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Article Cite This: Anal. Chem. XXXX, XXX, XXX−XXX

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Development of Ion Mobility Spectrometry with Novel Atmospheric Electron Emission Ionization for Field Detection of Gaseous and Blister Chemical Warfare Agents Yasuo Seto,*,†,∥ Ryota Hashimoto,†,⊥ Takashi Taniguchi,† Yasuhiko Ohrui,†,⊥ Tomoki Nagoya,†,@ Tadashi Iwamatsu,‡ Shohei Komaru,‡ Daisuke Usui,‡ Satoshi Morimoto,‡ Yasuhiro Sakamoto,‡ Atsushi Ishizaki,§ Tatsuhiro Nishide,§ Yoko Inoue,§ Hiroaki Sugiyama,§ and Nobuo Nakano§ †

National Research Institute of Police Science, 6-3-1 Kashiwanoha, Kashiwa, Chiba 277-0882, Japan Business Solutions BU, Advanced Technology Development Unit, Sharp Corporation, 492 Minosho-cho, Yamatokoriyama, Nara 639-1186, Japan § RIKEN KEIKI Co., Ltd., 2-7-6 Azusawa, Itabashi, Tokyo 174-8744, Japan

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‡

S Supporting Information *

ABSTRACT: Drift tube ion mobility spectrometry with a novel atmospheric electron emission (AEE) source was developed for determination of gaseous and blister chemical warfare agents (CWAs) in negative mode. The AEE source was fabricated from an aluminum substrate electrode covered with 1 μm silver nanoparticle-dispersed silicone resin and a thin gold layer. This structure enabled stable tunneling electron emission upon the application of more than 11 V potential under atmospheric pressure. The reactant ion peak (RIP) was observed for the reduced mobility constant (K0) of 2.18 and optimized at the charging voltage of 20 V. This RIP was assigned to O2− by using a mass spectrometer. Hydrogen cyanide was detected as a peak (K0 = 2.47) that was discriminatively separated from the RIP (resolution = 1.4), with a limit of detection (LOD) of 0.057 mg/m3, and assigned to CN− and OCN−. Phosgene was detected as a peak (K0 = 2.36; resolution = 1.2; and LOD = 0.6 mg/m3), which was assigned to Cl−. Lewisite 1 was detected as two peaks (K0 = 1.68 and 1.34; LOD = 12 and 15 mg/m3). The K0 = 1.68 peak was ascribed to a mixture of adducts of molecules or the product of hydrolysis with oxygen or chloride. Cyanogen chloride, chlorine, and sulfur mustard were also well detected. The detection performance with the AEE source was compared with those under corona discharge and 63Ni ionizations. The advantage of the AEE source is the simple RIP pattern (only O2−), and the characteristic marker ions contribute to the discriminative CWAs detection. ne of the missions of analytical chemistry is field detection of hazardous materials. Chemical warfare agents (CWAs) are important analytical targets because they are effective weapons of mass destruction for terrorists1 that display fast action, strong toxicity, and an easily diffusible vapor property.2 Research and development of field CWA detection is technologically and scientifically challenging because CWAs include diverse chemicals ranging from gaseous choking and blood agents, vapor G-type nerve agents, and blister agents to nonvolatile V-type nerve agents, vomiting agents, and lachrymators, and are easily decomposed. They were used in World Wars I and II, and during the Cold War, and are still being produced, stockpiled,2 and used in times of conflict.3 In 1992, a treaty prohibiting the development, production, stockpiling, and use of chemical weapons and calling for their destruction was ratified that came into force in 1997.4 The Japanese cult group AUM Shinrikyo poisoned many by dispersing sarin (GB) in Matsumoto (1994) and the Tokyo

subways (1995).5 In 2013, GB was used during the civil war in Syria,6 and CWAs were used again in 2017.7 Field-deployable CWA detection equipment is useful for personal protection of first responders and for early warning in chemical terrorism.8 Several types of on-site equipment with varied sensitivities, accuracies, and detection performances have been used by military forces, police mobile teams, coast guards, and fire defense teams.1 Regarding on-site identification, mass spectrometry technology has been developed, such as direct analysis in real time9 and gas chromatograph coupled with electron ionization toroidal ion trap MS instrument and solid-phase microextraction sampling.10 National Research Institute of Police Science (NRIPS) has evaluated the commercially available on-site detection equip-

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© XXXX American Chemical Society

Received: February 5, 2019 Accepted: March 21, 2019

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DOI: 10.1021/acs.analchem.9b00672 Anal. Chem. XXXX, XXX, XXX−XXX

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Analytical Chemistry

Figure 1. Schematic diagram of the ion mobility spectrometry instrument.

ment8,11−15 such as gas detection tubes,16 ion mobility spectrometry (IMS) instruments,17−21 arrayed surface acoustic wave sensors,22 and Raman spectrometers.23 In addition, collaborating with other research organizations, NRIPS developed new detection technologies such as the amperometric sensor,24 atmospheric pressure counter-flow chemical ionization ion trap MS,25,26 electron cyclotron resonance ion source MS,27 and low temperature plasma ionization MS.28 Among field-deployable detection equipment, IMS detectors have been extensively utilized for detection of dangerous materials such as CWAs,29 explosives,30 and illicit drugs31 because of their lightweight and portability, ease of operation, and realtime detection.32 IMS can be the so-called first choice field screening device.33 Several detectors have been commercially available over the past two decades.34 IMS instruments differ with respect to the ion separation mode, drift temperature and gas control, dopant usage, and ionization mode. As for the ion separation mode, the straight drift tube instrument with reverse airflow is the most popular. Ions move from the shutter to the collector in the direction of drift voltage.35 The aspiration type detector36 is also available, where ions traverse through an airflow, change direction as a result of a perpendicular drift voltage, and reach several sensor cells. High-field asymmetric waveform IMS and differential mobility spectrometry are the other developed technologies.37 Drift tube temperature, drift gas species,38 and the moisture level39 are essential parameters influencing the ion mobility behavior of the reactant ion peak (RIP) and the target ions. In the ionization and drift regions, many ion/molecule reactions occur that lead to the characteristic ion mobility spectra.40 With regard to dopant usage,41 various solvents (e.g., ammonia, acetone) have been used. By introducing dopant molecules into the ion source and the drift region, the production of RIPs is facilitated or the production of interfering ions is suppressed, or the target ions are welldiscriminated from the interfering ions. The most important IMS parameter is the ionization mode. For atmospheric pressure ionization, a radioactive source33 such as 63Ni (maximum electron energy = 67 keV; average energy = 17 keV), 241Am (α particle, 5.4 MeV), or 3H (maximum electron

