Ion Mobility Spectrometry and Its Applications inDetection of Chemical Warfare AgentsMarko A. Makinen

University of Eastern Finland

Osmo A. Anttalainen

Environics Oy (Finland)

Mika E. T. Sillanpaa

Lappeenranta University of Technology and University of Eastern Finland

When fast detection of chemical warfare agents in the fieldis required, the ion mobility spectrometer may be the onlysuitable option. This article provides an essential surveyof the different ion mobility spectrometry detection tech-nologies. (To listen to a podcast about this feature, pleasego to the Analytical Chemistry multimedia page at pubs.acs.org/page/ancham/audio/index.html.)

The threat of weapons of mass destruction (WMDs), such aschemical warfare agents (CWAs) and toxic industrial chemicals, isof great concern worldwide. This menace makes it necessary todetect the presence of such weapons in both military and civilenvirons. Toxic chemicals are used in large quantities by industry,and the information needed to synthesize them has become moreaccessible through the Internet. In addition to providing protectionfrom chemical attacks, fast detection is needed to detect possiblechemical leaks which may occur during accidents, disposal, ordumping. Many of these chemicals are hazardous to human health;others may be inflammable or pose environmental risks.

The purpose of this Feature is to highlight how ion mobilityspectrometry (IMS) technologies can be applied to the detectionand identification of these chemicals. The properties of the mostcommon CWAs are described, and the principles, limitations, andadvantages of analytical IMS detection together with its futureprospects are discussed.

INTRODUCTION TO CHEMICAL WARFAREAGENTSToxic chemicals have great potential to inflict significant casualties,thus chemical weapons are classified as WMDs. Furthermore,

CWAs are easy to disguise and are practically imperceptible, thusmaking them easy to use against the public. CWAs are mostlydispersed as vapors or aerosols; the more volatile the agent is,

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the faster it evaporates and disperses. In addition, CWAs or theirdegradation products may linger as soil contaminants. Structuresof common CWAs are shown in Figure 1. Earlier articles haveevaluated the different technologies for detection of CWAs.1,2

Classification of CWAs. CWAs are divided into five differentcategories.3,4

i) Vesicating and blistering agents such as sulfur and nitrogenmustards cause extensive and irreversible tissue damage. Lewisiteis the most infamous of the organoarsenic warfare agents. ii)Choking agents or pulmonary intoxicants are, for example, phos-gene, which does not detoxify naturally, has a cumulative effect,and may persist in sheltered areas or buildings for a long timeand chlorine, which at moderate concentrations is a weakpulmonary irritant but in high concentrations is extremely lethal.Both are also indispensable industrial chemicals. iii) Nerve agentsare organophosphonates, which are further divided into threesubcategories: G agents (G denotes German origin), such asTabun (GA), Sarin (GB), and Soman (GD); V agents (mainly VX;some variants exist); and Novichok agents. Tabun was initiallyused as a pesticide but has been utilized for military purposes.Sarin is an extremely volatile colorless liquid that has a mild aromaof rotting fruit if impure. Soman is more poisonous than the twoaforementioned and has a camphor-like odor if impure. VX is anodorless liquid with an appearance similar to motor oil. Novichoksare considered to be the most hazardous agents ever made.5 iv)Blood-born agents are cyanogens such as HCN and CNCl. Theyare distributed by the vascular system. v) Incapacitating agentsare non-lethal CWAs. CS (tear gas) is widely used for variouspurposes. In addition, some nations are producing, stockpiling,and transporting large quantities of toxic industrial chemicals.

