reagent vapor to form reagent ions. The reagent ions enter a chamber, such as a drift chamber, to interact with a fluid sample. An electric field directs the reagent ions and facilitates an interaction with the fluid sample to form product ions. The reagent ions and product ions then exit the chamber under the influence of an electric field for detection by a mass spectrometer module. The system includes various control modules for setting values of system parameters and analysis modules for detection of mass and peak intensity values for ion species during spectrometry and faults within the system.

Description

Chemical ionization or quantum transition reaction mass spectrometry using quadrupole or time-of-flight mass spectrometry

The present invention relates generally to mass spectrometry, and more particularly, to mass spectrometry in which reagent ions are formed using microwave or high frequency radio frequency plasma and to applications therefor.

Mass spectrometry generally relates to the implicit determination of the mass value of a particle by direct measurement of the mass value of the particle or by measurement of other physical quantities using spectral data. Mass spectrometry often involves determining the mass to charge ratio of an ionized molecule or component. If the charge of an ionized particle is known, the mass value of this particle can be determined from the spectrum of mass values.

A system for performing mass spectrometry is known as a mass spectrometer. Mass spectrometer systems generally include an ion source, a mass filter or separator, and a detector. For example, a sample of molecules or components can be ionized by electron bombardment in an ion source to produce ions. Ions with different mass values are separated into a mass distribution or spectrum by a mass spectrometer, for example by applying an electric or magnetic field to the ions. The detector may collect ions, observe and / or record the mass distribution. The relatively large mass values of the spectrum are used to determine the identity or mass of the molecules or components of the sample and the composition of the sample.

There are many different types of mass spectrometers, including a category called ionic molecular reaction mass spectrometers (IMR-MS). Within this category, several techniques exist, including quantum transition reaction mass spectrometry (PTR-MS) and selective ion flow tube mass spectrometry (SIFT-MS). This category generally refers to how ions are produced. For example, a quantum transition reaction mass spectrometer includes an ion source that produces a reaction reagent, typically hydronium ions (H ₃ O ⁺ ), for example to transfer charge to a sample component by quantum transition. In the selective ion flow tube mass spectrometer, the carrier gas transports the filtered ions along the flow tube. In a quantum transition reaction mass spectrometer sold by Ionicon Analytik GmbH, Innsbruck, Austria, a hollow cathode tube is used as an ion source to generate reagent ions by applying a DC plasma discharge to water vapor.

Some mass spectrometry systems are classified by the type of mass spectrometer used. For example, some mass spectrometry systems are based on tandem techniques that use other analytical techniques in combination with mass spectrometry equipment. One example is gas chromatography mass spectrometry (GC-MS), which separates the components of a sample using a gas chromatography column prior to analysis by mass spectrometry.

Mass spectrometry can be used to determine the amount of volatile organic compounds (VOCs) in a sample. VOC measurements have become important, even in the presence of small amounts of VOCs, because these VOCs can function as important diagnostic indicators in many different applications and can adversely affect human health. For example, if the concentration of VOC exceeds a certain level, it may adversely affect human health, such as respiratory disease. In addition, the type and amount of VOCs in a particular sample may indicate the presence of explosives, harmful chemicals, combustibles, pathogens, debris or contaminants, fire suppressants, and abuse drugs. In addition, monitoring the presence and amount of VOCs is useful in industrial processing such as biochemical or pharmaceutical manufacturing processes.

Conventional mass spectrometry systems generally have several drawbacks and are inherent when applied to the detection of VOCs. For example, mass spectrometry systems employing gas chromatography are not suitable for continuous real-time monitoring of fluid samples due to relatively slow sample analysis. In addition, previous mass spectrometry systems often require sample collection from the site prior to sample analysis in a lab-based environment rather than in situ analysis. Previous mass spectrometry systems are relatively insensitive to the low concentration component of the sample, for example, because the ion source does not produce a sufficient amount of ions to produce an identifiable mass spectrum for the low concentration component. Mass spectra for low concentration components in such systems are often indistinguishable from noise due to dynamic range limitations, or overwhelmed by peak interference from noise or high concentration components caused by electronic or mechanical equipment. Mass spectrometry systems with appropriate levels of sensitivity may facilitate the detection of the presence of VOCs, but may interfere with other compounds present and thus may not clearly identify a particular compound or species.

There is a need for a robust mass spectrometry system that can provide continuous and real-time field analysis. There is also a need for a system that can reliably determine the presence and identification of a VOC in a particular sample, including a small amount of VOC.

Systems and methods employing the invention feature mass spectrometry that uses microwave energy or high frequency RF energy to generate reagent ions, such as, for example, hydronium ions for interacting with a fluid sample. The use of microwave energy is known to produce reagent ions such as hydronium in greater amounts than other known ionization methods (e.g. radioactive sources are used), while avoiding electrode corrosion and instability associated with DC discharge sources. Increasing the amount of reagent ions improves system sensitivity, facilitating quantitative analysis and / or identification of individual VOCs even at small amounts. High frequency RF energy also exhibits advantages similar to those obtained when generating reagent ions using microwave energy in mass spectrometry. The invention also relates to systems and methods for the real-time measurement of VOCs at relatively high pressures, for example at pressures above about 100 millibars (about 10,000 Pascals).

The system and method of practicing the present invention may, in some embodiments, be used to detect VOCs at a concentration of about parts-per-trillion by volume (pptV). In some embodiments, the module analyzes and classifies specific VOCs detected based on the obtained mass spectra. System components used in embodiments of the present invention are suitable for portable mass spectrometry and / or field applications. The concepts described herein can be used in mass spectrometry systems employing chemical ionization reaction mass spectrometry (CIRMS) techniques or quantum transition reaction mass spectrometry (PTR-MS) techniques.

In some embodiments, the present invention includes an analysis or control module for processing data obtained, detected, or collected during system operation. For example, some systems include a multivariate analysis module to facilitate detection and identification of VOCs based on mass spectra. In addition, multivariate analysis modules can be used to monitor mass spectrometry systems or detect defects in such systems. In addition, a control module or feedback loop can be used to control the production of reagent ions and sample ions and their throughput in the mass spectrometry system, for example, by controlling various process parameters of the mass spectrometry system. These parameters include various electric fields, pressure values, ion and gas phase flow rates and ion energy. The invention also relates to a coupling, connection, or interface between various system components to influence the movement of reagent ions, sample components, and product ions through a mass spectrometry system.

The sensitivity of the quantum transition reaction mass spectrometer and the chemical ionization reaction mass spectrometer described herein may be varied based on various system parameters. The sensitivity can be altered based on the reagent ion concentration (eg, hydronium ion concentration) in the drift region.

The E / N ratio (expressed as Townsends (Td)) of the electric field to the concentration of neutral particles in the drift region can affect the sensitivity of the analyzer. The E / N ratio is a function of the electric field and pressure (eg gas density) in the drift region. The E / N ratio affects the time required for ions to cross the drift region.

Sensitivity is affected by the intensity of the ion beam reaching the mass spectrometer after leaving the drift region (consisting of reagent ions and product ions). This is a function of transition optics (eg, electrode / lens aperture shape), electric field and pressure therapy (pumping) in the transition region which affects beam focusing and beam transmission properties.

The sensitivity can be varied based on the ratio of the partial pressure of the large volume sample gas and the neutral reagent species in the drift region. The quantum transfer rate constant (k) for the gas sample species being monitored affects the sensitivity. The length of the drift region affects the sensitivity, because the longer the drift region, the longer the time required for the material to cross the drift region, and thus the chance of reacting the reagent ions with the sample species. Because it needs more. In addition, sensitivity is influenced by various mass spectrometry related sensitivity factors (eg, ion transmission / mass discrimination, detector / preamplifier gain and signal to noise ratio).

In one aspect, the invention relates to a system. The system includes a microwave or high frequency RF energy source for ionizing particles of the gaseous reagent by microwave or RF energy to form one or more reagent ions. The system also includes a chamber that includes an inlet port that allows a sample to enter the chamber to interact with one or more reagent ions from a microwave or high frequency RF energy source to form one or more product ions. The chamber has an electromechanical generated therein. In addition, the system collects one or more product ions and one or more reagent ions to facilitate determination of respective mass and / or peak intensity values of the product and reagent ions, the quadrupole mass spectrometer module disposed relative to the exit orifice of the chamber. It includes.

In some embodiments, the microwave energy source comprises a microwave plasma generator. The high frequency RF energy source may comprise a capacitively coupled RF plasma generator. In some embodiments, the reagent ions include hydronium ions, oxygen ions, or nitrous oxide. The sample may comprise one or more volatile organic compounds (VOCs).

Some embodiments of the system feature a set of electrodes disposed relative to the chamber to create an electromechanical in the chamber. The electromechanical facilitates the interaction between the reagent ions and the sample and allows product and reagent ions to pass through the exit orifice of the chamber. The set of electrodes can be disposed radially with respect to the axis of the chamber, and the electromechanical directs the product ions and reagent ions approximately in the axial direction. In some embodiments, the control module is in communication with the set of electrodes. The control module is operable to determine the value of the electromechanical (or electromechanical gradient) in the chamber based on the operating parameters of the system.

The system can include a mass flow controller, a capillary, or a leak valve to determine the amount of sample entering the chamber. The system can include a mass filter disposed between the chamber and the microwave or high frequency RF energy source to selectively allow reagent ions to be transferred into the chamber. An example of a suitable mass filter is a quadrupole mass filter. In some embodiments, the system is operable to analyze data from the quadrupole mass spectrometer module and includes a multivariate analysis module in communication with the system.

The microwave energy source is disposed within the microwave generator, the resonator portion, the resonator portion and one or more chokes through which the tube passes to reduce the amount of microwave energy in the gaseous reagent source, chamber, or both. It may include. In some embodiments, the system includes a control module in communication with the system that is operable to change the input parameter of the system based in part on the operating parameter of the system. These parameters may include the composition of the sample, the pressure of the chamber, the rate of product or reagent ions passing through the chamber, the flow rate of sample or reagent ions into the chamber, the energy of the product or reagent ions, reagent ions, product ions, Or chemical composition of the sample, or any combination thereof. In some embodiments, the control module can be operable to change the input parameter of the set of electrodes generating an electromechanical within the chamber based in part on the operating parameter.

In some embodiments, the system includes a control module in communication with the system to detect or identify a deficiency in an operating parameter of the system. The control module may change the value of the operating parameter based in part on the detection or identification of the defect. The system can include a control module in communication with the system to monitor the system. The control module sets or adjusts the value of the operating parameters of the system in response to the monitoring, and the control module is based on a multivariate statistical analysis algorithm. In some embodiments, the control module includes a multivariate statistical analysis module. The multivariate statistical analysis module can be used for process monitoring and / or defect detection in mass spectrometry systems. The multivariate statistical analysis module can be used for detection and / or identification of defects. In some embodiments, the multivariate statistical analysis module may be used to interpret mass spectral data (eg, of the mass spectrum) and may be used to identify components from constituent peaks of the mass spectrum. The multivariate statistical module can be used with quadrupole mass spectrometers or time-of-flight mass spectrometers. In some embodiments, a control module or multivariate statistical analysis module is used to detect and / or identify defects in the system, interpret data and / or identify, for example, components from constituent peaks of the mass spectrometer. Or analyze.

The system may also include an extraction electrode disposed relative to the chamber. The extraction electrode defines an orifice through which reagent or product ions pass toward the quadrupole mass spectrometer module. In addition, the extraction electrode is operable to specify energy values of reagent ions or product ions for collection by the quadrupole mass spectrometer module. Some embodiments of the system feature a lens assembly disposed relative to the chamber to focus reagent ions and product ions into an extraction orifice that facilitates passage of reagent ions and product ions to the mass spectrometer module.

In another aspect, the present invention relates to a method of generating one or more reagent ions for a quantum transfer reaction mass spectrometer or a chemical ionization reaction mass spectrometer. The method includes supplying a gaseous reagent and providing microwave energy to the gaseous reagent to produce one or more reagent ions.

The method may also comprise directing one or more reagent ions to a region for interacting with the components of the sample to form product ions. Reagent ions can be generated by microwave plasma. The gaseous reagent may comprise water vapor, oxygen, or nitrous oxide, and the reagent ions may comprise hydronium ions, oxygen ions, or nitrous oxide ions. In some embodiments, microwave energy is provided by radiation or electromagnetic waves having a frequency greater than about 800 MHz.