energy = 18.6 keV; average energy = 5.7 keV)42 is used. CWAs with high proton affinities offer favorable detection.35 Instead, as nonradioactive source instruments that are free from the regulations of radioisotope usage, corona discharge source43 has been developed and used frequently. The continuous flow mode causes ozone (O 3 ) and nitric dioxide (NO 2 ) accumulation in the ionization region, leading to the disappearance of O2−.44 In order to suppress the undesirable effects of O3 and NO2, the reverse flow mode45 and the pulsed mode46 have been developed. The other ionization sources33 such as glow discharge source47 have been developed, but these have not been used for field CWA detection. The detection performances of the field portable IMS instruments evaluated by NRIPS are shown in the Supporting Information. The low detection sensitivity and the false detectability of blood and choking agents are the typical drawback of IMS instruments. The target ions are all detected as negative ions, which migrate very close to the negative RIP. As another ionization source, electron emitters have long been applied to various vacuum instruments such as electron microscopes, vacuum tubes, cathode ray tubes, and field emission displays. Spindt device (thin-film field emission cathodes with molybdenum cones),48 carbon-nanotube-based electron field emitter,49 surface conduction electron emission display,50 and ballistic electron surface emission by using nanocrystalline polysilicon layers51 have been developed. Typically, these operate in vacuum and are ruptured by sputtered electrons or produced ions accelerated under a strong electric field at atmospheric pressure. Ballistic electron surface emission occurs through the device structure of metal− insulator-semiconductor (MIS), where tunneling electrons are efficiently transferred to the surface with a rather low voltage charging and the resulting hot electrons are emitted. Yokoo et al. realized electron emission at atmospheric pressure by using a silicon-gate metal-oxide-semiconductor cathode.52 Then, MIS-type electron emission was improved to operate well at atmospheric pressure,53 but the lifetimes were too short to allow stable operation, owing to the rapid destruction or deterioration of the emitters. Sharp corporation (Yamatokouriyama, Nara, Japan) recently succeeded in developing a novel B


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and fifth electrodes and exhibited the transmittance of 90%. The two electrode plates were 1 mm apart, and the gate pulse amplitude for the first mesh was controlled by charging at −3.0 and −1.9 kV. The rise time of the shutter pulse was 2 ms. The Faraday plate-type ion collector used (RIKEN KEIKI Co., Ltd.) was shielded 1 mm behind by using an aperture grid (0.1 mm thick, 25.4 mesh, 9 mm diameter, RIKEN KEIKI Co., Ltd.). The ion current was processed by a current-to-voltage amplifier circuit (4.7 MΩ) and amplified (100 times) by the main amplifier circuit (RIKEN KEIKI Co., Ltd.). The IMS spectra were recorded by using a 5 ms time-resolved A/D circuit (RIKEN KEIKI Co., Ltd.). Three high-voltage power supplies were used, one for corona discharge, one for the drift field of IMS (283 V/cm), and one for the gate shutter grid. The shutter grid was controlled by a fast high-voltage transistor switch and triggered by a transistor-transistor-logic generator (RIKEN KEIKI Co., Ltd.). The IMS instrument was operated at ambient temperature (23 °C). The pressure was recorded by a highly sensitive gauge. The drift gas of ambient air purified by passing through 13× molecular sieve (activated at 300 °C, Union Showa K.K., Minato, Tokyo, Japan) cartridge [28 mm (L) × 19 mm (φ)] was drawn at the flow rate of 500 mL/min from the gas inlet at the end of the drift tube, flowed through the drift region against the ion flow, and exhausted to the gas outlet at the top of the IMS instrument. The sample gas was drawn from the inlet at the opposite side of the ionization source at a flow rate of 50 mL/min. Figure 2 shows a schematic diagram of the measurement system of AEE. The AEE device was manufactured by SHARP

electron emission device consisting of a heterogeneous semiconductor layer composed of insulating materials and conductive nanoparticles that displayed stable operation at atmospheric pressure.54 A feature of this device is that the energy of the emitted electrons is as small as several electron volts and can be controlled over long durations.55 The emitted electron manifests as a soft attachment to electron-drawing molecules such as O2 without the formation of harmful byproducts such as O3. This is different from the conventional IMS ionization sources. Therefore, we investigated on the applicability of this atmospheric electron emission (AEE) device as an ionization source of IMS instrument. In this study, we examined the features of the RIPs under AEE ionization. Then, we investigated the detection performance against gaseous and blister CWAs (shown in Figure S1). These agents are recognized in the negative ion mode. A single RIP pattern was observed, and discriminative and sensitive detections of gaseous and blister CWAs were achieved. The ions were assigned by using a mass spectrometer combined with an IMS instrument, because IMS-MS provides definitive molecular assignment.56 We also compared the detection performance under AEE ionization with those obtained under corona discharge and 63Ni ionizations.

