Engineering Aviation Security Environments—Reduction of False Alarms in Computed Tomography-Based Screening of Checked Baggage (2013)

Below is the uncorrected machine-read text of this chapter, intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text of each book. Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.

C Chemistry-Based Alternatives to Computed Tomography-Based Explosives Detection SOME LIMITATIONS OF CT X-RAY METHODS Methods of detection for explosives based on computed tomography (CT) are fundamentally imaging—rather than chemical—analysis and provide very little molecular information. The measurement provides low-dimensional, cross-sectional images, and the detection depends mainly on density, which is a single number. While some variants of x-ray methods such as dual-energy systems provide elemental information, that information remains limited and the technology has not been widely adopted. It is conceivable that one could manipulate non-explosive materials to get the same output as given by an explosive. GENERAL REQUIREMENTS FOR ALTERNATIVE TECHNOLOGIES TO COMPUTED TOMOGRAPHY-BASED EXPLOSIVES DETECTION Any technology developed to augment or replace CT for explosives detection must be molecule- specific because explosives have a wide variety of chemical structures, some of which are very similar to an even larger class of non-explosive materials, and may, moreover, be present in mixtures that have responses different from those of pure explosives. Additional criteria for such an alternative technology are these: • High sensitivity, • Rapid analysis, • Greater specificity than merely sensing, • Capable of being deployed in a standoff manner • Employing automatic (rather than manual) sampling ALTERNATIVES TO CT X-RAYS Among the technologies that meet some, if not all, of the criteria listed in the preceding section are the following: • Dual energy CT. Offers a second cross section that provides both density and atomic number but not molecular information • Neutron activation, x-ray fluorescence. Provides elemental information, but not molecular information; it can be deployed in a stand-off manner and can penetrate objects. NOTE: This appendix was independently authored by Graham Cooks, committee member, with the endorsement of the rest of the committee. 73 

• Ion mobility spectrometry (IMS). 1 Is attractive for its sensitivity, simplicity, ruggedness, and reliability but is limited in terms of the quality of the molecular information provided and consequently in molecular specificity. More recent work allows explosives recognition by library comparison but still not with high specificity. 2 There is still a great need for approaches that are more molecule-specific, and the combination of IMS with mass spectrometry is one possibility. Supplementary data gained from treatment with reactive gases is another. Mass spectrometry (MS) and tandem mass spectrometry 3 are another option, which is discussed in greater detail in the section that follows. MASS SPECTROMETRY MS is a method of determining the masses of particles, the elemental composition of a sample or molecule, and the chemical structures of molecules. MS does this by ionizing chemical compounds to generate charged molecules or molecular fragments and then measuring their mass-to-charge ratios. In a typical MS procedure, 1. A sample is loaded onto the MS instrument and undergoes vaporization, 2. The components of the sample are ionized, which results in the formation of charged particles, 3. In an analyzer, electromagnetic fields separate the charged particles on the basis of their mass-to-charge ratio. 4. The charged particles are detected, usually by a quantitative method, and 5. The charged particles’ signal is processed into mass spectra. Instruments for performing mass spectrometry consist of three modules: • An ion source, which converts gas-phase sample molecules into ions. • A mass analyzer, which employs electromagnetic fields to sort the ions on the basis of their masses. • A detector, which provides data for calculating the quantity of each ion present based on the measured value of an indicator amount. The potential of MS in aviation security applications was described in the 2004 report of the NRC Committee on Assessment of Security Technologies for Transportation, Opportunities to Improve Airport Passenger Screening with Mass Spectrometry. In that report the committee’s focus was MS’s potential in explosives trace detection (ETD) to resolve false alarms raised by explosives detection systems. The limitations and advantages of this technology—as well as advances that have taken place since that report’s publication—are described in the sections that follow. 1 G.A. Eiceman and Z. Karpas, Ion Mobility Spectrometry, 2nd ed., CRC Press, Boca Raton, Fla., 2005. 2 See, for example, D.S. Levin, R.A. Miller, E.G. Nazarov, and P. Vouros, Rapid separation and quantitative analysis of peptides using a new nanoelectrospray-differential mobility spectrometer-mass spectrometer system, Analytical Chemistry 78:5443-5452, 2006; and R.W. Purves, R. Guevremont, S. Day, C. Pipich, and M.S. Matyjaszczyk, Mass spectrometric characterization of a high-field asymmetric waveform ion mobility spectrometer, Review of Scientific Instruments, 69:4094-4105, 1998. 3 In tandem mass spectrometry the ions are subjected to two or more analyses, separated either by space or time. 74 