In another aspect, the present invention relates to a method of generating one or more reagent ions for a quantum transition reaction mass spectrometer or a chemical ionization mass spectrometer. The method includes supplying a gaseous reagent and providing high frequency RF energy to the gaseous reagent to generate reagent ions.

In some embodiments, RF energy is provided by electromagnetic waves between about 400 kHz and about 800 MHz. Reagent ions can be generated by capacitively coupled RF plasma.

In another aspect, the present invention relates to a method. The method includes supplying a gaseous reagent to the plasma region, and providing microwave or high frequency RF energy to the gaseous reagent in the plasma region to form one or more reagent ions. The method includes interacting reagent ions with a gas sample to produce one or more product ions. The method also includes directing the product ions and reagent ions to the collector region of the quadrupole mass spectrometer module, and determining, by the mass spectrometer module, values of the mass and / or peak intensities of the product and reagent ions. .

Another aspect of the invention relates to a mass spectrometry system. Mass spectrometry systems include means for generating one or more reagent ions from a gaseous reagent source by providing microwave or high frequency RF energy to the gaseous reagent. The system also includes means for interacting the sample with the reagent ions to form one or more product ions. The system includes means for including an electromechanical to direct product ions and reagent ions to the collector region. The system also includes means for communicating with the collector region to determine the value of the respective mass and / or peak intensity of product ions and reagent ions.

In one aspect, the invention relates to a system. The system includes a microwave or high frequency RF energy source for ionizing particles of gaseous reagents by microwave or RF energy to form one or more reagent ions. The system also includes a chamber for sample input to interact with reagent ions from a microwave or RF energy source to form one or more product ions. The system also includes a mass spectrometer module disposed relative to the outlet orifice of the chamber. The mass spectrometer module includes a flight zone in which product ions or reagent ions move and define the path length. The mass spectrometer module also includes a collector region for receiving product ions or reagent ions from the flight region. The mass value of product ions or reagent ions is determined based on the amount of time that product ions and reagent ions traverse the path length.

In some embodiments, the mass spectrometer module also includes an ion beam regulator disposed relative to the exit orifice of the chamber such that the flow of product ions and reagent ions pulses towards the flight zone. The mass spectrometer module also includes an optical system disposed in the flight zone to increase the value of the path length through which product and reagent ions travel. The ion beam controller can regulate the flow of product ions and reagent ions by a pseudo random number binary arrangement provided from the controller. In some embodiments, the analysis module performs a maximum likelihood signal processing algorithm on the data received from the mass spectrometer module to determine mass and / or peak intensity values of product ions and reagent ions. The analysis module may deconvolute the data received from the mass spectrometer module to determine the mass and / or peak intensity values of the product ions or reagent ions. The collector region may comprise a stacked microchannel plate detector or an anode detector operating in a pulse counting mode. In some embodiments, the optical system includes a reflectron. The system may feature a lens for focusing reagent ions and product ions on the ion beam regulator, which may be an ion beam chopper, ion beam gate, ion beam modulator, Bradbury-Nielsen gate, or these Any combination of the following.

In addition, in some embodiments, the system features an optical system disposed relative to the chamber and the mass spectrometer module. The optical system includes at least one quadrupole lens such that the flow of reagent ions and product ions is directed to the ion beam regulator. In some embodiments, the mass spectrometer module defines an approximately linear axis through the flight zone. The approximately linear axis may be approximately parallel to the second axis passing through the flight region (eg, Uthoff trajectory).

In some embodiments, the system includes a mass filter disposed relative to the microwave energy source and the chamber to selectively allow a subset of reagent ions to enter the chamber. The mass filter may be a quadrupole mass filter. The system may feature an analysis module that receives data from the mass spectrometer module to interpret data of the mass spectrum including values of mass and / or peak intensities of product ions and reagent ions. The analysis module can be used to detect and / or identify defects in the mass spectrometry system. The analysis module may be based on multivariate statistical analysis.

In some embodiments, the system features a multivariate statistical analysis module that identifies components of a sample based on mass spectra generated by the mass spectrometer module. The system may include a control module operable to detect or identify a fault in the system based on the operating parameters of the system and in communication with the system. The control module may change the value of the operating parameter based in part on the identification or detection of the fault.

The system can include a control module in communication with the system to change a value of an input parameter of the system based on an operating parameter of the system. In some embodiments, the system includes a set of electrodes disposed relative to the chamber to create a field to facilitate interaction between product ions and the sample and to allow product ions and reagent ions to pass through the outlet orifice of the chamber. . Such a system may feature a control module in communication with the set of electrodes to determine a value of a field in the chamber based on the operating parameters of the system. The operating parameters of the system include the composition of the sample, the pressure in the chamber, the rate at which product or reagent ions pass through the chamber, the flow rate of sample or reagent ions into the chamber, the energy of the product or reagent ions, the product ions, the reagent ions. , Or the chemical composition of the sample, or any combination thereof. The control module is also operable to change the input parameter of the set of electrodes based in part on the operating parameter.

In another aspect, the invention is directed to a system. The system includes a microwave or high frequency RF energy source for ionizing particles of gaseous reagents by microwave or RF energy to form one or more reagent ions. The system includes a chamber that includes an inlet port that allows a sample to be input to interact with product ions from a microwave or RF energy source to form one or more product ions. The system also includes a time-of-flight mass spectrometer positioned relative to the exit orifice of the chamber to produce a spectrum that includes the mass values of the product and reagent ions based on the amount of time each of the product and reagent ions traverse the mass spectrometer. Contains modules

In some embodiments, the time-of-flight mass spectrometer module includes a flight zone through which product and reagent ions pass. The flight zone defines the path length. In addition, the time-of-flight mass spectrometer module includes an ion beam conditioner for controlling the flow of product ions or reagent ions into the flight region, and optics disposed in the flight region to increase the length of the path through which product and reagent ions travel. It includes a system. The analyzer module also includes a collector for receiving product ions and reagent ions from the flight zone.

In another aspect, the invention relates to a method for processing signals of a time-of-flight mass spectrometer. The signals are based on one or more reagent ions generated by providing microwave or RF energy to the gaseous reagent, and also based on one or more generated ions generated by interacting the reagent ions with a fluid sample of the electromechanical. The method includes establishing a first ion stream comprising reagent ions and product ions, and modifying the first ion stream to produce a second ion stream in accordance with a particular flow pattern. The method also includes accepting a second ion flow at the detector, and determining the mass spectrum from the data communicated by the detector in accordance with a maximum likelihood statistical algorithm. Mass spectra include data indicative of the mass and / or peak intensities of reagent ions and product ions.

In some embodiments, the second ion flow is a pulsed flow. The pulsed flow may be based on a specific flow pattern generated according to the pseudo random number binary arrangement.

In another aspect, the invention relates to a method. The method includes supplying a gaseous reagent to the plasma region, and providing microwave or high frequency RF energy to the gaseous reagent in the plasma region to form one or more reagent ions. The method also includes interacting the reagent ions with the gas sample to produce one or more product ions. The method includes directing product and reagent ions along the trajectory in the flight region of the time-of-flight mass spectrometer module. The method also includes determining, by a mass spectrometer module, values of mass and / or peak intensity of product ions and reagent ions.

One aspect of the invention relates to a system for measuring the mass of one or more reagent ions and one or more product ions. Reagent ions are produced by providing microwave or RF energy to a gaseous reagent. Product ions are produced by interacting one or more reagent ions with a fluid sample in an electromechanical. The system includes a set of quadrupole lenses disposed with respect to the ion outlet orifice of the drift tube assembly to receive a first ion flow comprising reagent ions and product ions. The set of lenses receives product ions and reagent ions through the outlet orifice and produces a second ion flow towards the ion beam regulator. The system also includes an ion beam conditioner operable to selectively allow the second ion flow to be delivered to the flight region of the time-of-flight mass spectrometer.

In another aspect, the invention is directed to a system. The system includes means for ionizing particles of gaseous reagents by microwave or high frequency RF energy to form one or more reagent ions. The system also includes means for including the electromechanical to interact with the sample with the reagent ions to form one or more product ions. The system also includes means for determining values of respective peak intensities and / or masses of the product ions and the reagent ions based on the amount of time that the product ions and the reagent ions traverse a certain distance.

In another aspect, the present invention relates to a system for measuring the mass of one or more reagent ions and one or more product ions. Reagent ions are produced by providing microwave or RF energy to a gaseous reagent. Product ions are produced by interacting reagent ions with a fluid sample in an electromechanical system. The system includes means for establishing a first ion flow comprising reagent ions and product ions. The system also includes means for adjusting the first ion flow in accordance with a particular interruption pattern to produce a second ion flow. The system also includes means for generating a mass spectrum from data communicated from the detection means. The data corresponds to the second ion flow.

In another aspect, the present invention relates to a system for measuring the mass of one or more reagent ions and one or more product ions. Reagent ions are produced by providing microwave or RF energy to a gaseous reagent. Product ions are produced by interacting reagent ions with a fluid sample in an electromechanical system. The system includes optical means for receiving a first ion stream comprising reagent ions and product ions. The optical means also produces a second flow of ions towards the conditioning means. The system also includes its adjusting means for selectively controlling the second ion flow to the mass spectrometer.

In another aspect, the invention relates to a method. The method includes introducing a sample gas. The method also includes supplying a gaseous reagent to the plasma region and providing microwave or high frequency RF energy to the gaseous reagent in the plasma region to form one or more reagent ions. The method also includes interacting one or more reagent ions with a sample gas to produce one or more product ions and directing the product and reagent ions to a quadrupole or time-of-flight mass spectrometer module. The method includes determining, by a mass spectrometer module, values of mass or peak intensity of product ions and reagent ions.

In another aspect, the invention is directed to a system. The system includes a microwave or high frequency RF energy source for ionizing particles of gaseous reagents by microwave or RF energy to form one or more reagent ions. The system includes a source for facilitating the analysis of a sample gas comprising one or more volatile organic compounds at least in small concentrations. The system also includes a chamber having an inlet port that allows sample gas to be input to interact with reagent ions from a microwave or high frequency RF energy source to form one or more product ions. The chamber has an electromechanical produced in the chamber. The system also includes a quadrupole or time-of-flight mass spectrometer module disposed relative to the exit orifice of the chamber to collect the product ions and reagent ions to facilitate determination of the mass or peak intensity values of the product and reagent ions. .

In another aspect, the present invention is directed to a mass spectrometry system comprising means for introducing a sample gas comprising at least one volatile organic compound at least in small concentrations. The system includes means for generating one or more reagent ions from the gaseous reagent by providing microwave or high frequency RF energy to the gaseous reagent source. The system includes means for interacting the sample gas with reagent ions to form one or more product ions. The system also includes means for directing the product ions and reagent ions to the mass spectrometer module to determine at least one of the peak intensity or mass of the product ions and reagent ions or to identify volatile organic compounds of the sample gas.

Further features relate to the foregoing aspects. For example, the sample gas includes one or more volatile organic compounds at least in small concentrations. The micro concentration may be about 1 pptv to about 1 ppbv. The micro concentration may be about 1 ppbv to about 1 ppmv.

The method may also include connecting the gas sample inlet port to a confined space. The method may also include positioning the gas sample inlet port in a non-enclosed space. The gas sample inlet port may be connected to the container. In some embodiments, the gas sample inlet port is connected to an exhaust pipe of an automobile or aircraft. The gas sample inlet port may be connected to the headspace above the food or beverage product, for example to determine the content of the food or beverage product.

In some embodiments, the method includes positioning the gas sample inlet port close to the human mouth to introduce exhalation into the gas sample inlet port. The method includes positioning a gas sample inlet port close to the solid sample material being released as a gas or vapor. In some embodiments, the gas sample inlet port is connected to a gas source.

The quadrupole or time-of-flight mass spectrometer module may facilitate determination of at least one of the peak intensity or mass of the volatile organic compound of the gas sample, or the identity of the volatile gas compound. Volatile organic compounds that can be measured, detected, and / or identified at small concentrations include dioxin compounds, furan compounds, chlorophenols, naphthalenes, benzenes, ethylbenzenes, xylenes, non-methane organic compounds, secondary organic aerosols, copper Elemental compounds, chemical inorganic agents, electric field gases, fire accelerators, VOC species released by body fluids or through the activity of fungal species (eg fungal poisons), or any combination thereof. In some embodiments, volatile organic compounds include anthropogenic or biogenic volatile organic compounds. In some embodiments, the sample gas includes an inorganic gas or gaseous species (eg, hydrogen sulfide).