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EXPERIMENTAL SECTION Materials. Sulfur mustard (HD, bis(2-chloroethyl) sulfide) and Lewisite 1 (L1, 2-chlorovinyldichloroarsine) were synthesized in the laboratory of NRIPS [>98% purity by gas chromatography-mass spectrometry (GC/MS)].21 Silver nanoparticles (about 5 μm diameter) were purchased from Nihon Superior Co., Ltd. (Suita, Osaka, Japan). Silicone resin was purchased from Shin-Etsu Chemical Co., Ltd. (Chiyoda, Tokyo, Japan). The gold used for plating was purchased from Sanyu Electron Co., Ltd. (Shinjuku, Tokyo, Japan). The other reagents including solvents were commercially obtained as reagent grades. Apparatus. The IMS instrument used in this study was constructed in the laboratory of RIKEN KEIKI Co., Ltd. (Itabashi, Tokyo, Japan). The size of the IMS instrument was 120 mm (length, L) × 50 mm (width, W) × 30 mm (height, H). A schematic diagram of the spectrometer is shown in Figure 1. The instrument was a parallelepiped consisting of an ionization region [19 mm (L) × 27 mm (W) × 15 mm (H)] and a drift region [70 mm (L) × 27 mm (W) × 27 mm (H)]. The instrument consisted of nickel−gold-plated stainless steel thin plate electrodes [27 mm (L) × 27 mm (W) × 0.1 mm (thickness] with 15 mm diameter holes (RIKEN KEIKI Co., Ltd.) that were mounted on a FR-4 circuit board (RIKEN KEIKI Co., Ltd.). The electrodes were located 5 mm apart and connected by a series of resistors to form an electric field. The ionization region was equipped with one ionization source, AEE source, or corona discharge source that is switchable. The AEE source consisted of a substrate electrode and a collector electrode, which were charged at −3.00 kV and −2.98 kV (voltage = 20 V), respectively. The detailed structure is shown below. The corona discharge device consisted of two tungsten needles [1 mm diameter, 40 mm length, 28°, Morita Co., Ltd. (Monma, Osaka, Japan)], and the distance between the two needle tips was 1.7 mm. The corona electrodes were charged at −4.9 and −2.8 kV (corona discharge voltage = 2.1 kV; corona current = a few microamperes). The distance between the ionization source and the shatter grid was 1.5 cm, while the drift length was 7 cm. A single mesh was located at the fourth

Figure 2. Schematic diagram of the atmospheric electron emission device.

Co. (Yamatokoriyama, Nara, Japan), according to a previous paper.54 Silver nanoparticles (about 5 nm diameter) dispersed in toluene (1.3%, w/v) were mixed with silicone resin (100% v/v), layered on an aluminum substrate electrode [10 mm (L) × 6 mm (W) × 0.5 mm (thickness)] and dried to fabricate a 1 μm semiconductive layer (1% silver nanoparticle/polymer composite). Then, gold was sputtered on the surface of the prepared semiconductive layer to 20−40 nm thickness (surface electrode). The effective emission area was fabricated to 5 mm2. The collector electrode for measuring the electron emission was composed of aluminum [40 mm (L) × 15 mm (W) × 1.5 mm (thickness)], and the air gap between the collector electrode and the surface electrode was set at 1 mm. During the electron emission measurement, the air gap was charged at 600 V. Preparation of CWA Vapors. CWA vapors examined were prepared according to the previous papers.21,14 The details are shown in the Supporting Information. IMS Analysis. The sample vapors prepared as described above were introduced into the IMS instrument (RIKEN C


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of HD and L1 were approved by the Ministry of Economy, Trade, and Industry of Japan.

KEIKI Co., Ltd.) by connecting the opening of the gas container to the inlet of the IMS instrument, which was operated in the AEE or corona discharge ionization mode, and the ion mobility spectra were recorded in an external personal computer. The relative humidity at this time was set to 0.78%. The actual ion mobility (K, cm2/V s) could be calculated by using the following equation: K = L2/Vt, where L, V, and t are the drift length (cm), drift voltage (V), and actual mobility drift time (t, ms), respectively. Reduced mobility constants (K0) were used for ion peak identification instead of the drift times, since these were not dependent on the equipment size or operating conditions.33 The K0 (cm2/V s) were calculated from the following equation: K0 = K × 273/T × P/760, where T and P are the temperature (°C) and atmospheric pressure (mmHg), respectively. The IMS instrument was operated at ambient temperature (23 °C). Another IMS instrument (MMTD-D1-C) commercially obtained from Smiths Detection (Watford, United Kingdom) was used. The MMTD instrument [21.6 cm (width) × 20.3 cm (height) × 48.3 cm (long), 5 kg weight] contained a 10 cm drift tube that was maintained at 100 °C and counter-flowed (300 mL/min) with dehumidified air produced by passing through a sieve pack and the ionization source of 63Ni 15 mCi foil. The sample vapor prepared as described above was introduced into the MMTD-D1-C by connecting the opening of the gas container to the inlet of the IMS instrument. Both positive and negative ion mobility spectra were recorded, and the K0 value was obtained automatically by using the mobility of the internal standard compound (calibrant). Mass Spectrometry Analysis. The IMS instrument (RIKEN KEIKI Co., Ltd.) was interfaced with a H-TOF time-of-flight mass spectrometer (TOFWERK, Thun, Switzerland). First, the end wall behind the ion collector was relieved of the main body of the IMS instrument described above, and the remaining part was connected to the sample gas introduction port of the mass spectrometer. The distance between the ion collector and the nozzle (entrance slit) was 22 mm and the width of the nozzle was 0.3 mm. The ion optics between the IMS instrument and the mass spectrometer consisted of an entrance plate, the first quadrupole, the first skimmer, the second quadrupole, the second skimmer, a series of ion lenses, and a slit. The drift gas was flowed at the rate of 1300 mL/min from the gas inlet at the end of the drift tube in the direction opposing the ion flow. The mass spectra (m/z 0− 1000) were collected with a resolution of more than 5000 at the speed of one scan every 0.1 ms. The spectral measurement was performed in the MS mode when the shatter grid of the IMS instrument was fully open or in the IMS mode when both the spectrometers functioned synchronically. Because of poor separation, the MS mode was used for the analysis of gaseous agents, whereas the IMS mode was employed for the analysis of blister agents. The additional explanation can be seen in the Supporting Information. Instrumental Analysis. Scanning transmission electron microscopy (STEM) images were obtained by using Strata DB-STEM 237S (Field Electron and Ion Company, Hillsboro, OR, USA). The emission currents were measured by using Ultrahigh Resistance/Current Meter 5450 (ADC Corporation, Higashimatsuyama, Saitama, Japan). Safety Considerations. HD and L1 are highly toxic. Therefore, protective clothing was worn and these CWAs were carefully handled within a fume hood and destroyed with sodium hypochlorite after the analysis. The synthesis and use