Some Limitations of Mass Spectrometry Mass spectrometry for explosives detection is attractive in principle when coupled with new ambient ionization methods, for tandem mass spectrometry (MS/MS) and a small, possibly even handheld, mass spectrometer. However, the technology also has a number of limitations: • It is not normally deployed in a stand-off manner, • The trace analysis method is not suited to bulk examination, • Representative sampling is very difficult, • It may be possible to defeat the system by using overwhelming chemicals, • Quantitation of solids is difficult because of the need for an internal standard, and • Absolute quantitation methods are not very successful. One question is where to best apply the technology. Opened bags sent for secondary screening may be most appropriate. In spite of these limitations and open questions, there have been very significant advances in MS since the NRC 2004 report Opportunities to Improve Airport Passenger Screening with Mass Spectrometry. These are discussed in the following section. Recent Developments in Mass Spectrometry Ambient Ionization Ambient ionization refers to a family of methods developed since 2004, in which samples are ionized in their native environment and original physical state without needing to be prepared by transferring analyte ions from near the surface of the sample into the vacuum system of the mass spectrometer. Several dozen ambient ionization methods have been described and reviewed in the recent literature.4 The methods can be divided into those based on sprays of charged droplets and those based on plasmas or lasers. Desorption of material from the sample surface and ionization of that material are the two operations common to all methods. In some cases, such a desorption electrospray ionization (DESI) 5 and direct analysis in real time (DART), 6 the desorption and ionization steps are achieved by a single agent (charged droplets in DESI, gaseous metastable atoms and ions in DART). In other cases, independent methods are used to effect these two steps, as in laser ablation electrospray ionization, 7 in which a laser is used for desorption, and an electrospray to ionize the desorbed molecules in the gas phase. Some of these recent developments are illustrated in Figure C-1. 4 R.G. Cooks, Z. Ouyang, Z. Takats, and J.M. Wiseman, Ambient mass spectrometry, Science 311:1566-1570, 2006; G. Van Berkel, Established and emerging atmospheric pressure surface sampling/ionization techniques for mass spectrometry, Journal of Mass Spectrometry 43:1161-1180, 2008. 5 Z. Takats, J.M. Wiseman, B. Gologan and R.G. Cooks, Mass spectrometry sampling under ambient conditions with desorption electrospray ionization, Science 306:471-473, 2004. 6 R.B. Cody, J.A. Laramee, and H.D. Durst, Versatile new ion source for the analysis of materials in open air under ambient conditions, Analytical Chemistry 77:2297-2302, 2005. 7 P. Nemes and A. Vertes, Laser ablation electrospray ionization for atmospheric pressure, in vivo, and imaging mass spectrometry, Analytical Chemistry 79:8098-8106, 2007. 75 

FIGURE C-1 Some of the several dozen ambient ionization methods developed in the past few years. SOURCE: Courtesy of R.G. Cooks, Purdue University, as described in the following: DESI: Adapted from Z. Takáts, J.M. Wiseman, B. Gologan, and R.G. Cooks, Mass spectrometry sampling under ambient conditions with desorption electrospray ionization, Science 306(5695):471-473, 2004; ELDI: J. Shiea, M.-Z. Huang, H.-J. HSu, C.-Y. Lee, C.- H. Yuan, I. Beech, and J. Sunner, Electrospray-assisted laser desorption/ionization mass spectrometry for direct ambient analysis of solids, Rapid Communications in Mass Spectrometry 19:3701-3704, 2005; MALDESI: J.S. Sampson, A.M. Hawkridge, and D.C. Muddiman, Generation and detection of multiply-charged peptides and proteins by matrix-assisted laser desorption electrospray ionization (MALDESI) Fourier transform ion cyclotron resonance mass spectrometry, Journal of the American Society for Mass Spectrometry 17(12):1712-1716; EDI: K. Hiraoka K. Mori, and D. Asakawa, Fundamental aspects of electrospray droplet impact/SIMS, Journal of Mass Spectrometry 41(7):894-902, 2006; AP-MALDI: V.M. Doroshenko, V.V Laiko, N.I. Taranenko, V.D. Berkout, and H.S. Lee, Recent developments in atmospheric pressure MALDI mass spectrometry, International Journal of Mass Spectrometry 221(1):39-58, 2002; DART: R.B. Cody, J.A. Laramée, and H.D. Durst, Versatile new ion source for the analysis of materials in open air under ambient conditions, Analytical Chemistry 77(8):2297-2302, 2005. Among the recent plasma-based methods are those that are based on discharge barrier desorption ionization (DBDI), 8 a method that produces low-power, stable radio frequency plasmas in air or a noble gas. The low-temperature plasma (LTP) probe is a recent version of non-thermal (non-equilibrium) plasma. 9 The characteristic feature of this probe configuration is that it allows the plasma direct access to the sample’s surface and near surface. Gas flows are minimal, and total power required is very low (around 3 W). Voltages used are in the kV range and frequencies in the kHz range. The method shows promise as an ionization method complementary to DESI: It ionizes many small molecules, including explosives, and generates mass spectra characterized by abundant molecular ions from which molecular weights are obtained and from which MS/MS spectra can be recorded showing characteristic fragment ions for compound identification. 8 N. Na, M.X. Zhao, S.C. Zhang, C. Yang, and X. Zhang, Development of a dielectric barrier discharge ion source for ambient mass spectrometry, Journal of the American Society for Mass Spectrometry 18:1859-1862, 2007. 9 J.D. Harper, N.A. Charipar, C.C. Mulligan, X. Zhang, R.G. Cooks, and Z. Ouyang, Low-temperature plasma probe for ambient desorption ionization, Analytical Chemistry 80:9097-9104, 2008. 76 