ION MOBILITY SPECTROMETRYPrinciples. IMS involves both ionization of the sample and

analysis of the ions formed at ambient temperature and at ambientor reduced pressure. This analytical method is used in variousdemanding applications including field or on-site detection of vaporphase species such as chemical weapons, explosives, and drugs.The first analytical device was introduced in the late 1960s,6 andCWA detectors were introduced in the 1970s and early 1980s.7

At atmospheric pressure, the ion-molecule reactions of CWAsresult in efficient formation of stable and identifiable product ions,which spurred the widespread use of IMS for CWA detection.8

IMS is used more extensively than any other method in thedetection of trace CWAs and explosives.9

Recently, appreciation of the IMS technique and its variousapplications has increased.10 IMS instruments are widely used bymilitary, security, customs, and border authorities. The majorityof the commercial instruments are used for explosives detection,11

and probably the most noticeable application is the walk-throughportals in airports used to monitor for traces of explosives.12

In IMS, gas phase ions are created by ionizing neutralmolecules using photon, corona, flame, ESI, or radioactiveionization. Most of the instruments use radioactive ionizationsources like 63Ni or 241Am because they are simple, convenient,and stable. The ions produced are separated by their differentvelocities through a drift gas in an electric field. IMS separationis based on ion mobility, with the relationship between ionvelocity and electric field depending on the ion’s weight,charge, and shape.11 The temperature, pressure, and molecularproperties of the drift gas also play important roles.13 Toremove background interference and improve sensitivity andselectivity, additional reagent gases (dopants) can be used tocreate alternate reactant ions such as Br-, Cl-, NO3

-, NO2-,

or NH4+.14 Thus, ion mobility spectrometers are similar to TOF

mass spectrometers, although operation at ambient pressurehas its own pros and cons. In case of CWAs, the instrumentsmainly operate in positive mode; i.e., the ions formed from thesamples are positively charged. However, some exceptionsexist because agents with halogen atoms and low proton affinityare unable to form stable positively charged ions.

Advantages and Limitations. There are many CWA detectiontechniques. For example, common laboratory methods and instru-ments such as GC, LC, CE, and MS, individually or in combination,may be used. On-site screening techniques include surfaceacoustic wave (SAW), electrochemical, and spectrophotometricsensors. All these techniques have their pros and cons; forexample, SAW sensors can be small and portable but are sensitiveto moisture and may suffer from de-wetting effects that reduceresponsiveness.15 Spectrophotometric techniques are based oncolor change reactions (detection papers or detection tubes) oremission lines (flame photometric detection [FPD]). Color changeexperiments are easy to perform but need a relatively high amountof sample, can be time consuming, and give ambiguous results.FPD is fast and sensitive but produces false positives. Typicaldrawbacks to all these techniques are false positives and adsorp-tion of the agents onto instrument surfaces.2 However, IMS alsosuffers from these disadvantages.

IMS as an analytical technique has several specific weaknesses.The primary drawbacks are its low resolving power, limitedselectivity,16 and the experimental nature of the technique. Matrixeffects such as humidity, temperature, and the composition of thesample may influence the detector’s response. Ideally, IMS shouldbe used in environments with controlled temperature, low humid-ity, and controlled amounts of dopants, thus requiring delicateengineering and parameter optimization for in-field use. Theseparation of ions is highly dependent on ion mobilities in a driftgas under the influence of an electric field, which may be affectedby altering the polarizability and mass of the drift gas, thuschanging the chemistry of ion-neutral molecule interactions.Selectivity could be improved by adjusting the electric fieldstrength and drift tube pressure or temperature; other ions mayalso be examined. Nonetheless, high collision rates at atmosphericpressures could be advantageous in IMS. Based on the thermo-dynamic equilibrium between the ions and the neutral molecules,IMS is able to selectively ionize whole classes of compounds withFigure 1. Structures of some typical CWAs.

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collectively unique thermodynamic properties such as high protonaffinity.