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RESULTS AND DISCUSSION Optimization of AEE. In an AEE system, a strong electric field is formed on the thin insulator film, and hot electrons are produced by a tunneling effect; thus, strong electrical charging is not required for the device.53,54 Therefore, it is possible to avoid the destruction of the device during the AEE through sputtering by eliminating the electron avalanche. Figure S2 shows the STEM image of the AEE device with ∼1 μm thickness of the silver nanoparticle/polymer composite formed on an aluminum substrate as a semiconductive layer. A feature of the device is that the semiconductive layer was formed by nonuniformly dispersing the conductive nanoparticles in an insulating resin. This structure enabled stable electron emission from the device under atmospheric pressure. Figure 3 shows the voltage−current characteristics. When a voltage

Figure 3. Effect of applied voltage on internal device current and emission current in atmosphere (pressure = 1 atm; temperature = 22 °C; humidity = 0.78% RH) of the atmospheric electron emission source.

(Vd) is applied between the surface electrode and the substrate electrode, a fraction of the electrons passing through the semiconductive layer can be emitted from the surface electrode. The electron emission current (Ie) can be measured by applying a positive bias voltage (Ve) to the collector electrode, which is placed opposite the surface electrode. The electrons released into the atmosphere can generate negative ions that move to the collector electrode in the direction of the electric field. The Ie was measured under atmospheric pressure by applying a Ve of 600 V to the collector electrode located at a distance of 1 mm from the surface electrode. The relative humidity at this time was set to 0.78%, similar to the measurement environment of IMS. The internal device current (Id) showed a negative resistance characteristic with increasing Vd. However, Ie monotonically increased. When Vd reached 18 V, the Ie was 40 nA. Therefore, this AEE characteristic could be applied to IMS. The stability and performance at high temperature of the AEE device is described in the Supporting Information. Ion Mobility Spectra of Background Air. Many papers report on RIPs in the negative ion mode (see the Supporting Information). When the background air was drawn to the IMS instrument (RIKEN KEIKI Co., Ltd.) with an AEE source, a single RIP appeared around 10.5 ms. As shown in Figure S3, D


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Figure 4. Ion mobility spectra of blank air under (A) the atmospheric electron emission, (B) the corona discharge, and (C) 63Ni ionizations. For the atmospheric electron emission (the charging voltage = 20 V) and the corona discharge ionizations, the drift length and voltage of the Riken Keiki instrument were 7 cm and 1981 V, respectively. Under the 63Ni ionization, MMTD-D1-C instrument was used. Black arrows and gray arrows show the reactant ion peaks and calibrant ion peak, respectively. The K0 values for the reactant ion peaks are shown.

Figure 5. Mass spectrum of reactant ion peak of background air under the atmospheric electron emission ionization. The charging voltage was set at 20 V.

spectrometry experiment. As shown in Figure 5, from the background air, the main ion at m/z 32 and very minor ions at m/z 60 and m/z 62 were observed. The m/z 32 ion (precise mass = 31.990) was assigned to be O2− with a K0 of 2.18. The m/z 60 and m/z 62 ions could be speculated to be CO3− or N2O2−, and NO3−. The kinetic energy of the emitted electron for attachment to O2 to produce O2− is reported to be less than 1 eV,58 and therefore, this AEE source should effectively produce O2−. The peak kinetic energy of the dissociative electron attachment to O2 is reported to be 6.559 or 8 eV,60 and therefore, with this AEE source, there is little chance of dissociative electron attachment to O2 to produce O− and oxygen radical (O•), which can lead to the formation of O3 and NO2. A simple and sharp RIP pattern may be beneficial for the discriminative detection of the target CWA peaks.

increasing the applied voltage gradually increased the intensity of the RIP. For a high voltage above 20 V, there was the fear of electrode breakdown. Therefore, the applied voltage was set to 20 V. Figure 4A shows the typical ion mobility spectrum of the background air. The RIP that appeared was almost symmetric, with slight tailing. From 8 interday trials, the average of the drift time was 10.49 ms (K0 2.18), and the standard errors (SE) of the drift time and peak intensity were 0.095 ms and 15.9%, respectively. As for the sharpness of the peak, the theoretical plate number (N57) was 1660 (SE = 30.4%). The signal-to-noise ratio of the RIP was 654 (average). Under AEE, low-energy electrons (with a peak around 5 eV) could be produced,54,55 which could be detected in this experiment (Figure 3). A single RIP was observed, suggesting the formation of only O2−. This was confirmed from the mass E


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Figure 6. (A) Ion mobility spectrum (9 mg/m3) and (B) mass spectrum (450 mg/m3) of hydrogen cyanide under atmospheric electron emission ionization. The charging voltage was set at 20 V. The closed arrows show the target peaks, whereas the open arrows indicate the reactant ion peaks. The mass spectrum was measured in the MS mode. (A) The chemical structure and the K0 value of hydrogen cyanide-derived peak are shown.

