WO2004092704A2 - Detection d'explosifs utilisant une spectrometrie a mobilite differentielle d'ions - Google Patents

Detection d'explosifs utilisant une spectrometrie a mobilite differentielle d'ions Download PDF

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Publication number
WO2004092704A2
WO2004092704A2 PCT/US2004/010862 US2004010862W WO2004092704A2 WO 2004092704 A2 WO2004092704 A2 WO 2004092704A2 US 2004010862 W US2004010862 W US 2004010862W WO 2004092704 A2 WO2004092704 A2 WO 2004092704A2
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Prior art keywords
filter
ion
analyte
field
dms
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PCT/US2004/010862
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English (en)
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WO2004092704A3 (fr
Inventor
Raanan A. Miller
Erkinjon G. Nazarov
David B. Wheeler
Quan Shi
John A. Wright
Gary A. Eiceman
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Sionex Corporation
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Priority claimed from US10/462,206 external-priority patent/US7005632B2/en
Application filed by Sionex Corporation filed Critical Sionex Corporation
Publication of WO2004092704A2 publication Critical patent/WO2004092704A2/fr
Publication of WO2004092704A3 publication Critical patent/WO2004092704A3/fr

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
    • G01N27/62—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating the ionisation of gases, e.g. aerosols; by investigating electric discharges, e.g. emission of cathode
    • G01N27/622—Ion mobility spectrometry
    • G01N27/624—Differential mobility spectrometry [DMS]; Field asymmetric-waveform ion mobility spectrometry [FAIMS]
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/22—Fuels, explosives

Definitions

  • the present invention relates generally to identification of unknown constituents of a sample by their ion mobility characteristics in an electric field, and more particularly to devices and methods that analyze compounds via high field asymmetric waveform ion mobility spectrometry.
  • Taggant options include addition of volatile chemicals, radioisotopes and the like. In countries participating under international commercial air security conventions, one of several volatile chemicals can be used to mark plastic explosives for detection. The United States has officially designated 2,3-dimethyl-2,3-dinitro-n- butane (C 6 Hj 2 N 2 O ), commonly referred to as DMNB, as a detection taggant for plastic explosives.
  • DMNB 2,3-dimethyl-2,3-dinitro-n- butane
  • Mass spectrometers are generally recognized as being one of the most accurate type of detectors for compound identification, given that they can generate a fingerprint pattern for even fragment ions.
  • mass spectrometers are quite expensive and large and are relatively difficult to deploy in the field. Mass spectrometers also suffer from other shortcomings such as the need to operate at low pressures, resulting in complex support systems. These systems also require a highly trained user to tend to operations and interpret results.
  • Ion analysis is based on the recognition that ion species have different ion mobility characteristics under different electric field conditions at elevated pressure conditions including atmospheric pressure.
  • Practices of the concept include time-of-flight Ion Mobility Spectrometry (IMS) and differential mobility spectrometry (DMS), the latter also sometimes referred to as field asymmetric waveform ion mobility spectrometry (FAIMS).
  • IMS time-of-flight Ion Mobility Spectrometry
  • DMS differential mobility spectrometry
  • FAMS field asymmetric waveform ion mobility spectrometry
  • a propelling DC field gradient and a counter gas flow are set and an ionized sample is released into the field which flows to a collector electrode.
  • Ion species are identified based on the DC field strength and time of flight of the ions to the collector.
  • the ion mobility is constant when the electric field is weak.
  • DMS systems identify ion species by mobility behavior in a compensated high asymmetric RF field, where ions flow in a carrier gas and are shifted in their path by a high-low varying electric field.
  • the conventional DMS operates with a selected Vrf and species detections are correlated with a preset, or scanned, DC compensation voltage (V c ) applied to the RF field.
  • V c DC compensation voltage
  • Species are identified based upon correlation of Vrf and V c with historical detected data. The amount of compensation depends upon species characteristics and the selected compensated field conditions.
  • a typical DMS device includes a pair of opposed filter electrodes defining an analytical gap between them in a flow path (also known as a drift tube). Ions flow into the analytical gap.
  • the asymmetric RF field (sometimes referred to as a filter field, a dispersion field or a separation field) is generated between the electrodes transverse to the carrier gas/ ion flow in the gap.
  • Field strength, E varies as the applied RF voltage, Vrf (sometimes referred to as dispersion or separation voltage) and size of the gap between the electrodes.
  • Vrf sometimes referred to as dispersion or separation voltage
  • Such systems can operate at atmospheric pressure.
  • Ions are displaced transversely by the RF field, with a given species being displaced a characteristic amount toward the electrodes per cycle.
  • the DC compensation voltage (V c ) is applied to the electrodes along with the V r f to compensate the displacement of a particular species. Now the applied compensation will offset transverse displacement generated by the applied Vr f for that particular ion species. The result is zero or near- zero net transverse displacement of that species, which enables that ion species to pass through the filter for detection. All other ions undergo a net displacement toward the filter electrodes and will eventually be neutralized upon contact with one of the filter electrodes.
  • the compensation voltage is scanned for a given RF field, a complete spectrum of ion species in the sample can be produced.
  • the recorded image of this spectral scan is sometimes referred to as a "mobility scan", as an "ionogram", or as "DMS spectra". The time required to complete a scan is system dependent.
  • DMS operates based on the fact that an ion species will have an identifying property of high and low field mobility in the analytical RF field.
  • DMS detects differences in an ion's mobility between high and low field conditions and classifies the ions according to these differences. These differences reflect ion properties such as charge, size, and mass as well as the collision frequency and energy obtained by ions between collisions and therefore enables identification of ions by species.
  • Various chemical species in a sample can be identified according to the conventional DMS process.