The details of one or more examples are set forth in the accompanying drawings and the description below. Additional features, aspects, and advantages of the invention will be apparent from the description, drawings, and claims.

It provides a robust mass spectrometry system that can provide continuous and real time field analysis. It also provides a system that can reliably determine the presence and identification of a VOC in a particular sample, including a small amount of VOC.

1 is a plan view showing the components of a system implementing the present invention.
2 is a cross-sectional view of a gas phase reagent supply assembly for a mass spectrometry system.
3 is a flow chart of a method for generating reagent ions.
4 is a flowchart illustrating a mass spectrometry method of practicing the present invention.
5 is a cross-sectional view of a quadrupole mass spectrometer system of the present invention.
FIG. 6 is an enlarged view of the drift chamber assembly shown in FIG. 5.
7 is a plan view of a time-of-flight mass spectrometer module embodying the present invention.

1 is a plan view illustrating components of a system 100 embodying the present invention. System 100 includes a gaseous reagent source 104 and a plasma generator 108. The microwave / RF plasma generator 108 may generate plasma using microwave energy (microwave plasma) or high frequency RF energy (RF plasma). RF energy may be supplied by a capacitively coupled high frequency RF energy source (not shown). The gaseous reagent (not shown) from the gaseous reagent source 104 interacts with the plasma in the plasma region 112 to form the required or specific reagent ions, which reagent ions are subjected to specific applications for the system 100. And may be one or more of a number of different species. In some embodiments, the plasma region 112 and the microwave / RF plasma generator 108 form portions of the same assembly (not shown) such that the gaseous reagents interact with the plasma within the assembly. In some embodiments, the plasma region 112 is disposed in a glass tube.

Plasma region 112 is in fluid communication with electrically isolated orifice plate electrode 120 mounted within flange 116. Insulators (not shown) are disposed therebetween to provide electrical isolation between the flange 116 and the orifice plate electrode 120. A potential is applied to the orifice plate electrode 120 to increase the potential of the plasma, whereby one or more reagent ions pass through the opening 122 defined by the flange 116 and the orifice plate electrode 120 to form a drift outer chamber. And into chemical ionization / drift region 136 in 124. The chemical ionization / drift region 136 is maintained at a lower potential than the orifice plate electrode 120. Sample source 128 is in fluid communication with chemical ionization / drift region 136 to provide a sample fluid (eg, sample gas) to system 100. Sample gas flows into an inlet port (not shown) to flow through the surface of drift outer chamber 124 (not shown) and into chemical ionization / drift region 136. The inlet port can be positioned below the orifice plate electrode 120 located centrally in the flange 116 to allow reagent ions to mix with the components of the sample gas in the chemical ionization / drift region 136. Other configurations for introducing reagent ions and sample gas into the chemical ionization / drift region 136 exist and are within the scope of the present invention. For example, the inlet port may be connected to the flange 116 to create a "showerhead" effect when the sample gas flows through a fluid path (not shown) located radially relative to the opening 122.

Drift assembly 126 includes a chemical ionization / drift region 136 and a pumped drift outer chamber 124. The pumped drift outer chamber 124 effectively receives the chemical ionization / drift region 136. The chemical ionization / drift region 136 may be defined by a series of electrodes and insulating plates (with an intermediate O-ring seal (not shown)), each of which is centered on a series of electrodes and insulating plates. A passage penetrating is arranged. Chemical ionization / drift region 136 is described in more detail with reference to FIGS. 5 and 6. Chemical ionization / drift region 136 facilitates interaction (eg, chemical reaction) between the sample and the reagent ions. The interaction between the sample and the reagent ions forms one or more product ions. Typically, reagent ions are much more than the components of the sample gas, and reagent ions can be monitored in the product ion stream after product ions are produced. Chemical ionization / drift region 136 generally includes an electromechanical (not shown) to facilitate interaction between sample and reagent ions when the sample and reagent ions are mixed within chemical ionization / drift region 136. . Electromechanical of the chemical ionization / drift region 136 also directs reagent ions and product ions toward the exit orifice 138.

Ions passing through the chemical orifice / drift region 136 through the outlet orifice 138 are focused onto the outlet orifice 144 defined by the flange 140. The outlet orifice 144 allows ions to leave the drift outer chamber 124. Ions are focused onto the exit orifice 144 by the lens assembly 142. In some embodiments, lens assembly 142 includes a focus opening. Some embodiments employ a three-element Einzel lens for the lens assembly 142. The lens assembly 142 directs the ions toward the mass spectrometer module 148 according to certain flow parameters such as, for example, the flow rate, velocity or momentum of the ions. Lens assembly 142 may be used to optimize the number of ions passing through exit orifice 144. In some embodiments, system 100 does not include a lens assembly.

The mass spectrometer module 148 determines the mass and amount of reagent ions and product ions, for example by collecting ions. The mass spectrometer module 148 generates and / or analyzes mass spectral results indicative of reagent ions and product ions passing through the outlet orifice 144. Mass spectra associated with product ions can be used to determine the presence, amount, volume, concentration, or identity of a sample provided by sample source 128. The system 100 is calibrated and / or error checked using the measurement of reagent ions. The mass spectrometer module 148 may be a quadrupole mass spectrometer or a time-of-flight mass spectrometer.

System 100 also includes a control module 152. The control module 152 receives data about a parameter or operating state of the system 100. Based on this data, the control module 152 may determine or set input values or input operating parameters for the components of the system. For example, the control module 152 may include a gaseous reagent source 104, a plasma generator 108, a plasma region 112, an orifice plate electrode 120, a chemical ionization / drift region 136, a lens assembly 142. Data may be received from the exit orifice electrode 144, or the mass spectrometer module 148. The control module 152 may set input values for each of these components in response to the collected data, for example, when the system 100 initiates or responds to data received regarding an operating parameter.

In some embodiments, the control module 152 automatically updates input values for the operating parameter in response to data received regarding the operating parameter. For example, if operating parameters relating to pressure or electromechanical within the chemical ionization / drift region 136 deviate from a specific or desired value for these parameters, the control module 152 may control the parameters to those parameters. The sample source 128 may be adjusted to set the pressure of the electrodes (not shown) or the chemical ionization / drift region 136 to produce the electromechanical until it corresponds to input values or correction values. Other operating parameters may include the velocity or energy of the reagent ions or product ions in the system 100, the flow rate of the fluid sample into the chemical ionization / drift region 136, the flow rate of the reagent ions into the chemical ionization / drift region 136. , The composition of the sample, the relative concentration of sample and reagent ions, or the relative concentration of reagent ions and product ions. In some embodiments, control module 152 monitors a number of operating parameters of system 100.

In some embodiments, control module 152 uses a plasma metrology process to receive and / or update parameters of system 100. The plasma metrology process may, for example, monitor the emission spectrum from the plasma region 112. Based on the emission spectrum, the control module 152 determines the value of operating parameters (eg, plasma parameters) in the plasma region 112, eg, the intensity of a particular emission wavelength, wherein the parameter is specified. If away from the value or the desired value, the control module 152 may adjust these plasma parameters until the plasma parameters correspond to optimal values for those parameters. If the control module 152 cannot obtain an optimal state or parameter, it can detect and / or register a fault condition.

In some embodiments, a mass filter (not shown) may be located between the microwave / RF plasma region 112 and the chemical ionization / drift region 136. The mass filter can be used to selectively allow reagent ions to be transferred into the chemical ionization / drift region 136. In some embodiments, the mass filter is a quadrupole mass filter.

System 100 includes one or more ports (not shown) connected to one or more pumps (not shown) to establish pressure values across system 100. For example, the pressure values in the microwave / RF plasma region 112, chemical ionization / drift region 136, pumped drift outer chamber 124, and mass spectrometer module 148 are maintained by one or more pumps.

2 is a cross-sectional view of a gaseous reagent supply assembly 200 for a mass spectrometry system (eg, system 100 of FIG. 1). The assembly 200 is configured to provide a consistent or stable flow rate or flow of water vapor to an energy source, for example to the plasma generator 108 of FIG. 1. The water vapor provided by the assembly 200 may be ionized by microwave or RF plasma and includes one or more reagent molecules, sometimes called gaseous reagents. Assembly 200 includes a reservoir 202 for receiving a fluid source. The reservoir 202 may be constructed of stainless steel or other suitable metal.

In some embodiments, reservoir 202 contains water or pure water to produce water vapor. As shown, the reservoir 202 includes five ports. Port 204 is connectable to a tube or channel for introducing fluid into the reservoir (eg, for stopping water or fluid supply). Port 206 is connectable to a tube or channel for delivering or passing gaseous reagents to a mass spectrometry system. Port 208 is connectable to a tube or channel for obtaining measurements regarding the fluid in reservoir 202. For example, port 208 can be connected to a capacitor pressure gauge to determine headspace pressure in reservoir 208. In some embodiments, port 208 is not used. Port 216 is connectable to a tube or channel (eg, to connect to a water level indicator) for measuring the amount of fluid in reservoir 202. Port 218 is connectable to a conduit or channel for draining or emptying reservoir 202. Each of the ports 208, 216 is optional and, in some embodiments, is not included in the system 200 or used for mass spectrometry operation. In some embodiments, each of the ports 204, 206, 208, 216, 218 is connectable to tubes of 0.25 inches in diameter (about 0.635 centimeters). Other sizes of tubes or channels may be connected to the port, and the tubes or channels do not have to be the same size.

In some embodiments, the reservoir 202 is heated to a particular elevated temperature using a heater jacket 214 surrounding the reservoir 202. In some embodiments, the control module 152 of FIG. 1 is connected to a thermocouple 212. The temperature of the reservoir 202 (and fluid therein) may be an operating parameter that is maintained, regulated and regulated by the control module 152 in response to the operation of the mass spectrometry system. By such control, the user can maintain the gaseous pressure of the headspace 213 on the liquid surface 210 to a specific or desired value.

Assembly 200 also includes tubing 222 in fluid communication with mass flow controller 224. The mass flow controller 224 can determine the amount of gaseous reagent that flows into the plasma region 230 through the piping 226, where reagent ions are applied by applying microwave or RF energy to the gaseous reagent in the region 230. Is generated. In some embodiments, mass flow controller 224 may be a heated mass flow controller with separate electronic components (not shown) located remotely from assembly 200.

Other types of flow controllers may be used in conjunction with or instead of the mass flow controller 224. As shown, assembly 200 includes a gauge or monitor 228 to indicate pressure values in plasma region 230. The gauge may be a capacitive pressure gauge. In some embodiments, the control module 152 of FIG. 1 is connected to a gauge or monitor 228 and the pressure in the plasma region 230 is maintained, regulated and regulated by the control module 152. Parameter. In some embodiments, the gauge or monitor 228 is not included in the assembly 200.

In some embodiments, tubing 222 and tubing 226 are formed of stainless steel and define an outer diameter of about 0.25 inches (about 0.635 centimeters). The tube 229 electrically separates the body of the assembly 200 from the plasma region 230. In some embodiments, tube 229 is formed of polytetrafluoroethylene (PTFE) and defines an outer diameter of about 0.25 inches (about 0.635 centimeters). The pressure in the plasma reaction zone 230 is about 1-5 torr (about 100-700 pascals) during the mass spectrometry operation. Pressure in assembly 200 is maintained by a pump (not shown) outside assembly 200. For example, using a pump connected to the drift outer chamber 124 of FIG. 1 (and then connected to the chemical ionization / drift region 136), the pressure of the assembly 200 is communicated through fluid communication with the assembly 200. It can be established. The chemical ionization region 136 of FIG. 1 may be in fluid communication with the assembly 200 through the opening 122 and the plasma region / tube 112.

In some embodiments, port 220 is used to improve reagent ion production by mixing gaseous reagents with other gases during application of microwave or RF energy. For example, the mixed gas may be argon, nitrogen, or an argon / nitrogen mixture. In some embodiments, a gas or gas mixture (eg NO or O ₂ ) used in reagent ion generation is introduced through port 220, and reservoir 202 is piped by a valve (not shown). Fluidly separated from 222.

3 is a flow chart 300 of a method for generating reagent ions. In step 305, gaseous reagents are supplied. For example, gaseous reagents may be supplied according to the system 200 shown in FIG. 2 to provide a relatively consistent or stable gaseous reagent flow. The gaseous reagent may be pure water vapor or water vapor mixed with a plasma mixed gas such as argon or nitrogen or mixtures thereof. In some embodiments, the gaseous reagent comprises reagent species such as nitrous oxide (NO) or divalent oxygen (O ₂ ).