Another drawback of IMS chemical interference in highlycontaminated environments. Such interference may be reducedby using highly selective forms of ionization with additionalreagent molecules.16 However, if the measurements are made athigh pressures in which gas-phase collisions may increase thefrequency of the charge exchange reaction, the desired selectivitycannot be achieved.17 False positives also may pose a problem.Some well-known examples of interferant cross-references inexplosive trace detection include certain medications such asvasodilators containing nitroglycerin, certain ingredients in com-monly-used hand lotions, cardamom, and certain types of fire-fighting foams. These problems may be efficiently solved withinstrumental combinations like IM/MS, which could significantlydecrease the potential for false positive responses when screeningfor CWAs.18 IM/MS has already been used to analyze CWAs inspiked food products.19

The bureaucracy involved in using radioactive sources, includ-ing complying with numerous ordinances and licensing require-ments, is also a limitation. Alternative, non-radioactive atmosphericpressure ionization methods include photoionization, laser ioniza-tion, corona discharge, and surface ionization. However, non-radioactive ionization sources suffer from limited lifetimes, aging,stability, and the need for power.

Even though IMS has the above-mentioned drawbacks, numer-ous advantages tip the balance in its favor. The main advantagesof IMS are instrumental simplicity, small size, light weight,portability, reliability, ease of operation, real time monitoringcapability, fast response, short analysis time, low power consump-tion, low operating cost, and high sensitivity, specifically forpersistent CWAs.20

The analytical performance of IMS is superior to that of otherCWA detection methods. Analysis and response times of IMS arevery short, thus providing the basis for a real-time monitoringcapability: the actual ion separation time in one scan is on themillisecond timescale, and total measurement time is only a fewseconds. Common agents are easy to ionize and to analyze, leadingto relatively high reliability and sensitivity. Combining IMS withother analytical instruments such as GC and MS further increasesthe analytical power. These combinations provide a seconddimension of separation, which increases selectivity and thereforereduces the number of false positives. An example is an analysisof TNT in which hand lotion can produce a false positive. Bothsubstances produce equal signals in IMS and in MS but are

distinct in a 2D spectrum.21 This IM/MS combination can alsobe used to analyze degradation products of CWAs from a complexaqueous mixture.22

Other advantages originate from user-friendliness and practicaldetails. Instrumental simplicity and ease of use creates a largenetwork of potential users by simplifying training. The small sizeand weight allows true portability. Easy maintenance and lowpower consumption together with robustness enable IMS usagein difficult environs such as those required for military applications.

TECHNIQUES IN CHEMICAL WARFARE AGENTDETECTION

Conventional IMS. A conventional ion mobility spectrometerconsists of the reaction region, including the ion source and iongate, and the drift region and detector. The sample compoundsare ionized by proton transfer or electron capture reactions. Theelectronic gating grid (ion gate) introduces the ions into the driftregion, where the ions travel along the electric field gradient. Theions are separated according to their velocities in the neutral,counter-flowing drift gas. Ions create a drift time related signalthrough collision and neutralization at the detector (a Faradayplate). The operating principle for a conventional IMS device ispresented in Figure 2.

Detection in conventional IMS is based on signal peak positionand intensity. The selectivity is defined by resolving power, whichin turn is defined by drift time per peak half width. In general,the length of the drift tube limits the selectivity, but advancedsignal processing methods like FT may resolve this problem.Conventional IMS is difficult to miniaturize, so only a fewmanufacturers are fabricating handheld devices. Nevertheless, themajority of the instruments used for in-field detection are basedon this conventional separation and detection technique. Thecurrent commercial manufacturers of conventional handheld IMSinstruments for in-field detection include Smiths Detection, BrukerDaltonics, IUT GmbH, and GE Security.

Conventional IMS instruments have been widely used in CWAinvestigations. The early studies included pesticides,23 organo-phosphorus compounds,24 sarin,25 various phosphorus estersincluding G nerve agents,26 and methyl isocyanate.27 Morerecently, research in Hill’s group has been especially active. Theyhave analyzed the reduced mobility values of various CWAsimulants and degradation products.28,29 The combination of ESIand IMS has been used to characterize CWA degradationproducts, with detection limits <100 ppb.30 IMS combined withTOFMS has been used to study CWA simulants in different

Figure 2. The operating principle for a conventional IMS instrument.