contaminated chlorinated compounds present in the background air. With corona discharge, not only ions but also O3 and NO2 are produced, and the transition of the RIPs can be recognized.44,69 The radioactive source (63Ni) emits electrons and produces O2−, but the kinetic energy is so high (average = 17 keV, maximum = 67 keV)42 that dissociative electron attachment to O2 produces O− and O•. Then, O− reacts with CO2 and O2 to produce CO3− and O3−, respectively. O• reacts with N2 and O2 to produce NO and O3, respectively. NO is oxidized to form NO2. O3− reacts with CO2 to produce CO3−. O3 and NO2 cause RIP transition, ultimately producing NO3−, as seen in the corona discharge. Eventually, CO3− and O2− are preferably formed under radioactive ionization. In contrast, the RIP observed under AEE ionization showed a simple pattern with a single O2− peak. It is expected that the detection of gaseous CWAs is advantageous by using AEE ionization because the ions derived from the gaseous CWA-derived peaks should migrate around the front of the RIP (O2−) position. On the other hand, for the other ionizations, the target CWAderived peaks merged with the RIPs because the RIPs were widely dispersed. Ion Mobility Spectra of Blood Agents. Blood agents are detected as OCN− H2O (K0 = 2.50) for AC and OCN− H2O (K0 = 2.50) and Cl− (K0 = 2.73) by using a portable detector (RAID I) with 63Ni source for about 100 °C drift temperature operation.70 We previously reported that the IMS instrument (SABRE 4000) with 63Ni source and 106 °C drift temperature operation provided the same ion peak (K0 = 2.46) for both AC and CK,19 and the IMS instrument (LCD 3.3) with corona discharge source and ambient temperature drift operation provided peaks corresponding to K0 = 2.19−2.33 for AC and peaks corresponding to K0 = 2.06−2.28 for CK.21 The AC-

We experimentally compared the RIP under AEE ionization with those obtained for the other ionizations. As shown in Figure 4B, under continuous flow corona discharge ionization, the main peak appeared at 10.64 ms (K0 = 2.14), with the middle peak at 9.03 ms (K0 = 2.52), and a minor peak at 9.81 ms (K0 = 2.32). Under 63Ni ionization (Figure 4C), the major peak appeared at 8.70 ms (K0 = 2.20), with minor peaks at 8.23 ms (K0 = 2.32), 7.68 ms (K0 = 2.49), and 7.08 ms (K0 = 2.70). As shown in Figure S4, under continuous flow corona discharge ionization, the background air provided the mass spectrum, where the main ion appeared at m/z 62 (precise mass = 61.988), with minor ions at m/z 46 (precise mass = 45.993) and m/z 125. From the information provided in the reference paper concerning the generation of ions under continuous flow corona discharge,44 the ions at m/z 62, m/z 46, and m/z 125 could be assumed to be NO3−, NO2−, and NO3− HNO3. The K0 values may be changeable, depending on the drift temperature,61 and the literature values may have fluctuated because of inaccurate measurement. A strict comparison is necessary to obtain the correct K0 values among the various IMS instruments,62 and standard compounds are required to adjust the K0 values.63 However, by considering the molecular formula obtained by MS analysis and the K0 values reported under corona discharge ionization (2.29 for NO3−; 2.02 for NO3− HNO3),64 the RIPs (K0 = 2.52; K0 = 2.32; K0 = 2.14, Figure 4B) could be assumed to be those of NO2−, NO3−, and NO3− HNO3. As for the RIPs observed under 63Ni ionization, they could be ascribed to a mixture of O2− (H2O)n, CO3−, NO2−, or CO4− (H2O)n,65−68 although molecular assignment by MS could not be performed. The small fast migrating RIP (K0 = 2.70, Figure 4C) was superimposed with the chloride ion (Cl−) peak (described later), therefore, the ion may be derived from the Cl− of the F


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Table 1. Detection Performances of Chemical Warfare Agents in Ion Mobility Spectrometry with Atmospheric Electron Emission Ionization agent

drift time (ms)

K0b

Nc

resolution against RIP

standard error (%) of peak heightd

LODe (mg/m3)

a

10.48 9.24 9.90 9.25 9.64 9.78 14.39 9.68 13.56 17.07 9.78

2.18 2.47 2.30 2.46 2.36 2.33 1.58 2.35 1.68 1.34 2.33

1600 2400 6500 8200 4200 3700 5700 6200 780 890 4900

1.4 0.70 1.6 1.2 0.94 3.8 0.79 1.6 2.9 0.66

3.1−26.1 (11.6) 0.6−14.3 (6.6) 1.1−16.3 (7.0) 2.4 = 10.1 (6.2) 9.1−50.9 (25.3) 30.1−53.9 (42.6) 79.9−99.0 (86.7) 71.5−96.6 (81.9) 72.8−90.1 (81.4) 48.7−89.2 (75.6)

0.057 7.0 (560f, 7.8g) 15 (220f, 12g) 1.7 0.6 2.3 13 (540)f 12 15 8.7 (57)f

air (RIP ) hydrogen cyanide cyanogen chloride phosgene chlorine sulfur mustard Lewisite 1

a

Reactant ion peak. bReduced ion mobility. cTheoretical plate number of the peak. dThe lowest and highest values obtained within the measured points on the calibration plots (Figure S5, S7, S12, S14, S17, and S19) are presented, with the average values included inside the parentheses. e Limit of detection calculated by using the signal obtained as the value of the slope of the fitted equation at zero concentration and the noise obtained as the standard deviation (σ) of the baseline signals. fCalculated for the situation where the target CL peak appears as the leading peak to the RIP and the RIP signal at the CK peak position is used as noise. gObtained as the slope of the fitted equation of the second derivative plot (Figure S9) at zero concentration, with the RIP value at the CK peak position used as noise.