In step 310, energy is provided to the gaseous reagent. In some embodiments, the energy is microwave radiation used to form an ionized microwave plasma. In some embodiments, the energy is high frequency RF power, which is used to form an RF plasma of the type generated by, for example, a capacitively coupled RF energy source. Microwave energy generally refers to energy (eg, radioactive energy) generated by electromagnetic waves having frequency values above about 800 MHz and below about 300 GHz. High frequency RF energy generally refers to energy generated by electromagnetic waves (eg, radioactive energy) having a frequency value of greater than about 400 kHz and less than about 800 MHz. Specifically, RF energy may be provided within a frequency value specified by an Industrial, Scientific, and Medical (ISM) radio center band frequency.

The energy applied in step 310 energizes or excites molecules at the flow rate of the gaseous reagent to produce reagent ions. The molecules in the gaseous reagent stream are ionized by the plasma. For example, when steam is used as the gaseous reagent, hydronium ions are produced through a multistage reaction.

- 반응식 1

Scheme 1

- 반응식 2

Scheme 2

Scheme 1 shows the interaction between freely charged ionized water molecules and free electrons (e ⁻ ) from an ionized plasma that interact with water molecules (H ₂ O) to form a second free electron. In Scheme 2, positively charged water molecules interact with neutral water molecules to form hydronium ions and hydroxyl groups. Hydronium ions may be reagent ions for subsequent interaction with components of the fluid sample.

Both microwave and high frequency RF plasmas are preferred because they present an efficient means of generating sufficient sources of ions and electrons to generate reagent ion species, such as hydronium ions. In addition, microwave and high frequency RF plasmas are relatively clean, with little or no internal sputtering often associated with a hollow cathode / glow discharge plasma source in which the electrodes are in direct contact with the plasma. The "electrodeless" nature of microwave and high frequency RF plasma sources means that the effects of drift and instability associated with electrode corrosion are reduced. In addition, microwave and high frequency RF plasma sources can provide relatively constant high levels of reagent ions.

In some embodiments, the method of FIG. 3 includes an additional step (not shown) that includes measuring pressures of microwave and high frequency RF plasma. The plasma pressure value may be a control parameter for the mass spectrometry system (eg, controllable by the control module 152 of FIG. 1). In addition, the plasma pressure may be used to determine an appropriate supply of gaseous reagents (eg, from assembly 200).

4 is a flowchart illustrating a mass spectrometry method 400 for practicing the present invention. Step 405 is to provide a gaseous reagent, and step 410 is to provide microwave or RF energy to the gaseous reagent to generate reagent ions, for example, as described above with respect to FIG. 3. The reagent ions are then subjected to chemical ionization / Head to the drift region.

In step 415, a fluid sample (eg, a gas containing molecules of one or more volatile organic compounds) interacts with reagent ions. Interaction occurs between the fluid sample and the reagent ions by mixing the fluid sample and the reagent ions. For example, the fluid sample may be supplied to the flow of reagent ions through the inlet line and pass through the drift outer chamber into the chemical ionization / drift region. The pressure drop between the sample feed and the chemical ionization / drift region can facilitate the fluid flow to return the fluid sample into the chemical ionization / drift region. The chemical ionization / drift region includes an electromechanical that facilitates the movement of reagent ions within it and facilitates collisions between reagent ions and components of the fluid sample. The collision between reagent ions and the components of the fluid sample results in a chemical reaction that ionizes the particles of the fluid sample. An example of a chemical reaction with respect to sample species (R) and hydronium ions of a constituent molecule having a quantum affinity greater than that of water is as follows.

- 반응식 3

Scheme 3

Chemical reactions for hydronium ions and species (R) are low energy and / or soft ionization interactions. For example, when compared to higher energy ionization processes such as electron impact ionization, the integrity of the sample molecules is not significantly altered and the molecular fragmentation of the sample is reduced or minimized. In addition, species of samples having a quantum affinity less than the affinity of water are not ionized by collisions with hydronium atoms and thus are not detected during mass spectrometry. Examples of such species are common constituents of air, including divalent nitrogen, divalent oxygen, argon, carbon dioxide, methane. In general, these components of air exhibit high intensity spectral peaks in the mass spectrum obtained based on a substantial portion of the components of the air of the sample with respect to the components present in the sample in small amounts. High intensity spectral peaks can obscure nearby low intensity peaks or increase the difficulty in distinguishing low intensity peaks from high intensity peaks. Thus, the selective nature of this chemical ionization technique can improve the ability to distinguish spectral peaks due to low intensity / small level species in the sample.

In step 420, reagent ions and product ions exit the chemical ionization / drift region through the lens or outlet orifice assembly and into the collector region of the mass spectrometer. In some embodiments, the reagent ions and product ions leave the chemical ionization / drift region by an electromechanical established in the chemical ionization / drift region. Reagent ions and product ions may pass through the orifice and through the lens assembly through the orifice at the end of the chemical ionization / drift region into the mass spectrometer module. The lens assembly may feature a focus opening or may feature a three element Einzel lens. In some embodiments, the ion extraction orifice is disposed in the flange. The potential can be applied to the lens assembly and the ion extraction orifice such that an electric field is created that allows reagent ions and product ions to pass through the ion extraction orifice. In general, the mass spectrometer module operates at a relatively high vacuum to ensure that molecular flow conditions drive the effective operation of the mass spectrometer and its component parts.

The mass spectrometer module may comprise a quadrupole mass spectrometer or a time-of-flight mass spectrometer. For either type of mass spectrometer, reagent ions and product ions are directed to the collector region of the mass spectrometer. Ions collide with the collector in the collector region and as a result the current is amplified in the mass spectrometer (eg using a combination of electron multiplier and preamplifier). Based on the input from the collector, the mass spectrometer accumulates data on reagent ions and product ions and generates a signal spectrum that indicates the amount and mass values (or mass to charge ratio) of the collected ions.

Step 425 is to determine the mass and amount of reagent ions and product ions, for example, based on the mass spectra generated. Well-resolved peaks in the mass spectrum can be used to determine the exact mass or mass-to-charge ratio of both reagent and product ions. In addition, the exact location of these peaks facilitates component identification of the fluid sample by comparison with known ions or molecules with mass values determined from spectral peaks or signal peaks. In some embodiments, an analysis module can be used to display the signal spectrum and / or determine the presence and location of peaks in the spectrum.

5 is a cross-sectional view of a quadrupole mass spectrometer system 500 embodying the present invention. System 500 includes a reagent ion source 504 coupled to chemical ionization / drift region 508. The reagent ion source 504 of the system 500 is based on a microwave energy source that includes a magnetron 512 with a stub aerial 514 disposed through the opening 516 of the resonant cavity 520. In some embodiments, reagent ion source 504 may be based on a high frequency energy source, such as an RF energy source. Reagent ion source 504 also includes a tube 524 that passes through resonant cavity 520 through opening 528. The tube 524 also passes through two microwave chokes 532 disposed on the outer surface 536 of the resonant cavity 520. The microwave choke 532 reduces the amount of microwave energy exiting the resonant cavity 520 or the tube 524 and reduces the microwave energy extending to other components of the system 500. The tube 524 may be formed of a silica material such as silica or quartz. In some embodiments, the tube 524 may be formed of sapphire. End 540 of tube 524 may be connected to a corresponding end (not shown) of a gaseous reagent source (not shown) for providing gaseous reagent to reagent ion source 504. For example, the end 532 may be connected to the tube 229 of the gas phase reagent supply system 300 shown in FIG. 2.

의 거리에 위치한다. 보다 구체적으로, 관(524)은 공진 공동(520)으로부터 관(524)으로 전달되는 공진 에너지를 최대화하도록 공진 공동(520)의 안티 노드(anti-node)에 위치한다.In some embodiments, the tube 524 has an outer diameter of about 6 millimeters. Resonant cavity 520 defines a length 1 along the y axis. The length is approximately equal to or corresponding to the total one wavelength λ of the lowest order resonant mode of the resonant cavity 520. The tube 524 is approximately along the y axis from the top 544 of the resonant cavity 520.

Is located in the street of. More specifically, the tube 524 is located at an anti-node of the resonant cavity 520 to maximize the resonant energy transferred from the resonant cavity 520 to the tube 524.

In some embodiments, magnetron 512 is a 900 watt magnetron with stub antenna 514 that provides microwave power to resonant cavity 520. Power is radiated and transmitted to the tube 524 by electromagnetic waves with frequency values in the microspectral of the resonant cavity 520. As a result of the resonance energy in the cavity 520 interacting with the gaseous reagent inside the tube 524, plasma is generated inside the tube 524. The gaseous reagent is input into the tube 524 through an end 540 connected to a gaseous reagent source. Due to the pressure drop between the tube 524 and the chemical ionization / drift chamber 508, the gaseous reagent source provides a flow of gaseous reagents or directs them into the tube 524, for example along the x axis. Continuous flow of gaseous reagents ensures that the microwave plasma is maintained inside the tube 524 to generate one or more reagent ions, for example, as described above.

일 수 있다. In some embodiments, resonant cavity 520 consists of an aluminum extrusion plated with silver having a closed end (eg, top 544 and bottom 548 of cavity 520). In some embodiments, the microwave choke 532 is cylindrical having a centerline parallel to the x axis, coaxial with the x axis, or collinear with the x axis. The microwave choke 532 may be formed of stainless steel or aluminum. In some embodiments, channel 533 is disposed within one or both of microwave chokes 532. The length of channel 533 is approximately along the y axis

Can be.

The second end 552 of the tube 524 terminates at the surface 557 of the orifice plate 556 that is maintained in the flange 560 and is attached to the chemical ionization / drift region 508 (see FIG. 6). . Reagent ions travel from tube 524 through orifice plate 556 and into chemical ionization / drift region 508. Chemical ionization / drift region 508 is defined in part by annular electrodes 564 spaced along the x axis through the center of drift outer chamber 562. A potential is applied to each of the electrodes 564 to create an electromechanical. In some embodiments, the electromechanical has a linear system gradient along the x axis. The value of the positive potential applied to each electrode is reduced along the positive direction of the x-axis to produce a linear system gradient towards the axial direction. Nonlinear gradients may also be used. The electrodes 564 are electrically separated from each other by annular insulating components 568 disposed between them. The electric field facilitates the interaction between reagent ions from the reagent ion source 504 (eg, the tube 524) and the sample introduced at the chemical ionization / drift chamber port 566.

The drift outer chamber 562 also includes a pumping port 576 connected to the pumping system 580. The drift outer chamber 562 has a port 571 with a tubular connector (not shown) for sample lead (not shown) and for fluid communication between the entire pressure gauge 572 and a second gauge (not shown). And electrical feedthrough ports (not shown). In some embodiments, the pumping system 580 includes a turbomolecular pump with a diaphragm backing pump (not shown). Pumping system 580 establishes the required pressure within drift outer chamber 562 and chemical ionization / drift region 508. The pressure in chemical ionization / drift region 508 can be monitored by the entire pressure gauge 572 and the pressure in the drift outer chamber 562 can be monitored by a second gauge (not shown). The data provided by these gauges is supplied as input to a control module (not shown), for example for a system diagnostic process.

The chemical ionization / drift region 508 and the drift outer chamber 562 include a flange 584 that is connected to the corresponding flange 588 of the mass spectrometer 592 via a double-sided flange 586. The mass spectrometer 592 shown in the system 500 is a quadrupole mass spectrometer. The mass analyzer 592 includes an analyzer probe 594 and is in fluid communication with the pumping system 596. Pumping system 596 may, for example, facilitate mass determination of reagent ions and product ions and reduce the negative effects of such ion mass measurements resulting from interactions with the surrounding components of the mass spectrometer. Establish pressure in

Ions transferred from chemical ionization / drift region 508 to mass spectrometer 592 are directed to mass spectrometer probe 594 by ion extraction electrode 582. In some embodiments, an ion optical assembly (not shown) with an ion extraction electrode 582 can be used to increase the number of reagent ions and product ions delivered to the mass spectrometer 592. For example, a focus aperture or a three element Einzel lens can be used. Analyzer probe 594 may be an electrically biased quadrupole mass spectrometer or mass filter. The quadrupole mass spectrometer comprises, for example, four parallel metal rods parallel to the x-axis and arranged as square vertices. Opposite pairs of rods are electrically connected to create two electrically coupled dipoles. The voltage with the positive DC voltage component or the first RF energy may be applied to the rods of the first dipole, and the voltage with the negative DC voltage component or the second RF energy may be applied to the rods of the second dipole. have. Ions on the stable trajectory through the mass filter generally travel between the rods in a direction parallel to the rods (eg, parallel to the central axis of the square).