  • accurate identification of several species in a sample whose detection spectra overlap is difficult. This is in part due to the fact that DMS detection peaks are relatively broad compared to a mass spectrometer, so overlap is more likely than with a mass spectrometer. In fact, where several ion species exhibit similar behavior in the DMS filter field their associated DC compensation will be very close, and so their detection spectra (detection peaks) may overlap.
  • DMS differential ion mobility spectrometer
  • FAMMS Field Asymmetric waveform Ion Mobility Spectrometer
  • the invention is directed to systems and methods for detection and identification of explosives-related compounds, (e.g., explosives or indicators of explosives like taggants) in a chemical sample by differential ion mobility spectrometry (DMS).
  • DMS differential ion mobility spectrometry
  • the invention provides an explosives detector based on aspects of differential ion mobility and with enhanced separation of ion species of interest. Embodiments achieve improved resolution between detection peaks and increased detection sensitivity. Preferred embodiments are fast operating, both with or without a pre-separator front-end.
  • taggants such as DNMB
  • a system of the present invention includes a DMS ion filter in a filter section located in a flow path after a sample delivery section.
  • the sample delivery section is for receipt of sample and delivery of ionized sample flow to the filter section.
  • the filtered separated ion species of interest pass through the ion filter section and flow to an output section of the flow path.
  • the output section has a detector, wherein detection of ion species passed by the ion filter is correlated with the analytical device conditions, and this data is compared to a lookup table or other device.
  • a species detection can be identified and presence of an associated analyte of interest in the sample (e.g., detection of an indicator of presence of an explosive compound) can be indicated.
  • the output section includes a two channel, or two mode, detector, i.e., it is capable of detection positive and negative modes (ion species) simultaneously. These modes can be related back to the ionized and filtered sample to assist in ion species and analyte identification. More specifically, a compound may be represented by either or both positive and negative ions, as such modes may be generated by ionization of the analyte molecules. In a preferred embodiment, both positive and negative modes of an ionized species can be simultaneously detected in a detection and identification section of the output. In this case, the detector includes biased detector electrodes that are capable of simultaneous detection of modes simultaneously passed by the DMS filter.
  • configuration of the flow path of a preferred embodiment of the invention enables both modes of an ionized sample to flow into the DMS filter.
  • the DMS filter can pass both positive and negative modes and which can be detected simultaneously within the time frame of a mobility scan, wherein each species mode is passed when the scanned field conditions are appropriate for that species not to be neutralized.
  • an analyte may produce ions positive and negative species and each will pass through the filter at the appropriate signature field conditions.
  • This scanned data enable a more complete detection data and more reliable identification than having only one mode as might be detected from systems only capable of single mode detection (by structural constraints, by slow cycle times, or the like.
  • Preferred embodiment of the invention are compact and fast operating with fast scan rates and in addition benefit from dual mode capability.
  • the result is fast and more reliable explosives detection in a compact and even portable system.
  • discrimination of ions from each other according to mobility differences is achieved wherein the RF field and the selected compensation enables a particular ion species to pass though the filter.
  • a plot of detection intensity versus compensation for a given FR field strength identifies an in species by its characteristic mobility differences in the compensated high-low varying DMS field. Species can be identified according to the applied conditions and peak location along the Vc axis. Peak height indicates detection intensity for those conditions and which may be correlated with detection quantity.
  • a GC -DMS apparatus of the invention pre-separation of the sample using a GC refines the sample and eases the competitive ionization that occurs with an unseparated sample. This is useful but not essential and practices of the invention detect explosive-related materials by direct sampling.
  • use of a GC also adds retention time as an additional indicator of detected species. As a result DMS data and retention time can be correlated to provide orthogonal detection data for still more reliable explosives identifications.
  • a preferred "plate-type" DMS which can perform DMS scans in a second or less and even in milliseconds, while prior art DMS devices can take many seconds to perform a single scan.
  • single mode or dual mode detection data is combined with filter field parameter data and this is combined with the separation data representing a first pre-separation (SPE, SPME, GC or the like) to enable highly reliable identification of the analyte of interest, even at trace levels.
  • SPE first pre-separation
  • a compact and reliable smart explosives detection system can be deployed in buildings or as portable devices.
  • some embodiments of the present invention may be practiced in method and apparatus using the above prefened DMS or may use coaxial cylindrical, planar, radial and other DMS electrode configurations and still will remain within the spirit and scope of the present invention.
  • FIGS. 1 A - ID show a schematic diagram of a Differential Ion mobility
  • DMS Spectrometer
  • FIG. 2 shows detector signal strength versus compensation voltage Vc for several detected ions without dopant addition in practice of an embodiment of the invention
  • FIG. 3 shows the observed increase in the compensation voltage VC for TNT with increasing concentration of several dopants in practice of an embodiment of the invention
  • FIGS. 4A and 4B show the observed increase in the compensation voltage VC for PETN with increasing concentration of several dopants in practice of an embodiment of the invention
  • FIG. 5 A shows a graph of the electric field dependence of alpha ( ⁇ ) for several explosives without addition of a dopant in practice of an embodiment of the invention
  • FIG. 5B shows a graph of the electric field dependence of alpha ( ⁇ ) for the explosives in FIG. 5 A with addition of a CH 2 C1 2 in practice of an embodiment of the invention
  • FIGS. 6 A - 6C show DMS spectra for a mixture of explosives without dopant
  • FIG. 7 shows DMS spectra for the mixture of FIG. 6B obtained by coupling a fast GC with elution time on the order of 2-3 seconds to a fast DMS in practice of an embodiment of the invention
  • FIG. 8A-8B shows reduced pressure (0.5 atm) response (A) of DMS spectra for several explosives compared to spectra at 1 atm (B);
  • FIG. 9 shows Table 2 with a listing of illustrative experimental conditions and results obtained for a combination of several explosives/taggants and dopants in practice of an embodiment of the invention
  • FIGS. 10 is a diagram of the relative electron affinities and proton affinities for exemplary explosives and dopants in practice of an embodiment of the invention
  • the invention is directed to systems and methods for detecting and identifying unknown constituents in chemical substances by aspects of differential ion mobility.