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aerosol matrices; the main advantage of this combined technologyis that it produces both 2D and 3D acquisition spectra, thusfacilitating compound identification.31,32 With the same combina-tion, the identification and quantification of CWA degradationproducts in aquatic environments also becomes possible.22 Alter-native, non-radioactive ionization techniques like chemical ioniza-tion, ESI and secondary electrospray ionization (SESI) have alsobeen used to ionize CWA simulants, resulting in higher detectionsensitivity.33

Other studies have investigated detection limits and reducedmobility values of substances present in hazardous military wastesites,34 the problems of VX detection,35 and explosively dis-seminated CWAs.36,37 The response to phosgene has beendetermined by using membrane inlet IM/MS.38 IM/MS has alsobeen used to analyze lewisite and lewisite-mustard mixtures.39

The detection performance of corona discharge IMS has beeninvestigated using CWAs and related compounds.40

A solid phase microextraction (SPME) sampling systemcoupled with IMS has been introduced as a fast and reliableanalysis method for CWAs. Using this method, the precursor andbyproducts of GB and degradation products of VX present in soilshave been analyzed with good reproducibility and detection atconcentrations as low as 10 µg g-1.41 SPME with pyrolysis GC/IMS has been used to analyze tributylphosphate (a VX simu-lant).42 Reduced mobility values and evaluated detection limitsfor various CWAs, including G-agents, mustard gas, andV-agents, have been studied with high-temperature SPME/IMS.43

Aspiration IMS. Another type of IMS used to detect CWAsis aspiration IMS (AIMS). The ionization occurs at ambientconditions in the presence of a relatively high amount of water,which affects the kinetics of ionization reactions. The principle ofoperation of the AIMS instrument is depicted in Figure 3. Ionstravel through an orthogonal electric field in which they aredeflected to multiple channels located on the collecting electrode.Ions with a faster velocity collide earlier than slower ions; thedetection in AIMS is based on characteristic signal patterns andutilizes pattern recognition methods. A Finnish company, Envi-ronics Oy, is a specialized manufacturer of the ChemPro handheldAIMS instrument.

AIMS has a direct interface with ambient air with flow-throughconstruction, allowing very fast response and recovery times. Theinstrument does not have a shutter grid and is typically operatedwithout any membranes or dopants. The detection process iscontinuous; the flow rate is 1-2 L min-1 with detection levels ofppb or sub-ppb for CWAs. Furthermore, AIMS instrumentsdiffer from conventional devices by detecting the spatialdistribution of the ion flow. The polarity of the electric field is

alternated continuously, thus ions of both polarities areseparated and detected simultaneously. To improve selectivity,the electric field can be adjusted individually for each electrodepair.

The main advantages of this technology are that it has veryhigh sensitivity and can potentially be miniaturized and massproduced. The devices are also simple and sufficiently ruggedfor in-field use. Its sensitivity is easily adjusted because itsionization efficiency is flow rate dependent. Furthermore, thedetection limits approximately correspond to toxicity values; AIMSprovides a sensitive and specific output for highly toxic chemicalvapors.44 The next generation, so-called “2nd order AIMS” (orion focusing AIMS), uses rapidly-sweeping electrical fields tocreate a large number of virtual channels. The ions are focusedinto the sample stream by means of an electric field or, more often,by controlled flow streams. This construction improves detectionby improving ion separation.