A) B) FIGURE C-2 (A) Negative ion DESI mass spectrum showing the formation of the Meisenheimer complex between TNT and the methoxide anion at m/z 258 when examining 10 pg of TNT deposited on paper in a total area of 1 cm2. (B) negative ionization of 100 ng RDX by LTP; inset shows the nitrate cluster anion formation during LTP ionization in air. SOURCE: After I. Cotte-Rodriguez, Z. Takats, N. Talaty, H. Chen, and R.G. Cooks, Desorption electrospray ionization of explosives on surfaces:  Sensitivity and selectivity enhancement by reactive desorption electrospray ionization, Analytical Chemistry 77:6755-6764, 2005. The most extensive studies of ambient ionization of explosives have employed DESI. The more recent LTP method—like other plasma methods, including DBDI and plasma assisted-desorption ionization (PADI) 10—is also attractive for explosives analysis so DESI and LTP are almost exclusively discussed in what follows. Both LTP 11 and DESI 12 allow nanogram amounts of explosives to be detected from ambient surfaces and characterized by highly specific MS/MS data in times on the order of a few seconds. Some typical data recorded using a commercial mass spectrometer are shown below for trinitrotoluene (TNT) and a peroxide explosive using DESI (Figure C-2). The absence of a need for sample preparation in ambient ionization mass spectrometry means that high throughput can be achieved; most measurements take only a few seconds, including the time to confirm a compound seen in the mass spectrum as a characteristic ion through its MS/MS spectrum. Moreover, the low-impact nature of DESI and other methods of ambient ionization means that the mass spectra are dominated by intact molecular ions. The specific identification of materials as particular chemical entities is arguably more important and more difficult than achieving the speed and sensitivity necessary for airport security detection purposes. This is in fact widely recognized as the main problem with ion mobility, which is fast and sensitive but not highly specific. In MS experiments, additional specificity is easily provided by MS/MS and in larger instruments by high-resolution measurements that give molecular formulas. Specificity can be increased further by another simple experiment, a “reactive” version of ambient ionization. These 10 L.V. Ratcliffe, F.J. M. Rutten, D.A. Barrett, T. Whitmore, D. Seymour, C. Greenwood, Y. Aranda-Gonzalvo, S. Robnison, and M. McCoustra, Surface analysis under ambient conditions using plasma-assisted desorption/ionization mass spectrometry, Analytical Chemistry 79:6094, 2007. 11 J.D. Harper, N.A. Charipar, C.C. Mulligan, X. Zhang, R.G. Cooks, and Z. Ouyang, Low-temperature plasma probe for ambient desorption ionization, Analytical Chemistry 80:9097-9104, 2008. 12 I. Cotte-Rodriguez, Z. Takats, N. Talaty, H. Chen, and R.G. Cooks, Desorption electrospray ionization of explosives on surfaces:  Sensitivity and selectivity enhancement by reactive desorption electrospray ionization, Analytical Chemistry 77:6755-6764, 2005; Z. Takats, I. Cotte-Rodriguez, N. Talaty, H.W. Chen, and R.G. Cooks, Direct, trace level detection of explosives on ambient surfaces by desorption electrospray ionization mass spectrometry, Chemical Communications 1950-1952, 2005. 77 