  • the systems and methods described herein can be used to detect explosives-related compounds, whether explosives material per se or taggants or the like used with explosives, using DMS technology.
  • An illustrative DMS system of the invention is shown in FIG. 1 A, which is a schematic block diagram of a DMS spectrometer 10, which operates by drawing a fluid (e.g., gas), indicated by arrow 12, via an optional pump 38 into an ionization region 18.
  • a fluid e.g., gas
  • the sample flow e.g., a gas flow carrying an analyte(s) to be detected
  • an ionization source wherein at least the analyte is ionized although the carrier gas is normally part of the ionization process as well, for example by a radioactive 63 Ni source, UV lamp, plasma source, or the like.
  • the ionized sample passes between electrode plates 20 and 22 of ion filter 24, which may be assisted by use of a transport mechanism, such as a transport gas flow.
  • An asymmetric high-low oscillating RF electric field driven by an RF voltage generator 28 is developed between the electrodes transverse to the gas flow between the ion filter plates 20 and 22.
  • the ions move in the asymmetric field with a zigzag motion along the flow path 26. Without an additional applied bias voltage, only ions whose displacement during high field cycle equals their displacement during the low field cycle pass through the ion filter. All other ions will be driven into the filter electrodes and are neutralized by contact. Once neutralized, the neutral molecules will be transported by the transport gas out of the filter.
  • the passed ion species is detected downstream, such as at detector 32. (It will be appreciated that the output of the DMS filter may be detected off board, such as in a mass spectrometer or other detector, although the preferred practice is a shown.)
  • the DMS system is tunable, i.e., is adjusted to select ions of interest, by applying a perpendicular, DC tuning field, also referred to as compensation electric field or compensation voltage Vc, superimposed on the oscillating asymmetric RF field.
  • a perpendicular, DC tuning field also referred to as compensation electric field or compensation voltage Vc
  • the DC compensation (Vc) is superimposed on the RF field at the filter electrodes 20, 22, as will compensate the travel of a selected ion species in the ion filter.
  • the compensation is selected or adjusted to allow specific ions that would otherwise be deflected towards one or the other of the electrodes to pass through filter 24 to the detector 32 without neutralization.
  • An exemplary detector 32 includes a top electrode 33 and a bottom electrode 35, and measures the charges deposited on the electrodes by the ion species.
  • the electrodes can detect positively and negatively charged ions depending on the polarity of the voltage applied to the electrodes, simultaneously.
  • multiple ion species can be detected by using top electrode 33 as one detector and bottom electrode 35 as a second detector.
  • Species detection and explosive identifications are made based on measuring the detected charges which are then associated with extant field conditions and applied compensation and this is then compared to historical data. A match of data enables identification of the detected ion species, such as TNT, DMNB, etc.
  • the system is controlled by a controller (not shown), which preferably includes an RF generator, a DC amplifier for applying the RF and compensation, as well as amplifiers for the detector electrodes, a data store, and an output or human interface.
  • a controller not shown
  • RF generator preferably includes an RF generator, a DC amplifier for applying the RF and compensation, as well as amplifiers for the detector electrodes, a data store, and an output or human interface.
  • K yp-
  • v the velocity of the ions
  • E the applied electric field
  • the electric-field-dependent mobility coefficient ⁇ (E/N) can define a unique mobility signature for the ion species which is device-independent.
  • ⁇ (E/N) relates the size, effective cross-section, shape, and mass of the ion to the electric field conditions. It is understood that the increasing electric field tends to displace, stretch, and/or break the bonds of the ion, thereby inducing dipole, quadruple, or higher order moments of the ion.
  • the functional dependence of ⁇ (E/N) on the electric field can be expressed as follows:
  • K(E/N) K(0) -[l + a 2 (E/N) 2 +a 4 (E/N) 4 + ], wherein ⁇ ; are ion-specific coefficients for even powers of the electric field E and N represents an ion density. Odd powers of E are absent since the absolute value of the velocity is independent of the electric field direction.
  • the effective electric field applied to the ions passing between the plates 22, 24 must be zero for the ions to reach the detector 32. Accordingly, the velocity impressed on the ions by the compensation electric field Vc must be equal to the time-averaged velocity impressed on the ions by the asymmetric RF field 28. This yields the following equation for the compensation electric field Vc:
  • the value of the compensation electric field Vc is hence related the ⁇ - parameter for the ion species, and the time dependence of the amplitude of the asymmetric RF waveform E ⁇ t).
  • the relationship between differential ion mobility, compensation and the ⁇ -parameter, are described in more detail in commonly assigned US patent application Serial No. 10/187,464, which is incorporated herein by reference in its entirety.
  • a scan of the compensation voltage Vc provides a measure of all ions in the analyzer, and is referred to generally as differential mobility spectra ( Figure 1 B).
  • Embodiments of the present invention can provide rapid and accurate indications of explosives detections.
  • samples are drawn into the DMS flow path without a prefilter or alternatively using a membrane or other separator.
  • the DMS device is compact and therefore dramatically reduces detection time.
  • This device can also be beneficially used as a detector for a chromatographic separator, such as a Gas Chromatograph (GC)
  • FIG. IB An illustration is provided in FIG. IB, where the GC capillary 70 delivers the separated eluent flow to the flow path at 72 and the eluent in turn is picked up in a transport gas (such as nitrogen or air) and is carried as an analyte carrying sample into the ionization region 74.
  • a transport gas such as nitrogen or air
  • the ions travel at a desired velocity (e.g., around 6 meters per second for an ion filter 15 millimeters long, separated by a 0.5mm gap).