amount of produced ions did not exceed 0.1 V, whereas, the AC calibration plot saturated above 0.1 V. The N values, resolutions against the RIP, theoretical LOD values, and practical LOD values (calculated by using the background air signals at the CK peak positions as noise), and the RSD range along with the average, are shown in Table 1. Because the target CK-derived peaks were not resolved from the RIP, it seemed difficult to determine CK with a low concentration. Previously, we reported that the commercial IMS instrument (SABRE 4000) utilized the second derivative of the IMS signal for advanced recognition of targets.19 As shown in Figure S8, the second derivative plot revealed clearer peaks at 9.90 ms (K0 = 2.30) and 9.23 ms (K0 = 2.46). The calibration plots of the second derivative of the ion intensities against the concentrations (Figure S9) were concave for both peaks (K0 = 2.30; K0 = 2.46). The practical LOD values (calculated by using the background air signals at the CK peak positions as noise) were almost equal to the theoretical LOD values (Table 1). The mass spectrum of the CK vapor (11000 mg/m3) is shown in Figure S6B, which represents a complicated mass spectrum. Besides O2− at m/z 32, the ion at m/z 42 (precise mass = 42.057) was assigned as OCN− (main ion), the ion at m/z 26 (precise mass = 26.003) was assigned as CN−, the ion at m/z 35 (37) as Cl−, the ion at m/z 46 (precise mass = 45.993) as NO2−, the ion at m/z 60 (precise mass = 60.008) as OCN− H2O, and the ion at m/z 62 was presumed to be CN− (H2O)2, which were the minor ions observed. The ion at m/z 46 could be ascribed to the artifact due to the high CK concentration, which led to the production of oxidative byproducts. Comparison of AEE ionization with the other ionizations is important to ascertain the advantage of AEE ionization. The details are shown in Figures S10 and S11. Because the ACderived peaks merged with the superimposing RIPs, discriminative detection of AC was not achieved under corona discharge and 63Ni ionizations, which suggested that the sensitivity for practical detection was impaired. Also, because the target peaks merged with the superimposing RIPs, discriminative detection of CK was disadvantageous, which indicated the low sensitivity for practical detection (Tables S1 and S2). AEE ionization provided efficient detection of AC with lower LOD value (0.057 mg/m3), based on the

derived and CK-derived peaks could not be well-separated from the RIPs. As shown in Figure 6A, for the AC vapor (9 mg/m3) under AEE ionization, the AC-derived peak at 9.24 ms (K0 = 2.47) was well-separated from the RIP corresponding to K0 = 2.18. The peak was sharp with an N value of 2400. The resolution57 against the RIP was 1.4, indicating good base peak separation. As shown in Figure S5, the calibration plot of the peak heights against the concentration exhibited a concave pattern, where, in the low concentration range, the plot was linear, which then saturated and declined. From the value of the slope of the linear portion, the limit of detection (LOD) was calculated by using the baseline noise, yielding the value of 0.057 mg/m3. With regard to repeatability, the RSDs for the respective measurement points on the calibration plot ranged from 3.1% to 26.2% (average 11.6%) (Table 1). The mass spectrum of the AC vapor is shown in Figure 6B. It was measured in the MS mode, because the IMS separation of AC and the RIP could not be achieved. A high concentration of the vapor was necessary to obtain the mass spectral ions. From the AC vapor (450 mg/m3), besides the main ion of O2− at m/z 32, the ion at m/z 42 (precise mass = 42.057) was assigned as OCN− (major ion); the ion at m/z 26 (precise mass = 26.003) was assigned as CN−, the ion at m/z 46 (precise mass = 45.993) as NO2−, and the ion at m/z 60 (precise mass = 60.008) as OCN− H2O, which were the minor ions observed. The ion at m/z 46 could be ascribed to the artifact due to the high AC concentration, which led to the production of oxidative byproduct ions. OCN−can be formed by the oxidation reaction of HCN with O2−. Because the ion mobility spectrum of AC shows only two peaks, one RIP (O2−) and one AC-derived peak (K0 = 2.47), the latter should be ascribed to a mixture of m/z 26 CN−, m/z 42 OCN−, and m/z 60 OCN− H2O. For the CK vapor (23 mg/m3), the main peak at 9.90 ms (K0 = 2.30) and a minor peak at 9.25 ms (K0 = 2.46) were observed as leading peaks to the RIP (Figure S6A). As shown in Figure S7, the calibration plots of the ion peak heights against the concentrations were linear up to a high concentration for both peaks (K0 = 2.30; K0 = 2.46). The reason that the calibration plot for the K0 = 2.30 ion did not saturate in the high-concentration range may be that the G


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Figure 7. (A) Ion mobility spectrum (442 mg/m3) and (B) mass spectrum (486 mg/m3) of phosgene under atmospheric electron emission ionization. The charging voltage was set at 20 V. The closed arrows show the target peaks, whereas the open arrows indicate the reactant ion peaks. The mass spectrum was measured in the MS mode. (A) The chemical structure and the K0 value of phosgene-derived peak are shown.

discriminative peaks derived from OCN− and CN−, and is advantageous over the other ionizations, in which the target peaks are often confused with the RIPs, resulting in moderate practical LOD values (Tables S1 and S2). Furthermore, detection of CK is possible in the form of characteristic tailing peaks to the RIP, which was derived from OCN−, CN−, and OCN− H2O. The first two ions are specific to AC and are thought to be produced through decomposition of the CK molecule. The LOD value for CK under AEE ionization (7.8 mg/m3) was compatible with that under 63Ni ionization and superior to that under corona discharge ionization. Ion Mobility Spectra of Choking Agents. Choking agents are difficult to determine both in laboratories and in the field.8 As for IMS, it is reported that under 63Ni ionization and room temperature drift operation, choking agents reveal Cl− (H2O)n (K0 = 2.32) and Cl− O2, Cl− CO2 (K0 = 2.16) for CG and Cl2− (H2O)n (K0 = 2.19) and Cl2− O2, Cl2− CO2 (K0 = 1.93) for CL, which appear just before the RIP position.71,72 Phosgene is detected as Cl− (K0 = 2.77) and Cl− (H2O)2 (K0 = 2.42) by a portable IMS instrument (RAID I) under 63Ni ionization and about 100 °C drift temperature operation.70 We also reported that the IMS instrument (SABRE 4000) under 63 Ni ionization and 106 °C drift temperature operation revealed a peak (K0 = 2.66) for CG and chloropicrin and a peak (K0 = 2.29) for CL,19 and the portable IMS instrument (LCD 3.3) under corona discharge ionization and ambient temperature drift operation displayed peaks (K0 = 2.14−2.29) for CG and peaks (K0 = 2.13−2.19) for CL.21 Under 63Ni ionization, CG can be detected in the form of the final breakdown product Cl− and its hydrated adduct and CL as Cl2− and its hydrated adduct. As shown in Figure 7A, for CG vapor (442 mg/m3) under AEE ionization, a peak at 9.64 ms (K0 = 2.36) well-separated