experiments are done by simply adding a chemical reagent to the spray solution (DESI) or the support gas (LTP). For example, betaine aldehyde (BA) gives characteristic adducts with TNT during the DESI process when BA is incorporated in the spray solvent (Figure C-3). FIGURE C-3 Positive mode electrospray ionization mass spectrum acquired by spraying TNT sample with betaine aldehyde (BA) in methanol water. SOURCE: Data from Chumping Wu and R.G. Cooks. Handheld Mass Spectrometers The miniaturization of mass spectrometers is moving forward swiftly. 13 Some of the work deals only with the actual mass analyzer, but full, autonomous miniature MS systems are also in operation. Table C-1 summarizes Ouyang and Cooks’ 14 information on the state-of-art in miniature mass spectrometers. Note that MS/MS capabilities are highly desirable for trace mixture analysis of explosives. In addition, ambient ionization is needed for rapid analysis. Both the DESI and LTP ionization techniques have been implemented on portable ion-trap mass spectrometers. Pulsed ion introduction—discontinuous atmospheric pressure introduction (DAPI) 15—is essential for performing atmospheric pressure ionization, including ambient ionization because of the small pump sizes. Negative ions are detected by incorporation of a conversion dynode in conjunction with a channeltron electron multiplier detector. Current efforts focus on optimization of ion transport in these experiments, which remain inefficient in spite of ability to detect subnanogram amounts of explosives using benchtop instruments. Most losses are in the atmospheric pressure region and involve failure to efficiently transport the atmospheric pressure ions/ionized droplets into the mass spectrometer. 13 Z. Ouyang and R.G. Cooks, Miniature cylindrical ion trap mass spectrometer, Analytical Chemistry 74(24):6145-6153, 2002. 14 Zheng Ouyang and R. Graham Cooks, Miniature mass spectrometers, Annual Review of Analytical Chemistry 2:187-214, 2009. 15 L. Gao, R.G. Cooks, and Z. Ouyang, Breaking the pumping speed barrier in mass spectrometry: discontinuous atmospheric pressure interface, Analytical Chemistry 80:4026-4032, 2008. 78 

TABLE C-1 Self-Sustainable Portable MS Systems a MIMS membrane introduction mass spectrometry; GDEI glow discharge electron impact ionization; APCI atmospheric-pressure chemical ionization; ESI electrospray ionization; SPME solid-phase microextraction. SOURCE: Adapted from Z. Ouyang, and R.G. Cooks, Miniature mass spectrometers, Annual Review of Analytical Chemistry 2:187-214, 2009. The issue of large area detection 16 has been addressed also in benchtop instruments but not in miniature MS instruments. Larger areas (several hundred square centimeters) are accessible by LTP methods using several plasma probes. Comparable DESI experiments involve large amounts of solvent and are more awkward to implement. Stand-off detection experiments have been surprisingly effective. Ions are transported back to the mass spectrometer over distances of several meters in both DESI and LTP experiments. Signals fall over several orders of magnitude in these experiments, but chemical noise falls faster, and high-quality explosives data can be recorded on benchtop lab instruments for samples of a few nanograms. Supplementary pumping greatly improves performance. The combination of large area detection and stand-off detection will be difficult to achieve, and neither kind of detection is easily achieved in miniature instruments. The power of handheld mass spectrometers is illustrated by the fact that they can be used to perform multiple-stage MS experiments. Such experiments add great specificity to identifications made by MS and usually require little extra time to perform. The relevant capabilities of the combination of miniature mass spectrometer and ambient ionization are illustrated in Figure C-4, which shows LTP and DESI spectra taken on small amounts of sample with these methods. 16 Santosh Soparawalla, Gary A. Salazar, Ewa Sokol, Richard H. Perry, and R. Graham Cooks, Trace detection of explosives distributed over large areas using mass transfer and ambient ionization mass spectrometry, Analyst 135:1953-1960, 2010. 79 

FIGURE C-4 Use of DESI and LTP ambient ionization methods to detect compounds in ordinary materials. ADVANTAGES OF MASS SPECTROMETRY IN TRACE EXPLOSIVES ANALYSIS It is clear from the data collected here that a new generation of mass spectrometers has already emerged in research labs with capabilities that are potentially applicable to airport screening of baggage and passengers. Among the favorable characteristics of these instruments are their small size and the highly capable ambient ionization methods, which are rapid and sensitive and yet give a great deal of specific information on the chemical nature of a particular sample, including information on the presence of traces of explosives on surfaces. Other characteristics, like the ability to perform stand-off MS detection, the ability to add specificity by “reactive” ionization methods, the ability to quantify, and the ability to extend the methodology to surfaces with large areas are less well developed but are under study. While the direct analysis of surfaces for explosives is the simplest and most desirable implementation of these capabilities, the swabbing of surfaces with the standard “swiffer” wipes used in security lines today could also be used in secondary passenger and baggage screening, and it could be done by DESI MS with much greater chemical specificity (fewer false positives) than when done by ion nobility. 80