  • the gas flow velocity defines the ion velocity through the filter.
  • the flow rates of the GC sample eluting from the column may be adequate for directly feeding into the DMS or may be assisted by use of a transport gas to augment the sample flow from the GC column. It will be appreciated by a person skilled in the art that by controlling the flow rate of the carrier gas in the GC column (or the ratio of carrier gas to sample) relative to the volume flow rate of the transport gas, various dilution schemes can be realized as desired. If the DMS must detect a high concentration of sample it is desirable to dilute the amount of this sample in a known manner so that the system operate in an optimal range of sensitivity without saturation.
  • a DMS of the invention is coupled to the GC preseparator.
  • we tightly control the dimensions of the DMS and preferably provide a short flow path from the ionization side to the detection side of the ion filter section 24. While prior art concentric cylindrical DMS devices had achieved about a 10 second scan rate, devices of the present invention can run a complete spectral scan in one second and even in the millisecond range.
  • Prior art devices achieve dwell times on the order of 200ms while devices of the invention can operate at about 1-2 milliseconds.
  • Fast operating devices of the invention can have a residence time of at or around 2.5 milliseconds and less.
  • a preferred embodiment includes a low- capacitance plate-type DMS design that enables rapid cycling and high DMS scan rates with reduced power requirements. These devices are operable with high RF fields, even in the low megahertz range and even up to five or even 10 MHZ, while the prior art concentric cylindrical DMS devices typically operate in the below megahertz range.
  • Preferred DMS devices of the invention have a gap defined between the filter electrodes 22, 24 of less than 1mm and preferably 0.5mm, and measure approximately a few millimeters width by about 15 millimeters in length. It is a feature of such design that the flow path 26 and ion filter 24 and preferably also the detector 32 are all formed on a supporting substrate, such as substrates 52 and 54 of FIG. 1A.
  • the ion filter is formed on insulating surfaces of the substrates.
  • the benefit of being able to lay down electrodes on such insulating surfaces is that it lends itself to compact packaging and volume manufacturing techniques .
  • the ion filter is defined on these insulated surfaces by the filter electrodes, facing each other over the flow path, while the insulated surfaces of the substrates, such at region X, isolate the control signal at the filter electrodes from the detector electrodes 33, 35 to assure lower noise and improved performance.
  • embodiments of the invention include a GC-DMS invention with feature a multi-functional use of the DMS substrates.
  • the substrates are platforms (or a physical support structures) for the precise definition and location of the component parts or sections of the DMS device.
  • the substrates form a housing, enclosing the flow path with the filter and perhaps the detector, as well as other components enclosed.
  • This multi-functional design reduces parts count while also precisely locating the component parts so that quality and consistency in volume manufacture can be achieved.
  • the smaller device also has unexpected performance improvements, perhaps because of the shorter drift tube and perhaps also because the substrates also perform an electronic isolation function.
  • the substrates By being insulating or an insulator (e.g., glass or ceramic), the substrates also can be a direct platform for formation of components, such as electrodes, with improved performance characteristics and reduced capacitance.
  • the GC-DMS sensor with insulated substrate/flow path achieves excellent performance in a simplified structure. Sensitivity of parts per billion and possibly parts per trillion can be achieved in practice of the disclosed invention.
  • the ion filter electrodes and detector electrodes can be positioned closer together which unexpectedly enhances ion collection efficiency and favorably reduces the device's mass that needs to be regulated, heated and controlled. This also shortens the flow path and reduces power requirements. Furthermore, use of small electrodes reduces capacitance which in turn reduces power consumption. Quite favorably, depositing the spaced electrodes lends itself to a mass production process, since the insulating surfaces of the substrates are a perfect platform for the forming of such electrodes. This may be performed in a single chip-like electronics package.
  • the substrates as a support/housing does not preclude yet other "housing" parts or other structures to be built around and containing a GC-DMS device of the invention. Furthermore, it is possible to put a humidity barrier over the device. As well, additional components, like batteries, can be mounted to the outside of the substrate/housing, e.g., in a battery enclosure. Nevertheless, embodiments of the presently claimed invention stand over the prior art by virtue of performance and unique structure generally, and the substrate insulation function, support function, multi-functional housing functions, specifically, as well as other novel features.
  • the substrates cooperate to form a device housing in that the subsfrates assist enclosing the flow path while also enabling mounting of the component parts.
  • This multi-use, low parts-count housing configuration enables smaller real estate and leads to a smaller and more efficient operating DMS device, even smaller than 1" x l" x l".
  • the Spectrometer section 10 is formed with spaced insulated subsfrates 52, 54, (e.g., Pyrex® glass, Teflon®, pc-board) having the filter electrodes 20, 22 formed thereon (of gold, platinum, silver or the like).
  • the substrates 52, 54 further define between themselves the input part (such as for receipt of sample S and transport gas 16) and output part (such as detector 32), along flow path 26.
  • detector 32 has detector elecfrodes 33, 35 mounted on the substrate insulated surfaces 53, 55, facing each other across the flow path 26.
  • either insulating or conducting spacers 56 serve to provide a controlled gap between electrodes 20 and 22 and define the enclosure of the flow path.
  • the spacers may be formed by etching or dicing silicon wafers, but which may also be made of patterned Teflon, ceramic, or other insulators. These spacers may be part of the subsfrates forming a complete sidewall 56' or may be separate elements, such as layers 56, 56 and even may form elecfrodes 56e, 56e for heating the flow path or for confining the ion flow with an electric field. This confinement can result in more ions striking the detectors, and which in turn improves detection.
  • a heating element 57 is associated with at least one of the substrates 54, as shown in FIG. 1A.