RF and / or DC energy applied to the analyzer probe 594 creates a mass-selective oscillating field. With mass selective vibrometers, ion trajectories of a particular shape, such as oscillation shapes generally along the x axis, occur. The trajectory is specified such that ions outside a certain range do not follow the trajectory to the detector 598 while ions with values of mass to charge ratio within that specific range substantially follow the trajectory to the detector 598. Non-selective ions collide with the rods and are not collected by the detector 598. In some embodiments, the mass selective system varies with the value of energy applied to the quadrupole rods, eg, potential, DC energy, or RF energy. The bandwidth of the mass values can be selected by the particular field strength or flow rate. The analyzer probe 594 can also search the mass range by varying the mass selective system.

In some embodiments, analyzer probe 594 includes a series of three linear coaxial quadrupoles called triple-filter quadrupole mass analyzers. In such embodiments, the first and third embodiments of the triple filter are relatively short (eg, 1 inch or 2.54 centimeters) "RF only" filters, which are applied to themselves by a second or main filter. Carries the RF voltage component that is transmitted. These "RF only" prefilters and post filters function as ion lenses and focus ions into and out of the mass filter assembly. The use of pre-filters and post-filters in this way is intended to improve ion permeation through the filter assembly, in particular by increasing the number of permeated ions and exceeding a larger mass (eg, greater than about 80 atomic mass units). Mass) to improve ion permeation. In addition, prefilters and postfilters improve the filter's massive sensitivity performance and mass resolution. Ions that successfully pass through the triple filter assembly are collected by detector 598. In some embodiments, detector 598 is an electron multiplier detector. The electron multiplier detector amplifies the electrical signal generated by ion bombardment with the inlet or front of the detector (not shown).

FIG. 6 is an enlarged view of the chemical ionization / drift region 508 shown in FIG. 5. Chemical ionization / drift region 508 includes a chemical ionization / drift chamber 620 mountable on an ion extraction electrode 612 that defines an extraction orifice 616. Reagent ions pass through the extraction office 616 as they move from the plasma region 608 into the chemical ionization / drift region 508. Ion extraction electrode 612 may be in fluid communication with an energy source (not shown). Ions pass through extraction orifice 616 under the influence of an electromechanical generated by the potential applied to ion extraction electrode 612. Ion extraction electrode 612 is connected to flange 504 by one or more screws (not shown) having a ceramic insert or an insert formed of another insulating material. These screws and inserts pass through an insulating (eg, ceramic or PEEK) collar 614 to further isolate the ion extraction electrode 612 from the flange 604. In some embodiments, the value of the potential applied on the extraction electrode 612 is a chemical ionization / drift chamber of the chemical ionization / drift region 508 along the centerline A where the reagent ions are approximately parallel to the x-axis. 520) affects the average energy of the reagent ions. In addition, the size and / or shape of the extraction orifice 616 determines the amount of flow of reagent ions into the chemical ionization / drift chamber 620.

Ions pass through extraction orifice 616 of extraction electrode 612 and into chemical ionization / drift chamber 620 along approximately centerline A (eg, axial or parallel to the x-axis). Electromechanical is generated in the drift region 620 by a potential applied to each of the drift end plate electrode 625 and one or more plate electrodes 624 (also called an electrode stack). The electrodes may be formed of a metallic material or other conductive material. In some embodiments, each of the plate electrodes 624 and the drift end plate electrodes 625 has an annular shape with the center opirises 630, 633 aligned with the center line A. The diameter of the central orifice 630 of each plate electrode is about 10 millimeters. The diameter of the central orifice 633 of the drift end plate electrode is about 1 to 2 millimeters. Other diameters and shapes (eg non-circular) are also within the scope of the present invention. Plate electrodes 624 and drift end plate electrodes 625 are physically separated and electrically separated by one or more insulating collars 628. In some embodiments, insulating collar 628 has an annular shape with center orifice 631 aligned with center line A. The diameter of the central orifice 631 of the insulating collar 628 may be about 20 millimeters. Other diameters and shapes are also within the scope of the present scaffold. Suitable materials for the insulating collar 628 include polymer materials such as collars formed of PEEK ^TM sold by Victrex plc of Lancashire, UK, or static losses sold by Quadrant Engineering Plastic Products of Reading, Pennsylvania, USA. static dissipative) plastic. A zero-ring (not shown) is located in the annular groove on either side of each of the insulating collars 628. The zero ring facilitates hermetic sealing at the interface between the insulating collar and the plate electrode 624 or the drift end plate electrode 625. In some embodiments, these 0-rings may be formed of VITON® fluoroelastomers sold by Du Pont Performance Elastomers, Wilmington, Delaware.

Extraction electrode 612, plate electrodes 624, and drift end plate electrode 625 cooperate to create an electromechanical within chemical ionization / drift chamber 620. In some embodiments, the electromechanical has a linear system gradient along the x axis. The electromechanical may also be non-linear, for example, based on differences between the potentials applied to the extraction electrode 612, each of the plate electrodes 624, and the drift end plate electrode 625. The electromechanical controls the reagent ions and facilitates the interaction between the components of the fluid sample and the reagent ions.

In some embodiments, each of the plate electrodes 624 along the centerline A in a direction increasing along the x-axis to facilitate the flow of reagent and product ions within the chemical ionization / drift chamber 620. A reduced potential is applied to the drift end plate electrode 625. Sample gas is, for example, as shown in FIG. 1 through a port in the drift outer chamber (eg, port 571 in FIG. 5) and then through a port 632 on the insulating collar 628 side. It is supplied to a chemical ionization / drift chamber 620 from a sample source (not shown). Similar ports on the other insulating collar 628 side may be in fluid communication with gauge 572 on port 571 of FIG. 5 to facilitate pressure measurement within chemical ionization / drift chamber 620. In some embodiments, the sample source consists of a mass flow controller that is used to control the flow of a fluid sample input to the chemical ionization / drift chamber 620. The sample gas is advanced along the centerline A in the direction of increasing along the x axis to interact with the reagent ions. The plate electrodes 624 and the drift end plate electrode 625 are fixed to the extraction electrode 612, which extracts the plate electrodes 624 and the drift end plate electrode 625 into the chemical ionization / drift chamber 620. Support within).

In some embodiments, a control module (not shown) is ion extracting electrode 612, each of plate electrodes 624, and a drift end plate to provide a potential to each of electrodes 612, 624, 625. Is connected to electrode 625. In addition, the control module monitors other parameters within the chemical ionization / drift chamber 620 such as system gradient, pressure, or detected ionic strength. If the value for a particular monitoring parameter deviates from a predetermined threshold, the control module determines the value for the potential applied to the ion extraction electrode 612, each of the plate electrodes 624, and the drift end plate electrode 625. Can be reset or adjusted.

In some embodiments, the control module, via a feedback loop, responds to a change in the parameters of the chemical ionization / drift chamber 620 to the ion extraction electrode 612, each of the plate electrodes 624, and the drift end plate. The potential of the electrode 625 is automatically changed. For example, the control module may establish, as an initial state or mode, a pressure and field gradient that defines an optimal e / n (eg, charge density) setting for a given sample monitoring requirement. In some embodiments, the control module can monitor the parameters of the chemical ionization / drift chamber 620 and maintain optimal e / n levels through real-time adjustment of the electric field gradient and / or pressure. In some embodiments, the control module, for example, distinguishes two isoic compounds using different e / n levels, based on chemical ionization / Drift chamber 620 system gradients and / or pressure levels may be changed. In some embodiments, the electric field gradient established by ion extraction electrode 612, each of plate electrodes 624, and drift end plate electrode 625 is linear along the x-axis (or along center line A). to be. In some embodiments, the field gradient is nonlinear. Another parameter that can be monitored by the control module and related to the electric field, pressure, and / or e / n levels in the chemical ionization / drift chamber 620 is the ratio of product ions to reagent ions.

The drift outer chamber 562 includes a fixed flange 636 fixed to the corresponding flange 640 of the mass spectrometer 644 with a double-sided flange 648 disposed between these two flanges. Ion extraction electrode 652 defining extraction orifice 656 is secured to flange 648 by, for example, one or more insulating screws 660. An insulating collar 658 (formed of ceramic, for example) electrically separates the ion extraction electrode 652 from the double-sided flange 648. The metal plate 659 shields the insulating collar 658 and reduces the buildup of surface charges that may interfere with ion optics in the region 657 between the chemical ionization / drift chamber 620 and the mass spectrometer 644. A potential is applied to the ion extraction electrode 652 to create a system that directs reagent ions and product ions from the chemical ionization / drift chamber 620 to the mass spectrometer 644. The mass analyzer 644 includes an analyzer probe 664 having one or more holes 668 to facilitate vacuum pumping and / or withdrawal of the mass analyzer 644 and analyzer probe 664. Analyzer probe 664 is approximately aligned with center line A, and ions may be input to analyzer probe 664 along center line A through focus electrode 676. Analyzer probe 664 is coupled to an analysis module that generates and / or displays mass spectra based on reagent ions and product ions collected by a detector (not shown) coupled to analyzer probe 664. In some embodiments, reagent ions reaching the mass spectrometer 644, for example, using additional ion optics (not shown) in the region between the chemical ionization / drift chamber 620 and the mass spectrometer 644. And optimize the level of generated ions. Ion optics may take the form of a focus aperture of a three element Einzel lens.

7 is a plan view of a time-of-flight mass spectrometer system 700 embodying the present invention. System 700 includes an ion source 704 for supplying ions to system 700. Ion source 704 may supply product ions and reagent ions, for example, from chemical ionization / drift chamber 620 in chemical ionization / drift region 508. Ions travel through the ion flow from the ion source 704 into the time-of-flight mass spectrometer 708. Ions may be input to the time-of-flight mass spectrometer 708 via an ion extraction orifice (not shown) of an ion extraction electrode (not shown) that is electrically isolated from the time-of-flight mass spectrometer 708. The potential can be applied to the ion extraction electrode to generate an electromechanical for controlling the ions in the time-of-flight mass spectrometer 708.

The time-of-flight mass spectrometer 708 is in fluid communication with a pumping system 712 that establishes pressure in the flight chamber 708. The ions are directed towards the ion optical assembly 716, which includes a set of ion lenses 720. One or more potentials are applied to the ion lenses 720 to provide an electromechanical device for defining and controlling the shape of the ion beam. For example, ion lenses 720 constrain the possible trajectories of ion flow and thereby focus ion flow or increase ion flow rate through less volume. In addition, ion lenses 720 may reduce variability in the velocity spectrum or dispersion of ions. In some embodiments, ion lenses 720 are electrostatic lenses, such as quadrupole lenses, to which one or more DC potentials are applied. Ion lenses 720 create a focusing system that interacts with the ion flow to minimize spatial variability in the direction of the ion flow (eg, along trajectory 728). Optical assembly 716 can optimize the characteristics of the ion beam or flow, for example, to increase the rate of ion flow rate, momentum, or rate of ion flow rate. By this improvement of the beam characteristics, the resolution of the mass spectrum and the peak detection of the mass spectrum can be improved. Peaks in the mass spectrum indicate the identity or amount of particular ions having a particular mass value. By improving the resolution and spectral peaks of the mass spectrum, the discrimination between peaks and spectral or signal noise can be improved.

The ions leave the optical assembly 716 in a concentrated flow towards the ion beam conditioner 724. The ion beam regulator 724 may be a chopper assembly that interrupts or regulates the flow of ions along the trajectory 728 through the flight region 732. In some embodiments, ion beam regulator 724 is coupled to a drive system (not shown), eg, to a digital electronic control module that controls the parameters of ion beam regulator 724. These parameters can be controlled according to specific interruptions or flow patterns. These parameters include the positive and negative voltages applied to the alternating wires of the ion beam regulator, such that ion scattering occurs when the voltages are applied and thus tracks 728 when no potential is applied. The ions thus flow (or as pulses) without interruption. In some embodiments, the magnitude of the positive and negative voltages applied can be adjusted for optimal performance. In some embodiments, the drive system controls the parameters of the ion beam conditioner 724 according to a particular pattern, eg, the pattern in which the ion beam conditioner gate is repeatedly opened and closed over a certain time. The drive system can also control the parameters of the ion beam conditioner 724 in accordance with a pseudo or non-specific pattern. In some embodiments, the drive system is based on a pseudo random number binary arrangement that can generate a pulsed flow of ions along the trajectory 728. In some embodiments, ion beam conditioner 724 is an ion gate that can be rapidly switched to produce a pulsed ion flow, for example according to a particular flow pattern. One example of a suitable ion gate is a Bradbury-Nielsen gate.

