Miniaturized Ion Mobility Spectrometer with a Dual-compression

Jun 18, 2019 - Miniaturized Ion Mobility Spectrometer with a Dual-compression Tristate Ion Shutter for On-site Rapid Screening of Fentanyl Drug Mixtur...
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Cite This: Anal. Chem. 2019, 91, 9138−9146

Miniaturized Ion Mobility Spectrometer with a Dual-Compression Tristate Ion Shutter for On-Site Rapid Screening of Fentanyl Drug Mixtures Hong Chen,†,‡ Chuang Chen,*,† Wei Huang,† Mei Li,†,‡ Yao Xiao,†,‡ Dandan Jiang,† and Haiyang Li*,†

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†

Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, People’s Republic of China ‡ University of Chinese Academy of Sciences, Beijing 100049, People’s Republic of China S Supporting Information *

ABSTRACT: The hidden presence of fentanyl and new psychoactive substances in established illicit drugs has led to a great number of unintentional fatal overdoses, justifying the urgent need for portable tools for the rapid screening of various drugs. Ion mobility spectrometry, as a rapid detection technique, has been widely used in detecting illicit drugs, whereas it is insufficiently sensitive for bigger ions due to the mobility discrimination of an ion shutter. In this work, a miniaturized ion mobility spectrometer with an inner diameter of 14 mm and a drift length of 38.9 mm and equipped with a novel dual-compression tristate ion shutter has been developed, which could greatly reduce the mobility discrimination by compressing the ion packet twice during the injection process. The best gating performance of the dualcompression tristate ion shutter was about three times as high as that of the tristate ion shutter and twice as high as that of the Tyndall-Powell shutter. For example, the peak height was increased by 150 or 40% when the resolving power was the same, whereas the resolution of two neighboring peaks was improved by 46 or 19% when the peak heights were the same. In screening of fentanyl drug mixtures, the new shutter enhanced the identification accuracy of constituents by making peaks of slow dimer ions and complex ions observable. Besides, the new shutter helped to achieve high sensitivity for drug ions spreading a wide ion mobility range from 0.644 to 2.032 cm2 s−1 V−1, demonstrating its potential use in the analysis of other mixtures and the detection of large ions.

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raphy−mass spectrometry (GC/MS) and liquid chromatography−mass spectrometry (LC/MS) are considered to be the gold standard methods for drug analysis, whereas these methods are not suitable for large-scale screening due to the bulky devices and the time-consuming analysis procedure.9,10 Ambient mass spectrometry (AMS) eliminates the chromatographic step and reduces the sample preparation procedure, making it capable of rapidly determining target compounds.11 Nevertheless, for on-site drug testing, AMS-based tools still need improvements in portability. Ion mobility spectrometry (IMS) is a rapid analysis technique suitable for portable instruments12 and has been widely used in detecting illicit drugs.13−15 In IMS, the introduced drug sample is ionized in the ionization region; then, a small packet of the product ions is injected into the

llicitly sourced fentanyls and a growing number of new psychoactive substances (NPSs) are often mixed into drugs that have already been consumed for years, adding significant complexity to the drug problem.1 Polydrug abuse has led to a great number of fatal overdoses because the users are often unaware of the contents or are lacking in knowledge about the substances they are taking.2−4 For example, more than 5000 overdose deaths from fall 2013 to spring 2017 in the United States were related to fentanyl and its analogues.5 At the present, immunoassays are most commonly used for drug screening, featuring fast analysis and low cost; however, only a limited number of illicit drugs can be identified. Furthermore, because of cross-reactivity, immunoassays suffer from high false-positive rate and cannot distinguish between drug analogues.6,7 Raman spectroscopy is a well-established technique with commercial hand-held instruments available for drug analysis. However, the interferential fluorescence of the sample background may lead to false-negative alarms.8 Featuring high specificity and good selectivity, gas chromatog© 2019 American Chemical Society

Received: April 7, 2019 Accepted: June 18, 2019 Published: June 18, 2019 9138

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Figure 1. Schematic structures of the fentanyl, fentanyl analogue, NPSs, and established illicit drugs detected in this work.