  • the electrodes 20, 22 of filter 24 are preferably formed on the inner walls substrates 52, 54, but also with an area of exposed substrate remaining. Therefore the active area of the electrodes is kept small and keeps the capacitance low. As well, with reduced volume of such a compact "micro- machined" device, an efficient and fast operating DMS is provided. It is a preferred characteristic of the invention that the flow path 26 along its sides at least in the ion filter 24 is enclosed by the substrates alone or in cooperation with the filter electrodes and the spacers. The spacers effectively define the electrode separation, i.e., the analytical gap separating the electrodes in the ion filter 24. This compact design enables fast and reliable DMS operation and can be favorably employed in practice of embodiments of the invention.
  • some ions will be driven into the electrodes 20, 22 and will be neutralized. These ions can be purged by heating. This may be accomplished in one embodiment by heating the flow path 26, such as by applying a current to filter electrodes 20, 22, or to spacer electrodes 56, 56. As heater electrodes, they also may be used to heat the ion filter region to make it insensitive to external temperature variations.
  • Pump 39 generates flow, such as exhaust 39, in the compact structure housing/substrate structure, and may also be used for recirculation for supply of conditioned fransport gas (such as dry air) to the input part or even recirculation of the duralized detected ion species for redetection.
  • conditioned fransport gas such as dry air
  • the devices of the invention have various electrode arrangements, possibly including pairs, arrays and segments. Filtering may include the single pair of filter electrodes 20, 22. But device performance may be enhanced by having a filter array 62 having a plurality of ion filters 24a-n, each of which may have its/their own operating environment and including own assigned dopant introduction, which even better detection control and performance. It will be appreciated that it is possible to have multiple filters 24 in a serial array in a single flow path or with multiple parallel filters in multiple parallel flow paths, each with at least one assigned filter or an array.
  • the filter array 62 of FIG. IE has a plurality of paired filter elecfrodes 20a-n and 22a-n and may simultaneously pass different ion species by control of the applied signals for each electrode pair. In addition, it is possible to sweep the confrol component for each pair over a voltage range for filtering a spectrum of ions.
  • each filter can be used to scan over a smaller voltage range. The combination of all of these scans results in sweeping the desired full spectrum in a reduced time period. If there are three filters, for example, the spectrum can be divided into three portions and each is assigned to one of the filters, and all three can be measured simultaneously.
  • filter array 62 may include the pairs of filter electrodes 20a- e and 22a-e and may simultaneously enable detection of different ion species by applying a different compensation bias voltage to each filter of the array, without sweeping. In this case, only an ion species that can be compensated by this fixed compensation voltage will pass through each filter, and the intensity will be measured. This dedication to a particular analyte of interest can be greatly enhanced by selection of a species-specific detection-enhancing dopant associated with improved detection of that species.
  • array 62 may include any number of filters depending on the size and use of the spectrometer.
  • doping is broadly defined as the process of adding an analyte for the purpose of affecting ion species behavior.
  • Doping may include the step of addition of an analyte in the ionization process whose ionization releases free electrons which enables ionization of negative species.
  • Doping may include the step of use of an additive to improve ionization efficiency.
  • Doping may include the step of addition of an analyte that affects species behavior and causes peak shift. Referring back to FIG.
  • the illustrative DMS spectrometer of the invention is interfaced with a gas chromatograph (GC) in which a gaseous sample or and liquid sample, such as a solution containing an explosive to be analyzed, is injected.
  • a gaseous sample or and liquid sample such as a solution containing an explosive to be analyzed
  • the sample is transported through the GC and emerges after an elution time RT at the output of the GC where it is injected via a heated transfer line 14 into a transport gas flow 12.
  • the transport gas flow 12 may also include a dopant flow 16, as depicted in FIG. 2.
  • the dopant can be supplied by flowing a gas, such as H 2 , N 2 , Ar, He and the like, through a bubbler (FIG.
  • the dopant in liquid or solid form, or the dopant can be stored in gaseous form in a gas tank and enter the transport gas stream at a predetermined rate through a controlled leak. It will be understood that the flow rates of the transport gas and the dopant can be controlled by employing flow meters known in the art.
  • the DMS can operate under atmospheric pressure, thereby reducing the need for a pump, but may also be operated at reduced pressure for some species of interest, where reduced pressure can improve the sensitivity and resolution of the instrument.
  • FIG. 8 shows detection of TNT, DNT, NG and EGDN in practice of the invention at 0.5 atm at 120°C. Compared to operation at 1 atm, the peaks shifted 5 volts on the Vc axis, which is a tool that enables shifting of peaks in a cluttered sample or away from interfering peaks, or even offset from the background spectra (RIP).
  • an illustrative DMS analyzer was operated using specialized electronics containing separation waveform generator, a compensation voltage amplifier, and two-polar electrometer (for the detector).
  • the separation waveform generator was based on a soft-switched, semi-resonant circuit that incorporated a fly-back transformer and allowed variable peak-to-peak amplitudes of the asymmetric waveform from 200 V to 1600 V without altering the waveform shape.
  • the operating frequency of the generator was 1.3 MHz and the amplitude was between 950 and 1200V.
  • a compensation voltage amplifier was controlled by data collection software and was scanned between 30 to -10 V in ⁇ l sec periods.
  • Two Faraday plate detectors floated 5 V ⁇ provided simultaneously detection of positive and negative ions (modes) during one scan of the compensation voltage. Signal was processed to digitize and store spectra for every scan. Conventional software was used to confrol DMS hardware, to collect DMS spectra, to save data and to display the results.
