Anal. Chem. 2010, 82, 9594–9600
Ion Mobility Spectrometry and Its Applications in Detection of Chemical Warfare Agents Marko A. Ma¨kinen University of Eastern Finland Osmo A. Anttalainen Environics Oy (Finland) Mika E. T. Sillanpa¨a¨ Lappeenranta University of Technology and University of Eastern Finland MR. TIMO SILONSAARI
When fast detection of chemical warfare agents in the field is required, the ion mobility spectrometer may be the only suitable option. This article provides an essential survey of the different ion mobility spectrometry detection technologies. (To listen to a podcast about this feature, please go to the Analytical Chemistry multimedia page at pubs. acs.org/page/ancham/audio/index.html.) The threat of weapons of mass destruction (WMDs), such as chemical warfare agents (CWAs) and toxic industrial chemicals, is of great concern worldwide. This menace makes it necessary to detect the presence of such weapons in both military and civil environs. Toxic chemicals are used in large quantities by industry, and the information needed to synthesize them has become more accessible through the Internet. In addition to providing protection from chemical attacks, fast detection is needed to detect possible chemical leaks which may occur during accidents, disposal, or dumping. 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 mobility spectrometry (IMS) technologies can be applied to the detection and identification of these chemicals. The properties of the most common CWAs are described, and the principles, limitations, and advantages of analytical IMS detection together with its future prospects are discussed. INTRODUCTION TO CHEMICAL WARFARE AGENTS Toxic chemicals have great potential to inflict significant casualties, thus chemical weapons are classified as WMDs. Furthermore, 9594
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CWAs are easy to disguise and are practically imperceptible, thus making them easy to use against the public. CWAs are mostly dispersed as vapors or aerosols; the more volatile the agent is, 10.1021/ac100931n 2010 American Chemical Society Published on Web 10/27/2010
the faster it evaporates and disperses. In addition, CWAs or their degradation products may linger as soil contaminants. Structures of common CWAs are shown in Figure 1. Earlier articles have evaluated the different technologies for detection of CWAs.1,2 Classification of CWAs. CWAs are divided into five different categories.3,4 i) Vesicating and blistering agents such as sulfur and nitrogen mustards cause extensive and irreversible tissue damage. Lewisite is the most infamous of the organoarsenic warfare agents. ii) Choking agents or pulmonary intoxicants are, for example, phosgene, which does not detoxify naturally, has a cumulative effect, and may persist in sheltered areas or buildings for a long time and chlorine, which at moderate concentrations is a weak pulmonary irritant but in high concentrations is extremely lethal. Both are also indispensable industrial chemicals. iii) Nerve agents are organophosphonates, which are further divided into three subcategories: G agents (G denotes German origin), such as Tabun (GA), Sarin (GB), and Soman (GD); V agents (mainly VX; some variants exist); and Novichok agents. Tabun was initially used as a pesticide but has been utilized for military purposes. Sarin is an extremely volatile colorless liquid that has a mild aroma of rotting fruit if impure. Soman is more poisonous than the two aforementioned and has a camphor-like odor if impure. VX is an odorless liquid with an appearance similar to motor oil. Novichoks are considered to be the most hazardous agents ever made.5 iv) Blood-born agents are cyanogens such as HCN and CNCl. They are distributed by the vascular system. v) Incapacitating agents are non-lethal CWAs. CS (tear gas) is widely used for various purposes. In addition, some nations are producing, stockpiling, and transporting large quantities of toxic industrial chemicals. ION MOBILITY SPECTROMETRY Principles. IMS involves both ionization of the sample and analysis of the ions formed at ambient temperature and at ambient or reduced pressure. This analytical method is used in various demanding applications including field or on-site detection of vapor phase species such as chemical weapons, explosives, and drugs. The first analytical device was introduced in the late 1960s,6 and CWA detectors were introduced in the 1970s and early 1980s.7 At atmospheric pressure, the ion-molecule reactions of CWAs result 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 the detection of trace CWAs and explosives.9 Recently, appreciation of the IMS technique and its various applications has increased.10 IMS instruments are widely used by military, security, customs, and border authorities. The majority of the commercial instruments are used for explosives detection,11
Figure 1. Structures of some typical CWAs.