Ions travel along the trajectory 728 and toward the second optical system 736 in the decreasing direction of the x axis. Optical system 736 may be a reflectron (also referred to herein as part number 736) that affects the direction of trajectory 728 by reflecting ions and / or changes the direction of the trajectory, where the trajectory The path of 728a is symmetrical with the path of trajectory 728, with the axis of symmetry passing through the center of reflectron 736. In some embodiments, reflectron 736 includes a set of electrostatic lenses (not shown) for reflecting and / or rerouting ion flow along the reflected trajectory 728a. In some embodiments, reflectron 736 consists of two sections of resistive glass tubes bonded to each other. A grid (not shown) is located on the front surface 730 of the reflectron 736 and the second grid 738 is located between the two bonded tube sections. A fixed potential can be applied to the grid at the front side 730, in the grid between the two sections of the tube, and at the rear side 734 of the reflectron 736. By this arrangement, an electrode gradient can be established in the tube for ion reflection. The ions follow the reflected trajectory 728a to the detector 740 after leaving the optical system.

The optical system 736 can be used to increase the path length 1 through which ions travel in the flight region 732, for example, to increase the resolution of the signal peaks of the obtained mass spectrum. The path length 1 may have a known or determined value, for example, based on the sum of the respective lengths of the trajectory 728 and the reflection trajectory 728a. The amount of time needed for ions to cross path length 1 can be used to determine the mass or mass to charge ratio for reagent ions or product ions. For example, the amount of time required to traverse the path length 1 may be determined by the kinetic energy or velocity of the ions in the flight chamber 708 after acceleration under the influence of the electromechanical produced by the optical system 716. Indicates. The time spent by the ions crossing the path length l can be used in conjunction with Lorentz force and Newton's second law to determine mass or mass to charge ratio. The optical system 736 can also be used to correct for variations in the kinetic energy of reagent ions and product ions. Ions with relatively high kinetic energy move more into the optical system (along the decreasing x-axis direction) than ions with relatively low kinetic energy. This phenomenon is sometimes referred to as passing or reflecton passing. Positioning the detector 740 at or near the focal point of the locus 728 or the reflection locus 728a reduces the effect of energy distribution on the mass spectrum.

Ions traveling through the flight zone 732 from different pulses of the ion beam conditioner 724 can be mixed in the flight zone 732, so that the signal is received by the detector 740 or to the detector 740. Signal convolution is caused in the mass spectrum produced by it. The detector 740 is generally located at or near the energy focus, such that the energy of the same mass but leaving the optical system 736 is collected at about the same time by different detectors of different ions. In some embodiments, detector 740 is a stacked microchannel plate detector. Detector 740 operates in a pulse counting mode. The pulse counting mode allows the collection of these individual ions when the individual ions reach the detector after passing through the flight zone 732. In some embodiments, detector 740 is used with a signal discriminator, amplifier, and / or time-to-digital converter (TDC).

If the ion beam conditioner 724 employs pseudo random number binary array pulsed, the signal obtained from the ions collected by the detector 740 can be deconvolved using signal processing techniques such as statistical signal processing techniques. have. Statistical signal processing techniques provide information about a signal or spectrum based on statistical analysis of the convolved signal or spectrum. One example of a suitable signal processing technique for deconvolution of the acquired signal is maximum likelihood signal processing.

의 형태로 각 이벤트에 대하여 기입될 수 있다. 각 이벤트에 대하여, y(x_i) 합치 함수는 정규화 확률 밀도 함수인

로 변환될 수 있다. 확률 밀도 함수(P_i)는 x_i의 관찰 값에서 계산될 수 있다. 우도 함수

는

이도록 개별 확률 밀도들의 적(product)이고, 다양한 파라미터들(a_i)의 최대 우도 값들은 그 파라미터들에 대하여 우도 함수

를 최소화함으로써 얻을 수 있다. Maximum likelihood signal processing typically performs statistical calculations based on measured events. For example, i is consistent from one to N of the independent variable (x _i) and the N for the set of events, the data (x _i, y _i) measurement for measuring the dependent variable (y _i) function (fitting function). The match function includes m parameters ai, where i is 1 to m. The match function is

It can be written for each event in the form of. For each event, the y (x _i ) match function is a normalized probability density function

Can be converted to A probability density function (P _i) may be calculated from the observed values of x _i. Likelihood function

Is

Is the product of the individual probability densities, and the maximum likelihood values of the various parameters a _i are the likelihood functions for those parameters.

By minimizing

In some embodiments, the time-of-flight mass spectrometer 700 operates using pseudo random number binary array pulsedness of the ion beam conditioner 724 to produce a convolved signal or spectrum. The convolved signal or spectrum is then deconvolved using maximum likelihood signal processing. When used in this mode, ion beam conditioner 724 allows ions to pass for about 50% of the total available time and allow about 50% of the total available ions to pass through the flight zone 732. The "high duty cycle" operation of these time-of-flight mass spectrometers offers performance advantages in terms of improved signal-to-noise, improved sensitivity, and wider dynamic range. In some embodiments, the time-of-flight mass spectrometer 700 includes a single pulse in which all ions from a single pulse of the ion beam conditioner 724 are collected by the detector 740 before a subsequent pulse of the ion beam conditioner is triggered. It works in mode.

In addition to the benefits provided by the high duty cycle operation of the time-of-flight mass spectrometer 700, maximum likelihood signal processing also provides additional performance improvements over other signal deconvolution methods. Maximum likelihood signal processing treats signal noise as Poisson noise rather than Gaussian noise. In addition, the maximum likelihood signal processing may refer to the actual instrument response function, for example, to the actual ion beam regulator pulse shape rather than the ideal instrument response function. This performance improvement facilitates increased signal resolution as well as further improvements in signal-to-noise and dynamic range.

In some embodiments, maximum likelihood signal processing is performed by a data analysis module (not shown). In addition, the data analysis module can be used to identify species of the mass spectrum based, for example, on the basis of lookup tables or univariate or multivariate probability methods. In some embodiments, the data analysis module can be based on multivariate statistical analysis. Suitable multivariate statistical analyzes include, for example, principal component analysis or partial least squares discriminant analysis (PLS-DA) using Hotelling or DModX analysis. In some embodiments, the data analysis module is used to interpret the sample data to determine if the sample is associated with a particular population. In some embodiments, the data analysis module monitors the diagnostic output of the system to determine if a fault has occurred in a system, such as system 100 of FIG. 1, for example.

There are many applications for the mass spectrometry systems and techniques described herein. Specifically, the volatile organic compound can be detected by a minute amount or concentration. The increased sensitivity and ability to detect and identify microvolatile organic compounds in real time provides a variety of applications for the systems and methods described herein. Specific applications include sampling of gases (eg, environmental atmosphere, gas from a confined space, gas from a gas source, gas released from a solid sample or container, or gas from a headspace on a food or beverage product). . The sampled gas is then introduced to the gas sample inlet port to interact with the reagent ions to form product ions. Specific applications and detection of volatile organic compounds relate to how and where gas sample inlet ports are located.

In some embodiments, the gas sample inlet port includes specific application features that tailor the gas sample inlet port to the needs of the art. For example, in the field of medical diagnostics, a gas sample inlet port may be connected to a face mask that covers a person's nose and mouth. The gas sample inlet port or face mask may also include a bacterial filter. In the field of sampling from an environment containing particles, for example, a particle filter may be integrated into the sample line or gas sample inlet port. In applications where the vapor phase sample contains condensable species, the heater may be integrated into the system (eg, sample line) to heat the sample line to a specific temperature.

Examples of sample gas collectors are containers, containers, or vacuum based products that include an outlet port that allows gas to be delivered into a gas sample inlet port. The gas collector can collect the gas in the environment in which it is found and store it for later analysis, in which case the collector is relatively incapable of gas penetration. In some embodiments, the gas collector includes an outlet port for supplying into the gas sample inlet port and into the drift chamber for real time detection and / or monitoring.

Various applications for the mass spectrometry systems and methods described below are within the spirit and scope of the present invention. One category of applications for the mass spectrometry techniques described above is the measurement of the micro level concentration of volatile organic compounds in air, including the environmental atmosphere. The environmental atmosphere can be sampled from an enclosed space or a non-enclosed space (eg, by placing the gas sample inlet port close to the environmental atmosphere).

Volatile organic compounds can be monitored in urban areas for detection of vehicle emissions or pollutants in cities and towns and / or close to industrial sites. These are sometimes referred to as anthropogenic VOCs. For example, industrial sites may include chemical plants, waste incinerators, steel and / or cement production facilities. Industrial facilities can emit VOCs such as dioxin surrogate (and dioxin based), furan (and furan based), chlorophenol, naphthalene, benzene, toluene, ethylene, xylene (collectively referred to as BTEX) species. . In addition, VOCs or municipal hazardous air pollutants may, in response to certain programs such as VOC initiators or non-methane organic compound initiators, be regulated by regulatory agencies such as the United States Environmental Protection Agency or other Ministry for the Environment (MfE). Is identified.

In some embodiments, placing the gas sample inlet port near a waste incinerator or chimney is useful for real time monitoring and regulation (eg, real time feedback) to reduce emissions. This real-time monitoring is also useful for optimizing the combustion process and for verifying the scrubber's stated efficiency.

In some embodiments, the gas sample inlet port is located in a confined space to monitor the VOC content in the air in the confined space. Examples of enclosed spaces are in buildings, in vehicles, and aircraft cabins. The gas may be sampled from a workspace location (eg, a clean room in a semiconductor manufacturing facility or factory) to confirm adherence to environmental regulations (eg, occupational safety and health regulations). In addition, the gas sample inlet port may be used to control ambient air, to investigate “building syndrome”, to detect deterioration of building materials, including leaky buildings, and in consumer products (eg, coatings and materials within buildings). Can be used for real-time monitoring and detection of air conditioning and filtration systems in buildings.

The mass spectrometry described herein can be used to monitor and detect VOCs emitted by forests and / or plants, eg, in non-urban, rural, or remote locations. Typically, this type of VOC is known as a biogenic VOC. In some embodiments, the gas is sampled from the headspace of the container containing the soil sample (eg, to test the VOC of the soil sample taken from or around the contaminated area). Mass spectrometry techniques can be used to monitor, detect, and analyze gaseous emissions from landfills, livestock farm areas (including intensive animal sample cycle operations), and / or water systems.

In non-enclosed spaces, gas sample inlet ports can be located downstream from the vehicle or aircraft engine exhaust to monitor and / or quantify the VOC content of emissions or other gases of interest, including hydrogen sulfide (H ₂ O). The techniques described herein are also applicable to the study of atmospheric chemistry and / or atmospheric composition by placing a gas sample inlet port to obtain atmospheric gas. These gases are analyzed to study and evaluate the photooxidation process and / or other mechanisms that lead to the formation of secondary organic aerosols that may include isotope compounds.

The techniques described herein can also be applied to the food and beverage industry. For example, the headspace on a food or beverage product contains gases that can be analyzed using mass spectrometry. The headspace may be in a closed space (eg inside a sealed container) or in a non-closed space.

Examples of food and beverage applications include the aromas of various foods such as coffee, olive oil, dairy products, meat products (including poultry and pork), fish products, herbs and condiments, beer, wine, and other alcoholic beverages. And / or monitoring, identification, and grouping of aromas. The fragrances of the gas can be determined and / or identified based on the VOC components that contribute to the different fragrances. Chemical ionization reactions and / or quantum transfer reaction mass spectrometry can be used to monitor food decay and / or spoilage, for example, through analysis of VOCs resulting from bacterial activity in food. Mass spectrometry herein can be used to help determine product safety and shelf life, as well as to determine the freshness of food (eg, bread), and to provide quality assurance and quality control. Mass spectrometry techniques can be used to monitor the process of food production, including mixing, blending, roasting, and cooking, and to determine whether a particular batch of food is inappropriate for distribution or consumption.