  • NT 4-nitrotoluene
  • DNT 2,6-dinitrotoluene
  • TNT 2,4,6-trinitrotoluene
  • NB 4-nifrobenzene
  • DNT 2,6-dinitrotoluene
  • TNT 2,4,6-trinitrotoluene
  • NB 4-nifrobenzene
  • DNT 2,6-dinitrotoluene
  • TNT 2,4,6-trinitrotoluene
  • NB 4-nifrobenzene
  • DNB 1,3-dinifrobenzene
  • TNB 1,3,5-trinifrobenzene
  • TRB 1,3,5-triazine, hexahydro- 1,3,5-trinifro
  • RDX 1,2,3-propanetriol
  • NG pentaerythritol, tefranitrate
  • PETN pentaerythritol, tefranitrate
  • Co initial concentration
  • W volume of exponential dilution flask
  • Q carrier gas flow rate regulated by a flow controller
  • t time.
  • the gas flow was then delivered to a DMS analyzer through heated lines to minimize adsorption of sample on the tubing. Temperatures needed for explosives to obtain gas concentrations without adsorption or thermal decomposition ranged from 100 to 240°C and were compound specific.
  • dopants can be introduced from a solid, liquid or gaseous source.
  • a vapor generator was used to provide constant concentration of modifying chemical into the transport gas for GC DMS studies.
  • the vapor generator included a saturated vapor source, under temperature control, and a source of purified gas, e.g. air.
  • Flow controllers were used for controllably mixing the gas containing the dopant with the transport gas.
  • w can detect explosive materials per se, without dopant, as shown in FIG. 2. Differential mobility spectra for nitrated aromatic compounds and explosives in purified air are shown in FIG.
  • the DMS operated at atmospheric pressure without added dopant.
  • the detected ions were either positive (o-MNT, p-MNT, DMNB, TATP, HMTD), negative (HMX, Tetryl, PETN, RDX, TNT, DNT, NG, EGDN), or both positive and negative (RDX, AN). Little fragmentation had occurred apart from a barely discernible peak for NG (at -20 V) and peaks of low intensity for PETN and RDX (also at -20 V).
  • FIG. 3 the influence of various dopants, such as H 2 O, methanol, isopropanol, acetone and methylene chloride, on the compensation voltage for DNT is shown.
  • various dopants such as H 2 O, methanol, isopropanol, acetone and methylene chloride
  • FIGS. 4 A and 4B the addition of acetone and methylene chloride in concentrations of approximately 3,000 to 10,000 ppm causes a dramatic increase in the compensation voltage Vc for DNT.
  • other explosives in this case PETN, respond differently to the same dopants.
  • PETN only methylene chloride and methylene bromide (FIG. 4B) cause a significant increase in Vc- A change in the compensation voltage therefore depends on a combination of the explosive substance and the dopant species and cannot be estimated in advance.
  • the compensation voltage and the ⁇ -values that characterize the field-dependent mobility are related, so that the ⁇ -values can be determined from a measurement of Vc.
  • FIGS. 5 A and 5B shows graphs of ⁇ versus E/N for explosives at 0.1 ppm moisture in air at 150°C.
  • FIG. 5A the ⁇ - function is plotted for experimental conditions where no dopant was added. The difference of ⁇ between low and high electric field conditions is only -0.005 to 0.02. This is less than half the values obtained for ketones (from acetone to octanone) which have ⁇ -values between 0.05 and 0.1.
  • These graphs are the first reported graphs for negative ions. The results suggest that best ion separation will occur with E/N values of ⁇ 120, corresponding to an electric field of 1200 V/cm at 660 Torr ambient pressure.
  • FIG. 5B the addition of methylene chloride (CH 2 C1 2 ), chosen on the basis of the observed shift of the compensation voltage Vc with dopant concentration plotted in FIGS. 3, 4A and 4B, causes a dramatic change in the ⁇ - functions.
  • the differential mobility specfra for explosives with approximately 1000 ppm methylene chloride in air in the gas flow shown in FIG. 5B may be directly compared to the plots shown in FIG. 5A.
  • the presence of the dopant-modified vapor has caused either a change in the ion identities or in the ion behavior in the analyzer. Changes in the vapor concenfration of the explosives cause no change in the compensation voltage of the ions or changes in DMS spectra.
  • mass spectra showed nearly complete replacement of 0 2 (H 2 0) n with Cl 2 (H 2 0) n for the reactant ions.
  • Reaction chemistry may be partially responsible for some of the changes in DMS specfra.
  • mass spectra demonstrated that chloride ion caused the formation of M» Cl ⁇ (H 2 0) n fo ⁇ NG replacing M » N0 2 as the primary ion.
  • new peaks may arise from M • Cl ⁇ (H 2 0) n and hydride absfraction in the drift tube, rather than in the DMS/MS (mass spectrometer) interface.
  • the mass spectrum for PETN was largely comprised of fragment ions and was consistent with peaks near 12 V in the DMS spectra. Fragments in the mass spectrum supported fragmentation in the differential mobility spectrum for TNT. Those ions most dramatically affected by addition of methylene chloride in the transport gas showed little if any discemable differences in mass specfra. It may therefore be inferred that the ion was present as two different species, depending on the applied electric field: M ⁇ +C 2 Cl 2 ⁇ >M ⁇ *C 2 Cl 2
  • an illustrative GC-DMS spectrometer 10 of the invention includes a gas chromatograph (GC) as a pre-separation stage.
  • GC gas chromatograph
  • the pre-separation step adds retention behavior to compensation voltage for enhanced specificity, and the introduction of constituents as single constituents or an elution peak with a few compounds increases the reliability of APCI reactions.
  • Results from GC/DMS determinations of explosives in a mixture are shown in FIGS. 6A-6C where only air is used as the transport gas. The specfra were taken with the DMS operating at atmospheric pressure.
  • FIG. 6A shows a contour plot of the DMS response for a mix of RDX, PETN, TNT and NG without an added dopant.
  • the addition of 1000 ppm methylene chloride (CH 2 C1 2 ) dopant in the transport gas significantly enhances the signatures of RDX, PETN, TNT and NG DMS spectra.