from the RIP was observed. As displayed in Figure S12, the calibration plot of the ion peak height against the concentration was concave. The N value, resolutions against the RIP, LOD value, and RSD range with the average are shown in Table 1. Because the CG-derived peak was wellisolated from the RIP, it was easy to detect CG at low concentrations. The mass spectrum (Figure 7B) of the CG vapor (486 mg/m3) indicates that besides the ion at m/z 32 (O2−), the ion at m/z 35(37) assigned as Cl− (main ion) and the ion at m/z 70(72) assigned as Cl2− (minor peaks) are observed. Therefore, the two peaks observed in the ion mobility spectrum might be a RIP (O2−) and a CG-derived ion peak (K0 = 2.36), which could be ascribed to the hydrated chloride ion [Cl− (H2O)n] that probably produced Cl− through adiabatic expansion at the interface between the IMS and TOF/MS instruments through dehydrogenation. For the CL vapor (159 mg/m3), a peak at 9.78 ms (K0 = 2.33) was observed as the leading peak to the RIP (Figure S13A). As shown in Figure S14, the calibration plot of the ion peak height against the concentration is concave and saturates at around 100 mg/m3. The detection performances are shown in Table 1. Although the target peak partially overlapped with the RIP (K0 = 2.36), it could be well-determined. The mass spectrum (Figure S13B) of the CL vapor (317 mg/m3) indicates that besides the ion at m/z 32 (O2−), the ion at m/z 35(37) assigned as Cl−(major ion), the ion at m/z 70(72) assigned as Cl2− (minor ion), and the ion at m/z 62, presumed to be NO3− as a very minor ion, are observed. Therefore, the two IMS peaks could be O2− and CL-derived ion peak (K0 = 2.33), which is ascribed to a mixture of hydrated chlorine (Cl2−·(H2O)n) and hydrated chloride ions (Cl− (H2O)n); these ions probably provided Cl2− and Cl−, which were H


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Figure 8. (A) Ion mobility spectrum (50 mg/m3) and (B) mass spectrum (3800 mg/m3) of Lewisite 1 under atmospheric electron emission ionization. The charging voltage was set at 20 V. The closed arrows show the target peaks, whereas the open arrows indicate the reactant ion peaks. The mass spectrum was measured in the IMS mode in the slow migration region. (A) The chemical structure and the K0 values of the Lewisite 1derived peaks are shown.

adduct ([M + O2]−), a peak (K0 = 2.71) of Cl−, and a peak (K0 = 2.37) of Cl− (H2O)2, whereas L1 is detected in the forms of a peak (K0 = 1.62) of a decomposition product (AsCl2C2H2−) and a peak (K0 = 1.31) of a superoxide molecular adduct ([M + O2]−). Under 63Ni ionization and ambient temperature drift operation, L1 is detected in the forms of a peak (K0 = 1.66) of the chloride molecular adduct (m/z 241−247) and a peak (K0 = 1.70−1.72) of the adduct of L1 hydrolysis product (m/z 223, 225, and 227).65 We also reported that the IMS instrument (SABRE 4000) with 63Ni source and 106 °C drift temperature operation provided a peak (K0 = 2.66) for HD and a peak (K0 = 1.56) for L1,19 and the portable IMS instrument (LCD 3.3) with corona discharge source and ambient temperature drift operation provided a peak (K0 = 1.47) for HD and a main peak (K0 = 1.58) and a minor peak (K0 = 1.73) for L1.21 As shown in Figure 8A, for the L1 vapor (50 mg/m3) under AEE ionization, L1-derived peaks are observed at 13.56 ms (K0 = 1.68) and 17.07 ms (K0 = 1.34), which are broad peaks, and at 9.78 ms (K0 = 2.33), which is a leading peak to the RIP. As shown in Figure S17, the calibration plots of the peak heights against the concentrations for the K0 = 1.68 ion and K0 = 1.34 peaks were parabolic. The plot for the K0 = 2.33 peak exhibits a scattered pattern. The N values, resolutions against the RIP, theoretical LOD values, and practical LOD values (calculated by using the background air signals at the L1 peak positions as noise), and the RSD ranges along with the averages, are shown in Table 1. Because the L1-derived peaks with slow migration are well-isolated, it is easy to detect L1, although the peak intensity is rather low compared with the other agents. The peak corresponding to K0 = 2.33 could be used to ascertain the existence of L1. The mass spectrum (Figure 8B) of the L1 vapor (3800 mg/m3) indicates that for molecular weights

produced through adiabatic expansion at the interface between the IMS and TOF/MS instruments through dehydrogenation. The results of IMS of choking agents under the other ionizations were performed (Figure S15, S16). Because the CG-derived peak was not perturbed by the RIP, discriminative detection of CG could be achieved under the corona discharge ionization (Table S1). In contrast, because the GC-derived peak merged with the superimposing low RIP, discriminative detection of CG was hampered at low concentrations under the 63Ni ionization, which suggested that the sensitivity for practical detection was impaired (Table S2). As for CL, because the target main peak merged with the superimposing RIP, discriminative detection of CL was disadvantageous under the corona discharge ionization, which suggested the low sensitivity for practical detection (Table S1). Because the target peak merged with the superimposing middle RIP, therefore, discriminative detection of CL was hampered under the 63Ni ionization, which indicated that the sensitivity for practical detection was impaired (Table S2). AEE ionization provided efficient detection of CG, based on a discriminative peak derived from Cl−, and is equivalent to the other ionizations that provide target peaks that are isolated from the RIP. In addition, detection of CL was possible with the characteristic tailing peak to the RIP, which was derived from Cl− and Cl2−. AEE ionization with a reasonably low LOD value is still advantageous over the other ionizations providing target peaks convoluted with the RIPs, resulting in impaired LOD values. Ion Mobility Spectra of Blister Agents. As for IMS with a portable instrument (RAID I) under 63Ni ionization and about 100 °C drift temperature operation,70 HD is detected in the forms of a peak (K0 = 1.56) of a superoxide molecular I