Within the food and beverage industry, mass spectrometry can be used to detect contaminants in food from food packaging (eg, contaminants resulting from residual solvents or plastic food packaging). The mass spectrometry techniques herein can be applied to test water soluble and fat soluble preservatives and / or other food additives used in a variety of foods.

Chemical ionization reactions and / or quantum transfer reaction mass spectrometers can also be applied as an instrument for diagnosis or prediction in the medical and healthcare fields. For example, the gas sample inlet port may be located close to the human mouth to collect human breath and provide it to the mass spectrometry system. VOC of respiration may indicate the presence of a particular disease or physical condition within a patient. There are several applications of respiratory analysis involving VOCs. For example, respiration may be analyzed by detecting specific alkanes or benzene derivatives to screen for various types of cancer, such as, for example, lung cancer. In addition, for other conditions such as pulmonary tuberculosis, diabetes, fungal infections (e.g., in bone marrow patients), schizophrenia, and / or manic depression, breathing may be analyzed based on the VOC species and amount in their patients' breaths. Can be.

In addition, the mass spectrometry described herein can be used to monitor kidney or other kidney function. Respiration of a human suffering from cystic fibrosis may include certain VOCs in the presence of a bacterial infection and may diagnose the infection. In some embodiments, human breathing includes a specific VOC that indicates organ transplant rejection. In addition, human breathing may include microenhancing drugs that can be detected by the foregoing assays. In addition, respiratory analysis and detection of VOCs can be used to tailor diets and diets for athletes and patients. By performing VOC analysis on human respiration using the mass spectrometer described herein, it is possible to evaluate and monitor metabolism and diagnose thyroid problems.

Chemical ionization reactions and / or quantum transfer reaction mass spectrometry are applied in the fields of security, biosecurity, forensic investigation and criminal research. For example, the systems and methods described herein may be used to monitor and detect the location of explosives, chemical weapon agents (CWAs), and / or battlefield gases, fire accelerators (on fire investigations), and bodies. Can be used. In addition, the gas sample inlet port may be positioned to collect human respiration and detect exposure to CWA or electrical field gas. Mass spectrometry can be used to detect and analyze specific VOCs that are characteristic of different body fluids (eg, evidence collected at a crime scene). The concepts described herein are also applicable to the detection and detection of drugs and / or drugs of abuse through respiratory analysis or by connecting gas sample inlet ports to containers suspected of containing drugs of abuse. More generally, the gas sample inlet port may be connected to a shipping container or package to detect a VOC characterized by a material or material (eg, anthrax or spores) that poses a biosecurity threat.

In addition, the techniques described above can be used to monitor crops for agricultural pests and pathogen contamination as evidenced by the presence of VOCs. For example, a gas sample inlet port may be located near the grain to detect the presence of fungal toxins (fungal poisons) in the grain. Chemical ionization reactions and / or quantum transfer reaction mass spectrometry can also be used to detect fungi or insects of crops after harvesting (eg, before distribution to food and beverage production companies).

Chemical ionization reactions and / or quantum transfer reaction mass spectrometry applications also exist in the cosmetic, toiletry, and consumer pharmaceutical industries, such as, for example, analysis and testing of products during the product development phase. In addition, mass spectrometry can be employed during the production process to detect any defects or defective products prior to release.

Examples of applications from the cosmetics, toiletries, and consumer pharmaceutical industries are perfume research and development based on the identification of VOC components contributing to certain flavors (eg, perfumes, antiperspirants, odor removers). The concepts described herein are also applicable to the development and testing of toiletries and consumer products (eg, to monitor VOC content and detect VOC levels during test use or in laboratory environments). Such products include mouthwashes, toothpastes, soaps, sterile ointments, creams, deodorants, antiperspirants. Oral hygiene products can also be analyzed and monitored using respiratory assays. Like the food and beverage industry, chemical ionization reactions and / or quantum transfer reaction mass spectrometry, including evaluation of product stability and / or shelf life, are common quality control and / or quality assurance programs for cosmetics, toiletries and consumer pharmaceutical products. Can be used for

Further applications exist for chemical ionization reactions and / or quantum transfer reaction mass spectrometry. For example, the described concepts can be used for process monitoring and control in the biopharmaceutical industry to monitor and identify VOCs generated during the fermentation process. Some regulatory bodies (eg, ASTM International) have announced goals for improving the quality, safety and efficiency of biopharmaceutical products. Positioning gas sample inlet ports to collect samples for on-line analysis during the manufacturing process further develops this regulatory goal.

In some embodiments, mass spectrometry can be used for biological research to detect at low concentrations of VOCs associated with plant leaf injury and defense mechanisms. In some embodiments, the gas sample inlet port is positioned to collect the sample from a gas source such as, for example, a hydrocarbon column. The VOC content of the feed gas is determined according to the methods described above. Hydrocarbon pillars may represent oil and / or gas deposits, and mass spectrometry techniques herein may be used for petroleum exploration. In addition, chemical ionization reactions and / or quantum transition reaction mass spectrometry can be used in the analysis and optimization of catalyst performance in the automotive industry. In this application, the gas sample inlet port is positioned to collect both pre-catalyst and post-catalyst gas species, for example for comparison. Other applications will be apparent to those skilled in the art and are within the spirit and scope of the present invention.

In some embodiments, an analyzer that incorporates the principles of the present invention is used as a component of an electronic nose system. In some embodiments, the electronic nose system also includes an analysis module for analyzing the signals output by the analyzer. The electronic nose system can be used to analyze gases and gases, including gases and gases in the headspace on a solid or liquid material comprising a plurality of components. The analysis module may analyze the signals output by the analyzer and identify specific components in the sample. In addition, the analysis module performs a global fingerprint analysis of the existing species (ie, obtains a chemical signature), which is compared with fingerprints from other substances of previously stored information.

In some embodiments, the analysis module is particularly useful for processing multiple sample parameters (e.g., many VOC component peaks that characterize a given odor and aroma) to characterize and compare the samples, for example. A computer processor implementing a variable analysis algorithm, pattern recognition algorithm, or neural network algorithm. For example, multivariate analysis techniques are useful for the observation and analysis of more than one statistical variable and can reduce data from complex fingerprints to allow simple comparisons. By using this approach, similar scents and scents can be grouped and outliers identified and highlighted.

Electronic nose systems have often been used to analyze the overall fingerprint of VOCs released by food and beverages, which often consist of large amounts of components (eg, a plurality of different VOC species). For example, odors are composed of molecules, each of a specific size and shape. Each of these molecules has receptors of size and shape corresponding to the human nose. The analyzer can be used to uniquely fingerprint many different molecules in an odor sample. Further applications for electronic nose systems include detection of disease-specific odors for medical diagnosis, and detection of pollutants and gas leaks for environmental protection. In some embodiments, the electronic nose system includes additional sensors (eg, metal oxide semiconductor (MOS), conductive polymer (CP), quartz crystal trace balance and field effect transistors) that output signals analyzed by the analysis module. One or more gas sensors (including MOSFETs).

While the invention has been described with reference to specific embodiments, it will be understood by those skilled in the art that various changes may be made in form and detail without departing from the spirit and scope of the invention as defined by the claims.

Claims (79)