  • FIG. 6C shows an even more profound effect is observed when chloroform (CHC1 3 ) is added as dopant.
  • FIG. 7 shows DMS spectra for the mixture of FIG.
  • the response time and overall analytical performance of a DMS for explosives can be assisted by selection of suitable dopants with a GC pre-separator.
  • a GC pre-separator is not required for detection of explosive- related ion species in alternative practices of the invention.
  • DMS spectra for specific explosive and dopant combinations depend on several variables, such as Vrf and Vc as well as transport/flow rate and pressure in the flow path.
  • FIGS. 6A-C shows DMS spectra at 0.5 atm pressure for detection of ionized explosives analytes for TNT, DNT, NG and EGDN which can be compared to the 1 atm spectra of FIGS. 6A-C.
  • lowering the pressure shifts the peak position, which is indicated in changes in the required compensation voltage Vc, compared to the 1 atm data.
  • the specfra of FIGS. 6A-C and FIG. 7 are only shown for negative mode detections, it will be understood by those skilled in the art that positive mode detections may have valuable data for those substances (i.e., a particular analyte may be indicated by formation of both positive and negative species, according to the signature characteristics of the ionized analyte).
  • FIGs. 8A - 8B show reduced pressure response for a DMS system of the invention (0.5 atm) for several explosives compared to specfra taken at 1 atm.
  • the left-hand frame (A) shows background spectra (RIP) from ionization of the carrier gas (air) at 1 atm and interference with detection peaks for TNT, DNT, NG, and EGDN.
  • RIP background spectra
  • FIG. 9 is a Table listing illustrative DMS detections for several combinations of explosives/taggants without and with addition of dopants.
  • dopants were used in the experiments: methyl bromide (CH 2 Br 2 ), methyl chloride (CH 2 C1 2 ), methanol (CH 3 OH), and isopropanol.
  • the following explosives were investigated were investigated: HMX, Tetryl, PETN, RDX, NG, TNT, EGDN, DNT, o-MNT, p-MNT, DMNB, TATP, HMTD and AN.
  • Table 1 For an explanation of the used abbreviations, see Table 1.
  • Rf denotes the peak-to-peak amplitude in the DMS filter.
  • HMX, Tetryl, PETN, RDX, and NG were detected as having identifiable detection peaks in the negative mode with four dopants.
  • TNT and EGDN were detected in the negative mode with CH 2 C1 2 , CH 3 OH, and isopropanol, but not with CH 2 Br 2 .
  • DNT was detected in the negative mode with CH 3 OH and isopropanol, but not with CH 2 Br 2 and CH 2 C1 2 .
  • o-MNT, p-MNT, DMNB, TATP, and HMTD were detected in the positive mode having minor Vc shifts.
  • both modes may be passed simultaneously by filter 24 and both may be detected by oppositely biased detector elecfrodes 33, 35.
  • a bias on one electrode both attracts the oppositely charged ions and also deflects the same charged ions to the opposite detector electrode. Therefore a fast-operating DMS with high detection efficiency can be implemented in practices of the present invention.
  • Prior art DMS/FAIMS devices have not benefited from such configuration.
  • FIG. 10 shows electron affinities of listed explosives in relation to the electron affinities of the dopants.
  • CH 2 Br 2 the electron affinity of methylene bromide
  • electrons are transferred from methylene bromide to HMX, Tetryl, PETN, RDX, or NG, forming complexes that are detected through a signature shift of Vc-
  • TNT and EGDN are not detected with methylene bromide.
  • DNT can be detected with methanol and isopropanol, but not with CH 2 Br 2 or CH C1 2 .
  • a similar trend can be inferred for the positive ion species mode.
  • each channel carries at least one of the dopants and receives an unknown mixture of analytes, such as the aforedescribed explosives.
  • the values of the compensation voltages Vc measured in each channel, in conjunction with the known electron/proton affinities, can then be used to reliably determine the chemical composition of the analyte.
  • dopants for the detection of explosives is merely exemplary, and that other chemicals can also be detected.
  • a new method of enhancing resolution or selectivity in differential mobility spectrometry has been developed through modification of the transport gas with a small amount of dopants and has been applied for the determination of explosives with the preferred DMS having a compact, plate-type, "micro-fabricated" flow path (drift tube).
  • DMS digital signal processor
  • Addition of 1,000 ppm of methylene chloride into the purified air transport gas increased the field-dependence of the mobility for explosive ions 3-6 times, as expressed in the observed increase in the compensation voltage.
  • DMS practices of the invention enable detection of explosives substances on a part per billion level with a response time about approximately one second.
  • DMNB represents a taggant added to explosive materials for security purposes.
  • DMNB has the chemical formula 2,3- dimefhyl-2,3-dinitro-n-butane (C 6 H 12 N 2 O 4 ).
  • Taggants have experienced renewed interest due to government supported anti-terrorist activity, especially after September 11, 2001. Use of taggants serves two different functions and thus uses two different kinds of taggants.
  • a first type of taggant aids in the detection of explosives prior to detonation by using appropriate detection equipment.
  • a second type of taggant is designed to survive an explosive blast and helps in the identification of the particular explosive material. It can be recovered at the bomb scene and provide traceable sourcing information related to the explosives' purchase history.
  • the United States has officially designated DMNB as a detection taggant for plastic explosives.
  • DMS spectrometers of the invention can be fine-tuned for specific chemical substances, as described above. As will be described below, DMS spectrometers can be used to detect taggants and to distinguish the taggant signal from that of the background.
  • o-MNT ortho-mononifrotoluene
  • p-MNT para- mononifrotoluene
  • DMNB 2,3-dimethyl-2,3-dinifro-n- butane
  • Figure 11 shows detection of DMNB taggant introduced at a trace amount of 200 micro liters in an air transport at 0.4L/min is shown, with the DMS separation field operated at an RF having Rmax of 1300v.