and probably the most noticeable application is the walk-through portals in airports used to monitor for traces of explosives.12 In IMS, gas phase ions are created by ionizing neutral molecules using photon, corona, flame, ESI, or radioactive ionization. Most of the instruments use radioactive ionization sources like 63Ni or 241Am because they are simple, convenient, and stable. The ions produced are separated by their different velocities through a drift gas in an electric field. IMS separation is based on ion mobility, with the relationship between ion velocity and electric field depending on the ion’s weight, charge, and shape.11 The temperature, pressure, and molecular properties of the drift gas also play important roles.13 To remove background interference and improve sensitivity and selectivity, additional reagent gases (dopants) can be used to create 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 pressure has its own pros and cons. In case of CWAs, the instruments mainly operate in positive mode; i.e., the ions formed from the samples are positively charged. However, some exceptions exist because agents with halogen atoms and low proton affinity are unable to form stable positively charged ions. Advantages and Limitations. There are many CWA detection techniques. For example, common laboratory methods and instruments such as GC, LC, CE, and MS, individually or in combination, may be used. On-site screening techniques include surface acoustic wave (SAW), electrochemical, and spectrophotometric sensors. All these techniques have their pros and cons; for example, SAW sensors can be small and portable but are sensitive to moisture and may suffer from de-wetting effects that reduce responsiveness.15 Spectrophotometric techniques are based on color change reactions (detection papers or detection tubes) or emission lines (flame photometric detection [FPD]). Color change experiments are easy to perform but need a relatively high amount of sample, can be time consuming, and give ambiguous results. FPD is fast and sensitive but produces false positives. Typical drawbacks to all these techniques are false positives and adsorption of the agents onto instrument surfaces.2 However, IMS also suffers from these disadvantages. IMS as an analytical technique has several specific weaknesses. The primary drawbacks are its low resolving power, limited selectivity,16 and the experimental nature of the technique. Matrix effects such as humidity, temperature, and the composition of the sample may influence the detector’s response. Ideally, IMS should be used in environments with controlled temperature, low humidity, and controlled amounts of dopants, thus requiring delicate engineering and parameter optimization for in-field use. The separation of ions is highly dependent on ion mobilities in a drift gas under the influence of an electric field, which may be affected by altering the polarizability and mass of the drift gas, thus changing the chemistry of ion-neutral molecule interactions. Selectivity could be improved by adjusting the electric field strength and drift tube pressure or temperature; other ions may also be examined. Nonetheless, high collision rates at atmospheric pressures could be advantageous in IMS. Based on the thermodynamic equilibrium between the ions and the neutral molecules, IMS is able to selectively ionize whole classes of compounds with Analytical Chemistry, Vol. 82, No. 23, December 1, 2010
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Figure 2. The operating principle for a conventional IMS instrument.
collectively unique thermodynamic properties such as high proton affinity. Another drawback of IMS chemical interference in highly contaminated environments. Such interference may be reduced by using highly selective forms of ionization with additional reagent molecules.16 However, if the measurements are made at high pressures in which gas-phase collisions may increase the frequency of the charge exchange reaction, the desired selectivity cannot be achieved.17 False positives also may pose a problem. Some well-known examples of interferant cross-references in explosive trace detection include certain medications such as vasodilators containing nitroglycerin, certain ingredients in commonly-used hand lotions, cardamom, and certain types of firefighting foams. These problems may be efficiently solved with instrumental combinations like IM/MS, which could significantly decrease the potential for false positive responses when screening for CWAs.18 IM/MS has already been used to analyze CWAs in spiked food products.19 The bureaucracy involved in using radioactive sources, including complying with numerous ordinances and licensing requirements, is also a limitation. Alternative, non-radioactive atmospheric pressure ionization methods include photoionization, laser ionization, corona discharge, and surface ionization. However, nonradioactive ionization sources suffer from limited lifetimes, aging, stability, and the need for power. Even though IMS has the above-mentioned drawbacks, numerous advantages tip the balance in its favor. The main advantages of IMS are instrumental simplicity, small size, light weight, portability, reliability, ease of operation, real time monitoring capability, fast response, short analysis time, low power consumption, low operating cost, and high sensitivity, specifically for persistent CWAs.20 The analytical performance of IMS is superior to that of other CWA detection methods. Analysis and response times of IMS are very short, thus providing the basis for a real-time monitoring capability: the actual ion separation time in one scan is on the millisecond timescale, and total measurement time is only a few seconds. Common agents are easy to ionize and to analyze, leading to relatively high reliability and sensitivity. Combining IMS with other analytical instruments such as GC and MS further increases the analytical power. These combinations provide a second dimension of separation, which increases selectivity and therefore reduces the number of false positives. An example is an analysis of TNT in which hand lotion can produce a false positive. Both substances produce equal signals in IMS and in MS but are 9596
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distinct in a 2D spectrum.21 This IM/MS combination can also be used to analyze degradation products of CWAs from a complex aqueous mixture.22 Other advantages originate from user-friendliness and practical details. Instrumental simplicity and ease of use creates a large network of potential users by simplifying training. The small size and weight allows true portability. Easy maintenance and low power consumption together with robustness enable IMS usage in difficult environs such as those required for military applications. TECHNIQUES IN CHEMICAL WARFARE AGENT DETECTION Conventional IMS. A conventional ion mobility spectrometer consists of the reaction region, including the ion source and ion gate, and the drift region and detector. The sample compounds are ionized by proton transfer or electron capture reactions. The electronic gating grid (ion gate) introduces the ions into the drift region, where the ions travel along the electric field gradient. The ions are separated according to their velocities in the neutral, counter-flowing drift gas. Ions create a drift time related signal through collision and neutralization at the detector (a Faraday plate). The operating principle for a conventional IMS device is presented in Figure 2. Detection in conventional IMS is based on signal peak position and intensity. The selectivity is defined by resolving power, which in turn is defined by drift time per peak half width. In general, the length of the drift tube limits the selectivity, but advanced signal processing methods like FT may resolve this problem. Conventional IMS is difficult to miniaturize, so only a few manufacturers are fabricating handheld devices. Nevertheless, the majority of the instruments used for in-field detection are based on this conventional separation and detection technique. The current commercial manufacturers of conventional handheld IMS instruments for in-field detection include Smiths Detection, Bruker Daltonics, IUT GmbH, and GE Security. Conventional IMS instruments have been widely used in CWA investigations. The early studies included pesticides,23 organophosphorus compounds,24 sarin,25 various phosphorus esters including G nerve agents,26 and methyl isocyanate.27 More recently, research in Hill’s group has been especially active. They have analyzed the reduced mobility values of various CWA simulants and degradation products.28,29 The combination of ESI and IMS has been used to characterize CWA degradation products, with detection limits