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Analytical Chemistry greater than m/z 150, many chlorinated peaks are observed. The ion at m/z 203(205) is presumed to be [M − Cl + O2]−, the ion at m/z 206(208) is presumed to be a molecular ion, the ion at m/z 220(222) is presumed to be [L1ly + O2]−, the ion at m/z 223(225) is presumed to be [L1ly + Cl]−, the ion at m/ z 238(240,242) is presumed to be [M + O2]−, and the ion at m/z 241(243,245) is presumed to be [M + Cl]−. Because the ion mobility spectrum of L1 (Figure 8A) shows four peaks derived from O2− and L1 (K0 = 1.68; K0 = 1.34; and K0 = 2.33), the broad peak (K0 = 1.68) could correspond to a mixture of ions decomposed from L1-related compounds: [M − Cl + O2]−, [L1ly + O2]−, [L1ly + Cl]−, [M + O2]−, and [M + Cl]−, where “L1ly” is the L1 hydrolysis product. The ion with K0 = 1.34 may be derived from the L1 dimer, the ion intensity of which in mass spectrometry is too low to be observed. The ion with K0 = 2.33 could be ascribed to Cl− (H2O)n. As shown in Figure S18A, for the HD vapor (150 mg/m3) under AEE ionization, HD-derived peaks are observed at 14.39 ms (K0 = 1.58), which is the main peak, and 9.68 ms (K0 = 2.35), which is the leading peak to the RIP. As revealed in Figure S19, the calibration plot of the ion peak heights against the concentration are concave. The detection performances are shown in Table 1. Because the slow migrating HD-derived peak (K0 = 1.58) is well-isolated, it is easy to detect HD. The peak corresponding to K0 = 2.35 could be used to ascertain the existence of HD. The mass spectrum (Figure S18B) of the HD vapor (2400 mg/m3) indicates that for molecular weights greater than m/z 100, minor ions at m/z 143(145), m/z 129(127), and m/z 112 are observed; however, they could not be assigned for determination of the structure. In the region of low molecular weights, the ion at m/z 62 is presumed to be NO3− and the ion at m/z 83(85) is presumed to be Cl− O3. However, the peak of HD corresponding to K0 = 1.58 could be that of a pseudomolecular ion. The results of IMS of blister agents under the other ionizations were performed (Figures S20 and S21). The discrimination of L1-derived peak from the RIP was achieved under the corona discharge ionization, suggesting a moderate detection sensitivity (Table S1), and because discrimination of the L1-derived peaks from the RIP was achieved under the 63 Ni ionization, high detection sensitivity could be realized (Table S2). As for HD, because discrimination of HD from the RIP was achieved, a high detection sensitivity could be obtained (Table S1), and because the target peak merged with the superimposing RIP, discriminative detection of HD was hampered under 63Ni ionization, which suggested that the sensitivity for practical detection was impaired (Table S2). AEE ionization provided efficient detection of HD based on a discriminative peak derived from two molecular or hydrolysate adduct ions and is equivalent to the other ionizations providing distinguishable peaks that can be isolated from the RIP. Similarly, the detection of L1 is efficient with reasonably low LOD value, based on a discriminative peak derived from possibly a pseudomolecular ion, and is equivalent to corona discharge ionization, which provides similar distinguishable peaks that can be isolated from the RIP; it is advantageous over 63 Ni ionization, which provides nonspecific peaks derived from Cl−. Production of Marker Ions Under the AEE Ionization. The IMS charts obtained under AEE ionization of six CWAs are overlaid on one chart (Figure S22). The characteristic marker peaks were noticed, with the respective K0 values being

different from each other and from that of the RIP (Table 1). All the LOD values were less than one hundredth of 1 min lethal dosage (LCt50) × 1 min, indicating that IMS with an AEE source should fulfill the requirement for CWA detection as part of on-site countermeasures against chemical warfare/ terrorism.8 The mechanism of the maker ions from CWAs based on ion/molecule reaction is discussed in the Supporting Information.

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CONCLUSION Compared with corona discharge ionization and 63Ni ionization, AEE ionization was proven to be advantageous for IMS detection of the negative ions produced from CWAs. The RIP produced was exclusively that of O2−, and therefore, discriminative detection of blood agents, choking agents, and blister agents was accomplished owing to the high resolution between the agent-derived peak and the RIP, along with characteristic production of agent-derived ions as a consequence of the reaction of the agents with O2−. This results in sensitive detection of CWAs with low LOD values.

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.analchem.9b00672. Introduction, experimental information, preparation of CWA vapors, mass spectrometry analysis, optimization of AEE, ion mobility spectra of background air, ion mobility spectra of blood agents, ion mobility spectra of choking agents, ion mobility spectra of blister agents, and production of marker ions under AEE ionization (PDF)

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. ORCID

Yasuo Seto: 0000-0002-0983-4162 Present Addresses ∥

Y.S.: RIKEN SPring-8 Center, 1−1−1 Kouto, Sayo-cho, Sayogun, Hyogo 679−5148, Japan. ⊥ R.H. and Y.O.: Tokyo Metropolitan Police Department, 2− 1−1 Kasumigaseki, Chiyoda-ku, Tokyo 100−8929, Japan. @ T.N.: Technopro R&D, 1−15−1 Benten, Chuo-ku, Chiba, Chiba 260−0045, Japan. Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS The part of this work pertaining to the corona discharge IMS instrument and mass spectrometry combined with ion mobility spectrometer was carried out under the R&D Program for implementation of anti-Crime and anti-Terrorism Technologies for a Safe and Secure Society by using the funds for Integrated Promotion of Social System Reform and Research and Development, which were provided by the Ministry of Education, Culture, Sports, Science and Technology, Japan. This work was also supported by a grant-in-aid for scientific research (KAKENHI: 16H03140) from Japan Society for the Promotion of Science (JSPS). J


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