AIMS has been used to characterize the degradation productsof soman and VX,45 and the detection performance of AIMSdevices has been investigated with CWAs and simulants.46 Also,a miniaturized ion-focusing aspiration condenser-type IMS instru-ment has been used to detect various CWAs.47 In addition, thetoxic industrial chemicals ethyl parathion and toluene 2,4-diiso-cyanate have been analyzed.48

Field Asymmetric IMS. The mechanism of field asymmetricIMS (FAIMS), also known as differential mobility spectrometry(DMS), is closely related to AIMS, but the ion separation processdiffers. In FAIMS, ions pushed by the gas flow travel through aperpendicular electrical field. The electrical field is generated byan asymmetric AC dispersion voltage but also has a compensationvoltage called the DC component. This radio-frequency (RF)region works as a filter, and ions of both polarities are collectedbehind it. Ion mobility is a function of field strength, especially inthe case of high fields; hence, ion drifts caused by the asymmetricfield can be compensated for with a suitable compensation voltage.The advantages of this instrument are its small and simpleconstruction and potentially high resolution. Detection is basedon the signal peak position and intensity in the RF-voltage-Compensation Voltage (Vrf-CV) plane. The principle of FAIMSion separation is shown in Figure 4. The electric field is appliedto the lower plate while the upper plate is grounded. Ion B reachesthe detector while ions A and C stick to the plates. By adjustingthe compensation voltage, different ions (A or C) will reach thedetector.

Currently, technical development in the IMS field is mostlyfocused on FAIMS. One important feature is miniaturization: thefabrication and characterization of a micro-electro-mechanical-system (MEMS) radio-frequency ion mobility spectrometer (rf-

Figure 3. The operating principle for an AIMS instrument.

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IMS) having high resolving power has been described.49-51 Themajor commercial source of FAIMS instruments is ThermoScientific. In addition, General Dynamics offers a commercialhandheld FAIMS device. Owlstone manufactures miniaturizedFAIMS microchips, as depicted in Figure 5.

FAIMS has been used to detect nerve and blister agentsimulants,52 various CWAs,53 and organophosphorus com-pounds.54 A comprehensive review including a summary of thebasics together with a consideration of various applications ofFAIMS has been recently published.55

FUTURE PROSPECTSRelationship to MS. The combination of IMS with other

detection techniques has become increasingly important. One grow-ing trend is to unite IMS with MS. In this combination, so calledIM/MS, the ion mobility section serves as a pre-separation phaseprior to MS analysis, enabling a second dimension of separation. IM/MS can separate conformers, isomers, or chiral molecules with thesame molecular mass, thus improving analytical performance.56 ESIIM/MS instrument parameters for the analysis of CWAs have beenoptimized.57 Other combinations that are already used are GC orLC with IMS. Waters manufactures commercial Q-TOF instrumentsthat can have an IMS section incorporated.

Recent developments with ambient pressure MS also comeclose to the principles and applications of IMS. These methods

include, for example, desorption electrospray ionization (DESI)58

and direct analysis in real time (DART)59 MS. Similarities includeionization at ambient pressure, sampling from surfaces, water-assisted ionization, and portability. When water is used as thesolvent, the sprayed water molecules form hydronium ions in thepresence of an electric field. The sample molecules are bombardedby these hydronium ions; the ionization occurs via proton transferfrom the hydronium ion to the sample molecule. These andvarious other atmospheric pressure ionization techniques couldfunction as ion sources and sample introduction devices forcompounds having low or nonexistent volatility.

Currently, the smallest MS instrument with an external DESIsource, the Mini 11, has dimensions of 22×12×18 cm and weighs5 kg with batteries;60 it is noticeably smaller than its predecessor,the Mini 10 (shoebox-sized, 32×22×19 cm, 10 kg).61 Even thoughthe Mini 11 is still fairly big when compared to handheld IMSinstruments, it shows that the drive towards miniaturized massspectrometers continues. This is also a challenge to standaloneIMS devices because the analytical power of MS is superior. Onthe other hand, this trend should eventually produce a handheldcombined IM/MS instrument. A recently published article de-scribes the design of a prototype field-portable IM/MS instru-ment.62

Instrument Development. Any novel technology for CWAdetection must fulfill the requirements for the detection of CWAs,and the same instrument should be able to detect toxic industrialchemicals and potentially, yet to be determined non-traditionalagents too. Further improvements in IMS will probably includelower detection limits, enhanced selectivity, faster operation,standardized libraries that enable comparisons between labora-tories, and overall enhanced instrument performance. The per-formance development is achievable with combinations of differentmeasurement techniques using variations on IMS such as FAIMSwith conventional drift or FAIMS with aspiration IMS. Also,instrument performance can be improved with the developmentof sampling and sample pre-treatment methods. On the otherhand, the ongoing trend toward combining IMS with otheranalytical techniques like MS and GC will continue. EventuallyIMS will be a standard part of a hybrid instrument.