Introducing a sample gas,
Supplying a gaseous reagent to the plasma region;
Providing microwave or high frequency RF energy to the vapor phase reagent in the plasma region to form one or more reagent ions;
Interacting the one or more reagent ions with the sample gas to produce one or more product ions,
Directing the one or more product ions and the one or more reagent ions to a quadrupole or time-of-flight mass spectrometer module;
Determining by the mass spectrometer module a value for at least one of the mass or peak intensity of each of the one or more product ions and the one or more reagent ions
Including, the method. The method of claim 1,
And the sample gas comprises one or more volatile organic compounds at least in micro concentrations. The method of claim 1,
Wherein the introducing comprises connecting a gas sample inlet port to a confined space. The method of claim 1,
Wherein the introducing step locates the gas sample inlet port in a non-enclosed space. The method of claim 1,
Wherein the introducing comprises connecting a gas sample inlet port to a container. The method of claim 1,
Wherein the introducing comprises connecting a gas sample inlet port downward from an exhaust pipe of an automobile or aircraft. The method of claim 1,
Wherein the introducing comprises connecting a gas sample inlet port to a head-space above a food or beverage product. The method of claim 1,
Wherein the introducing step includes positioning a gas sample inlet port close to a human mouth to collect exhalation. The method of claim 1,
Wherein the introducing comprises positioning a gas sample inlet port close to a gas or a solid sample material that emits a gas. The method of claim 1,
Wherein the introducing comprises connecting a gas sample inlet port to a gas source. A microwave or high frequency RF energy source for ionizing particles of the gaseous reagent by microwave or RF energy to form one or more reagent ions,
A source for facilitating the analysis of a sample gas comprising at least one volatile organic compound at least in small concentrations,
A chamber in which the sample gas is input to form one or more product ions to interact with the one or more reagent ions from the microwave or high frequency RF energy source, the chamber in which an electromechanical is generated;
An outlet orifice of the chamber to collect the one or more product ions and the one or more reagent ions to facilitate determination of at least one of the mass or peak intensity of each of the one or more product ions and the one or more reagent ions. Quadrupole or time-of-flight mass spectrometer module
Including, the system. The method of claim 11,
The quadrupole or time-of-flight mass spectrometer module facilitates determination of at least one of the mass or peak intensity of the one or more volatile organic compounds of the gas sample. The method of claim 11,
The quadrupole or time-of-flight mass spectrometer module facilitates determination of the identity of the one or more volatile organic compounds in the gas sample. The method of claim 11,
The at least one volatile organic compound is a dioxin compound, a furan compound, chlorophenol, naphthalene, benzene, toluene, ethylbenzene, xylene, non-methane organic compound, secondary organic aerosol, isotope compound, chemical inorganic agent, electric field gas, A system comprising a fire accelerator, a volatile organic compound characterized by the presence of body fluids and fungi and mycotoxins, or any combination thereof. The method of claim 11,
Wherein said at least one volatile organic compound comprises anthropogenic or biogenic volatile organic compound. As a mass spectrometry system,
Means for introducing a sample gas comprising at least one volatile organic compound at least in micro concentrations,
Means for generating one or more reagent ions from a gaseous reagent source by providing microwave or high frequency RF energy to the gaseous reagent,
Means for interacting the sample gas with the one or more reagent ions to form one or more product ions,
Mass spectrometer of the one or more product ions and the one or more reagent ions to determine the value of at least one of the respective mass or peak intensity of the one or more product ions and the one or more reagent ions or to identify the one or more volatile organic compounds Means for directing
Including, mass spectrometry system. A microwave or high frequency RF energy source for ionizing particles of the gaseous reagent by microwave or RF energy to form one or more reagent ions,
A chamber in which an electromechanical is generated therein, the chamber comprising an inlet port for inputting a sample from the microwave or high frequency RF energy source to interact with the one or more reagent ions to form one or more product ions;
Quadruple disposed with respect to the exit orifice of the chamber to collect the one or more product ions and the one or more reagent ions to facilitate determination of the value of the respective mass or peak intensity of the one or more product ions and the one or more reagent ions. Pole mass spectrometer module
Including, the system. The method of claim 17,
The microwave energy source comprises a microwave plasma generator. The method of claim 17,
The high frequency RF energy source comprises a capacitively coupled RF plasma generator. The method of claim 17,
Wherein said one or more reagent ions comprise hydronium ions, oxygen ions, or nitrous oxide ions. The method of claim 17,
Wherein the sample comprises one or more volatile organic compounds. The method of claim 17,
A set of electrodes disposed relative to the chamber to facilitate interaction between the one or more reagent ions and the sample and to produce an electromechanical for passing the one or more product ions and the one or more reagent ions through an outlet orifice of the chamber Further comprising, the system. The method of claim 22,
The set of electrodes is disposed radially with respect to the axis of the chamber,
The electromechanical directs the one or more product ions and the one or more reagent ions to approximately axial directions. The method of claim 22,
And a control module in communication with the set of electrodes and operable to determine a value of an electromechanical in the chamber based on an operating parameter of the system. The method of claim 17,
Further comprising a mass flow controller, a capillary tube, or a leak valve to determine the amount of sample input to the chamber. The method of claim 17,
And a mass filter disposed relative to the chamber with the microwave or high frequency RF energy source such that the reagent ions can be selectively introduced into the chamber. The method of claim 26,
The mass filter is a quadrupole mass filter. The method of claim 17,
And a multivariate analysis module in communication with the system and operable to analyze data from the quadrupole mass spectrometer module. The method of claim 17,
The microwave energy source,
Microwave generator,
Resonator,
A tube disposed in the resonator and communicating with the chamber;
A gaseous reagent source, the chamber, or one or more chokes through which the tube passes to reduce the amount of microwave energy therein, both the gaseous reagent source and the chamber. The method of claim 17,
And a control module in communication with the system and operable to change an input parameter of the system based in part on the operating parameter of the system. 31. The method of claim 30,
The operating parameter of the system is
The composition of the sample, the pressure of the chamber, the rate of the one or more product ions or the one or more reagent ions passing through the chamber, the flow rate of the sample or reagent ions into the chamber, the one or more product ions or the one or more reagent ions At least one of the energy of, the chemical composition of reagent ions and product ions, or any combination thereof. 31. The method of claim 30,
And the control module is operable to change an input parameter of the set of electrodes generating an electromechanical within the chamber based in part on the operating parameter. The method of claim 17,
And a control module in communication with the system and operable to identify or detect a deficiency in the operating parameters of the system. The method of claim 33, wherein
And the control module is operable to change a value of the operating parameter based in part on the detection or identification of the defect. The method of claim 17,
A control module in communication with the system to monitor the system, the control module operable to set or adjust a value of an operating parameter of the system in response to the monitoring;
Wherein the control module is based on a multivariate statistical analysis algorithm. The method of claim 17,
Disposed relative to the chamber to define an orifice through which reagent ions or product ions pass toward the quadrupole mass spectrometer module and to specify energy values of the reagent ions or product ions for collection by the quadrupole mass spectrometer module Further comprising an operable extraction electrode. The method of claim 17,
And a lens assembly disposed relative to the chamber to focus the reagent ions and the product ions on an extraction orifice that facilitates passage of reagent ions and product ions directed to the mass spectrometer module. A method for generating one or more reagent ions for a quantum transition reaction mass spectrometer or a chemical ion reaction mass spectrometer,
Supplying a gaseous reagent,
Providing microwave energy to the gaseous reagent to produce one or more reagent ions
Including, the method. The method of claim 38,
Directing the one or more reagent ions to a region for interacting with the constituents of the sample to form product ions. The method of claim 38,
Wherein the one or more reagent ions are generated by a microwave plasma. The method of claim 38,
The gaseous reagent comprises water vapor, oxygen, or nitrous oxide,
Wherein said at least one reagent ion comprises a hydronium ion, an oxygen ion, or a nitrous oxide ion. The method of claim 38,
Wherein the microwave energy is provided by an electromagnetic wave having a frequency greater than about 800 MHz. A method for generating one or more reagent ions for a quantum transition reaction mass spectrometer or a chemical ion reaction mass spectrometer,
Supplying a gaseous reagent,
Providing high frequency RF energy to the gaseous reagent to produce one or more reagent ions
Including, the method. The method of claim 43,
Wherein the RF energy is provided by an electromagnetic wave having a frequency of about 400 kHz to about 800 MHz. The method of claim 43,
Wherein the one or more reagent ions are generated by a capacitively coupled RF plasma. Supplying a gaseous reagent to the plasma region,
Providing microwave or high frequency RF energy to the vapor phase reagent in the plasma region to form one or more reagent ions;
Interacting the at least one reagent ion with a gas sample to produce at least one product ion;
Directing the at least one product ion and the at least one reagent ion to a collector region of a quadrupole mass spectrometer module;
Determining, by the mass spectrometer module, values of each mass or peak intensity of the one or more product ions and the one or more reagent ions.
Including, the method. As a mass spectrometry system,
Means for generating one or more reagent ions from a gaseous reagent source by providing microwave or high frequency RF energy to the gaseous reagent,
Means for interacting a sample with the one or more reagent ions to form one or more product ions,
Means for including an electromechanical to direct the one or more product ions and the one or more reagent ions to a collector region;
Means for communicating with the collector region to determine a value of the mass or peak intensity of each of the one or more product ions and the one or more reagent ions
Including, mass spectrometry system. A microwave or high frequency RF energy source for ionizing particles of the gaseous reagent by microwave or RF energy to form one or more reagent ions,
A chamber comprising an inlet port for inputting a sample to form one or more product ions to interact with the one or more gaseous reagents from the microwave or RF energy source;
A mass spectrometer module disposed relative to the outlet orifice of the chamber,
The mass spectrometer module,
A flight zone through which the one or more product ions and the one or more reagent ions pass, defining a path length,
A collector region receiving said at least one product ion and said at least one reagent ion from said flight region,
The mass value is determined based on the amount of time each of the one or more product ions and the one or more reagent ions traverses the path length. 49. The method of claim 48 wherein
The mass spectrometer module,
An ion beam regulator disposed relative to the exit orifice of the chamber to pulse the flow of the one or more product ions and the one or more reagent ions into the flight zone;
An optical system disposed in the flight zone to increase the value of the path length through which the one or more product ions and the one or more reagent ions travel
Further comprising, the system. The method of claim 49,
And the ion beam regulator regulates the flow of the one or more product ions and the one or more reagent ions by a pseudo random number binary arrangement provided from a controller. 51. The method of claim 50 wherein
The analysis module
Performing a maximum likelihood signal processing algorithm on the data received from the mass spectrometer module to determine the value of each peak intensity or mass of the one or more product ions and the one or more reagent ions. The method of claim 49,
The analysis module deconvolves data received from the mass spectrometer module to determine a value of the mass or peak intensity of each of the one or more product ions and the one or more reagent ions. The method of claim 49,
Wherein the collector region comprises a stacked microchannel plate detector or an anode detector operating in a pulse counting mode. The method of claim 49,
And the optical system comprises a reflectron. The method of claim 49,
A lens for focusing said reagent ions and said product ions onto said ion beam regulator,
And the ion beam conditioner comprises an ion beam chopper, an ion beam gate, an ion beam modulator, or any combination thereof. 49. The method of claim 48 wherein
And an optical system disposed relative to the chamber and the mass spectrometer module,
The optical system comprises at least one quadrupole lens directing a flow of the one or more product ions and the one or more reagent ions to an ion beam regulator. 49. The method of claim 48 wherein
The mass spectrometer module defines an approximately linear axis through the flight zone. The method of claim 57,
And the substantially linear axis is approximately parallel to a second axis passing through the flight zone. 49. The method of claim 48 wherein
And a mass filter disposed relative to the microwave energy source and the chamber such that the subset of the one or more reagent ions can be selectively input into the chamber. The method of claim 59,
And the mass filter comprises a quadrupole mass filter. 49. The method of claim 48 wherein
And an analysis module for receiving data from the mass spectrometer module to generate a mass spectrum comprising values of respective mass or peak intensities of the one or more product ions and the one or more reagent ions. 49. The method of claim 48 wherein
And a multivariate statistical analysis module that identifies components of the sample based on mass spectra generated by the mass spectrometer module. 49. The method of claim 48 wherein
And a control module in communication with the system, the control module operable to detect or identify a fault of the system based on an operating parameter of the system. The method of claim 63, wherein
And the control module is operable to change a value of the operating parameter based in part on the detection or identification of the defect. 49. The method of claim 48 wherein
And a control module in communication with the system, the control module operable to change a value of an input parameter of the system based on an operating parameter of the system. 49. The method of claim 48 wherein
An electrode disposed relative to the chamber to facilitate interaction between the one or more reagent ions and the sample and create a field for passing the one or more product ions and the one or more reagent ions through an outlet orifice of the chamber The system further comprises a set of. The method of claim 66, wherein
And a control module operable to determine a value of the system in the chamber based on the operating parameter of the system and in communication with the set of electrodes. The method of claim 67 wherein
The operating parameters of the system may include the composition of the sample, the pressure of the chamber, the rate of the one or more product ions or reagent ions passing through the chamber, the flow rate of the sample or reagent ions into the chamber, and the one or more productions. At least one of ions or energy of the one or more reagent ions, chemical composition of the reagent ions or product ions, or any combination thereof. The method of claim 67 wherein
The control module is operable to change an input parameter of the set of electrodes based in part on the operating parameter. A microwave or high frequency RF energy source for ionizing particles of the gaseous reagent by microwave or RF energy to form one or more reagent ions,
A chamber comprising an inlet port for inputting a sample to form one or more product ions to interact with the one or more reagent ions from the microwave or RF energy source;
The chamber to generate a spectrum comprising respective mass values of the one or more product ions and the one or more reagent ions based on the amount of time each of the one or more product ions and the one or more reagent ions traverse the mass spectrometer Time-of-flight mass spectrometer module positioned against the exit orifice
Including, the system. 71. The method of claim 70,
The time-of-flight mass spectrometer module,
A flight region in which the one or more product ions and the one or more reagent ions move and define a path length,
An ion beam conditioner that regulates the flow of the one or more product ions and the one or more reagent ions into the flight zone;
An optical system disposed in the flight zone to increase the value of the path length through which the one or more product ions and the one or more reagent ions travel;
A collector region for receiving the one or more product ions and the one or more reagent ions from the flying region
Including, the system. A method for processing signals in a time-of-flight mass spectrometer,
The signal is based on one or more reagent ions generated by providing microwave or RF energy to a gaseous reagent and on one or more generated ions generated by interacting the one or more reagent ions with a fluid sample of an electromechanical,
The method comprises:
Establishing a first ion flow comprising the one or more reagent ions and the one or more product ions,
Altering the first ion flow in accordance with a specified flow pattern to generate a second ion flow;
Receiving the second ion flow at a detector;
Determining a mass spectrum from data communicated by the detector according to a maximum likelihood statistical algorithm, the mass spectrum comprising data representative of each peak intensity or mass of the one or more reagent ions and the one or more product ions. step
Including, the method. 73. The method of claim 72,
And the second ion flow is a pulsed flow. The method of claim 73,
The pulsed flow is based on a particular flow pattern generated according to a pseudo random number binary arrangement. Supplying a gaseous reagent to the plasma region,
Providing microwave or high frequency RF energy to the vapor phase reagent in the plasma region to form one or more reagent ions;
Interacting the one or more reagent ions with a gas sample to produce one or more product ions,
Subjecting the one or more product ions and the one or more reagent ions to a trajectory in the flight region of the time-of-flight mass spectrometer module;
Determining, by the mass spectrometer module, a value of the mass or peak intensity of each of the one or more product ions and the one or more reagent ions
Including, the method. A system for measuring the mass of one or more reagent ions and one or more product ions,
The one or more reagent ions are generated by providing microwave or RF energy to a gaseous reagent and the one or more product ions are generated by interacting the one or more reagent ions with a fluid sample in an electromechanical,
The system,
A quadrupole arranged with respect to the ion outlet orifice of the drift tube assembly to receive a first ion flow comprising the one or more reagent ions and the one or more product ions through an outlet orifice and to generate a second ion flow directed to an ion beam regulator. With a set of lenses,
The ion beam regulator operable to selectively allow the second ion flow to be directed into the flight region of the time-of-flight mass spectrometer
Including, the system. Means for ionizing particles of the gaseous reagent by microwave or high frequency RF energy to form one or more reagent ions,
Means for including an electromechanical for interacting the sample with the one or more reagent ions to produce one or more product ions,
Means for determining the value of the respective mass or peak intensity of the one or more product ions and the one or more reagent ions based on the amount of time the one or more product ions and the one or more reagent ions traverse a specific distance
Including, the system. A system for measuring the mass of one or more reagent ions and one or more product ions,
The one or more reagent ions are generated by providing microwave or RF energy to a gaseous reagent and the one or more product ions are generated by interacting the one or more reagent ions with a fluid sample in an electromechanical,
The system,
Means for establishing a first ion flow comprising the one or more reagent ions and the one or more product ions,
Means for adjusting the first ion flow in accordance with a particular interruption pattern to produce a second ion flow;
Means for generating a mass spectrum from data communicated from a detector means, the data corresponding to the second ion flow
Including, mass measurement system. A system for measuring the mass of one or more reagent ions and one or more product ions,
The one or more reagent ions are generated by providing microwave or RF energy to a gaseous reagent and the one or more product ions are generated by interacting the one or more reagent ions with a fluid sample in an electromechanical,
The system,
Optical means for receiving a first ion stream comprising the one or more reagent ions and the one or more product ions and for generating a second ion stream directed to the conditioning means;
Said adjusting means for selectively controlling said second ion flow to a mass spectrometer
Including, mass measurement system.

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