  • DMNB fragment spectra are detected at about -25 Vc and a DMNB-related molecular specfra is at about -4 Vc.
  • positive mode detections (left frame) of DMNB taggant signature clearly stand out over the background specfra.
  • Negative mode detections also show a small DMNB-related peak at around -31 Vc.
  • DMNB taggant at 200 micro liters in a nitrogen gas transport at 0.4L/min, with Rmax of 1300v.
  • DMNB fragment spectra are detected at about -21 Vc with a related molecular peak at about -4 Vc, in the positive mode (left frame).
  • negative detection spectra are seen for a DMNB-related peak at about -31 Vc in the right frame. All are well separated from the background spectra.
  • FIG. 13 detection of DMNB taggant introduced at a trace amount of 200 micro liters in an air fransport at 0.4L/min is shown, with Rmax of 1500v. Fragment spectra are detected at about -35 Vc and a molecular specfra is seen at about -4 Vc. These positive mode detections (left frame) of taggant signatures clearly stand out over the background spectra. As well a smaller DMNB signature peak is seen in the negative mode at about -35 Vc.
  • FIG. 14 we show detection of taggant at 200 micro liters in a nitrogen gas transport at 0.4L/min, with Rmax of 1500v. Fragment spectra are detected at about - 33 Vc with a molecular peak at about -4 Vc in the left frame. In addition, DNMB negative detection spectra are seen at about -38 Vc in the right frame. All are well separated from background specfra.
  • the data source is accessed as a lookup table and has a range of detections of explosives-related analytes.
  • a single comparison may be adequate where a system is dedicated to detection of a particular species.
  • An optimized set of RF and compensation values may be selected, which may include values representing selected pressure. These optimized parameters are selected to meet the criterion of increased reliability in identification by detection data set. Presence or absence of a species can be indicated by conventional announcement means.
  • DMS performance to enable improved explosives detection based on differences in ion mobility-related behavior. Species are separated, detected and identified based on this optimization. We can further optimize the process by detecting ion polarity, and we can optimize ionization and/or separation by using dopants. Thus in practice of the present invention, we apply various strategies for improved isolation, detection and identification of explosives-related chemicals in a sample based on aspects of differential ion mobility behavior.

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Abstract

L'invention concerne un système destiné au contrôle du comportement d'espèces d'ions dans un filtre à variation dans le temps d'un spectromètre basé sur la mobilité d'ions pour améliorer l'identification d'espèces à des fins de détections d'explosifs.
PCT/US2004/010862 2003-04-08 2004-04-08 Detection d'explosifs utilisant une spectrometrie a mobilite differentielle d'ions WO2004092704A2 (fr)

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Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007042763A2 (fr) * 2005-10-07 2007-04-19 Smiths Detection-Watford Limited Generateurs de vapeur
CN102568994A (zh) * 2010-12-31 2012-07-11 同方威视技术股份有限公司 用于离子迁移谱仪的进样装置及其使用方法和离子迁移谱仪
GB2537995A (en) * 2015-04-14 2016-11-02 Micromass Ltd Ion mobility separation buffer gas composition
WO2018142126A1 (fr) * 2017-01-31 2018-08-09 Smiths Detection-Watford Limited Procédé et appareil
CN108899264A (zh) * 2018-06-07 2018-11-27 中国科学院合肥物质科学研究院 一种高灵敏高场不对称波形离子迁移谱检测装置
CN113138225A (zh) * 2021-06-04 2021-07-20 山东大学 一种不同湿度大气中氨气的化学电离质谱分析系统和方法

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* Cited by examiner, † Cited by third party
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No further relevant documents disclosed *

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Publication number Priority date Publication date Assignee Title
EP3300783A1 (fr) * 2005-10-07 2018-04-04 Smiths Detection-Watford Limited Générateurs de vapeur
WO2007042763A3 (fr) * 2005-10-07 2008-11-20 Smiths Detection Watford Ltd Generateurs de vapeur
US8137437B2 (en) 2005-10-07 2012-03-20 Smiths Group Plc Vapour generators
WO2007042763A2 (fr) * 2005-10-07 2007-04-19 Smiths Detection-Watford Limited Generateurs de vapeur
US8778060B2 (en) 2005-10-07 2014-07-15 Smiths Detection-Watford Limited Vapour generators
CN102568994A (zh) * 2010-12-31 2012-07-11 同方威视技术股份有限公司 用于离子迁移谱仪的进样装置及其使用方法和离子迁移谱仪
GB2537995A (en) * 2015-04-14 2016-11-02 Micromass Ltd Ion mobility separation buffer gas composition
GB2537995B (en) * 2015-04-14 2019-12-25 Micromass Ltd Ion mobility separation buffer gas composition
WO2018142126A1 (fr) * 2017-01-31 2018-08-09 Smiths Detection-Watford Limited Procédé et appareil
CN110431411A (zh) * 2017-01-31 2019-11-08 史密斯探测-沃特福特有限公司 方法和装置
GB2560632B (en) * 2017-01-31 2020-01-29 Smiths Detection Watford Ltd Method and apparatus for Ion mobility spectrometry with controlled water dosing
GB2575929A (en) * 2017-01-31 2020-01-29 Smiths Detection Watford Ltd Method and apparatus
GB2575929B (en) * 2017-01-31 2020-04-22 Smiths Detection Watford Ltd Indicating maintenance status for an IMS device.
CN108899264A (zh) * 2018-06-07 2018-11-27 中国科学院合肥物质科学研究院 一种高灵敏高场不对称波形离子迁移谱检测装置
CN113138225A (zh) * 2021-06-04 2021-07-20 山东大学 一种不同湿度大气中氨气的化学电离质谱分析系统和方法

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