Another area that will likely have an impact on IMS is thedevelopment of future technologies, presumably including ad-vanced manufacturing processes like nanotechnology, microme-chanics, and semiconductor technology applied to production ofnon-radioactive ionization systems and sensor structures, includingthose that are integrated with other types of gas sensors. All these

Figure 4. The operating principle for a FAIMS instrument.

Figure 5. Top) Micromachined FAIMS. Reprinted with permissionfrom Miller, Eiceman, Nazarov & King (2000), copyright 2000 Elsevi-er.50 Bottom) FAIMS microchip placed on fingertip. Photo courtesyof Owlstone, used with permission.

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technologies will facilitate the manufacturing of remarkably smallbut complex systems leading to miniaturized “button-size” lab-on-a-chip personal detectors. However, a great deal of develop-mental research work is required for this. Presumably theseinstruments will become technically feasible before they arecommercially sensible. This may be a limiting factor for newdesigns; thus near- or mid-future devices will be based on moretraditional, relatively low investment manufacturing techniques.

From the user’s perspective, a low training burden and lowlifetime costs are also considerations for instrument development.Any additional or complicated user interface is also a drawback.Therefore, current development is focusing on separating theactual measuring instrument and the user interface. Furthermore,forms of mobile communication provide novel possibilities suchas networked sensor systems and personal information sources.When interfaces are separated from measurement devices, therehas to be a central unit that collects and combines the informationoriginating from real-time measurement devices. This contributesto the technical development of easy-to-use, multipurpose, andmultifunctional detection devices.

There exist application-driven ideas to improve and develop IMS-based instruments even further. These include a disposable IMSanalyzer for respiratory air quality monitoring as a separate deviceor attached to a personal gas mask. Continuous monitoring ofstockpiled industrial chemicals and public infrastructures is possibleby integrating IMS with ventilation systems. Another possibility isto use multiple parallel IMS instruments to produce an atmosphericpressure reactor chamber where reaction products are separatedfrom reactants and enriched using ion mobility principles.

SUMMARYEven though IMS technology has some disadvantages, the numerousadvantages show that IMS is currently the favored state-of-the-arttechnology for detection of CWAs. The need for a rugged, easy-to-operate, sensitive, and reliable instrument for in-field use continues.In urban environments, the monitoring and detection of CWAs andtoxic industrial chemicals play important roles in public safety. Inaddition, industrial methods that enable surveillance and fast warn-ings to detect leakage of hazardous chemicals or environmentalpollutants are needed. In the future, IMS technology either alone orcombined with other detection technologies will enable practicaldetection of CWAs and hazardous chemicals.

ACKNOWLEDGMENTFunding by the Finnish Funding Agency for Technology and

Innovation (TEKES) is acknowledged. Dr. Mary Metzler isthanked for language revision.

Osmo Anttalainen is a Vice President of Technology at Environics Oy andhas been involved in IMS sensor development since 1994. Marko Makinenis researcher focused in IMS, gas-phase chemistry, and environmentalpollutants. Mika Sillanpaa is professor and head of the Laboratory of AppliedEnvironmental Chemistry. His interests include environmental analysis andtechnologies in environmental engineering. Address correspondence to Maki-nen at Laboratory of Applied Environmental Chemistry, Department ofEnvironmental Science, University of Eastern Finland, Patteristonkatu 1,50100 Mikkeli, Finland; marko.makinen@uef.fi; +358-40-355 3713 (phone);+358-15-355 6363 (fax).

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