Figure 2. (a) Schematic of the ion mobility spectrometer and shutter controlling schemes for (b) dual-compression tristate ion shutter, (c) Tyndall-Powell (TP) ion shutter, and (d) tristate ion shutter. V1, V2, and V3 are the positional potentials of G1, G2, and G3, respectively. All ion shutters are open from t0 to t1 and are closed at other times. The gate opening time (tg) is t1 − t0.

drift region by an ion shutter for ion-mobility-based separation. In the ion shutter closed state, the applied gate closing voltage (GCV) usually produces a depletion region in which all ions will be discharged.16,17 Therefore, ions cannot be effectively

injected if they have not passed through the depletion region after the ion shutter opening interval, leading to the so-called ion mobility discrimination effect and hence poor sensitivity for slower drug ions.18 Increasing the gate opening time can 9139

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drift region (14 mm i.d.), a 15.0 mm long ionization region (14 mm i.d.), and a cylindrical 5 mCi 63Ni ion source (5.5 mm i.d.), schematically shown in Figure 2a. The ion shutter was constructed by three identical 0.05 mm thick stainless-steel wire grids (G1, G2, and G3) separated by two circular Teflon insulators. The wires spanned a hole of 14 mm diameter on a disc of 20 mm diameter. Three ion shutter operation modes were successively used for this work. In the tristate ion shutter, the gaps between the two adjacent grids were both 0.5 mm, similar to the values reported in ref 21. In the TP ion shutter and dual-compression tristate ion shutter, the gap between G1 and G2 remained at 0.5 mm, whereas the gap between G2 and G3 was enlarged to 4 mm to generate a region in which ions could be compressed. A homogeneous electric field of 90.0 V/ mm was formed in the whole drift tube by a high-voltage power supply (HV) with an adjustable output from 0 to +7000 V, a serial of resistors, and a rheostat (R1). The ion current received by the Faraday plate was amplified by a two-stage preamplifier with a gain of 109 V/A and a bandwidth of 41 kHz and then fed to an oscilloscope (Tektronix, 2024C) for recording. The drift tube was kept at ambient temperature. Clean air purified by activated carbon and a fresh molecular sieves trap was used as drift and carrier gases at flow rates of 300 and 200 mL min−1, respectively. The humidity of the gases was kept below 1 ppmv. A thermal desorber26 set to 240 °C was used to introduce the illicit drugs. First, 1 μL of test drug solution was deposited on an aluminum swab; then, the swab was inserted into the thermal desorber after vaporization of the solvent. For the test of drug mixtures, 1 μL of different test drug solutions was successively deposited on an aluminum swab before thermal vaporization. The carrier gas passing through the desorber brought the sample vapor into the IMS apparatus for analysis. Acetone or dimethyl methylphosphonate (DMMP) was introduced into the IMS by purging two permeation vials (1.5 mL, Agilent). The concentration of acetone was adjusted to be high enough (>20 ppmv) to consume all of the reactant ions and form a single peak for convenient investigation. To obtain a stable DMMP concentration in the carrier gas, the DMMP vial was first adjusted to see the three peaks of hydrated proton, DMMP monomer, and DMMP dimer simultaneously and then purged continually for a week before use. DMMP dimer ion with reduced ion mobility (K0) of 1.40 cm2 s−1 V−1 was used to calculate the reduced mobility of other ions. Ion Shutter Operation Modes. For the dual-compression tristate ion shutter (Figure 2b), two individual high-voltage pulses were applied to G2 and G3, respectively. The GCV applied to G2 (GCV2) was generated by an isolated highvoltage power supply (IHV1) floating on the positional potential of G2 (V2) with an adjustable output of 0 to 800 V. The GCV applied to G3 (GCV3) was generated by another isolated high-voltage power supply (IHV2) floating on the positional potential of G3 (V3) with an adjustable output of 0 to 800 V. Because increasing the GCVs would enhance their compression effect,23 GCV2 and GCV3 were both set at 800 V. First, the region between G2 and G3 was closed by setting G2 at V2 and setting G3 at the output potential of IHV2 (>V2). At timing point t0, the shutter was opened by switching the potential of G3 back to V3, so the ions started to move from the left to the right of G2. At timing point t1, the region between G1 and G2 was closed by switching the potential of G2 to the output potential of IHV1 (>V1, the positional

partly cancel out the discrimination for slower ions; however, this will lead to the injection of broader ion packets for fast ions and increase the likelihood of overlap between two neighboring peaks. The peak overlap will be especially acute in the analysis of drug mixtures using portable IMS devices, which are often equipped with short drift tubes of low resolving power. In our previous study, the discrimination effect of the Tyndall-Powell (TP) shutter19 was decreased through shortening the time for the ions to traverse the depletion region with an increased gate penetration voltage in the shutter open state,20 whereas the discrimination effect cannot be completely eliminated in that way. To further decrease the discrimination effect, Kirk et al.21 developed a tristate ion shutter consisting of three parallel grids. In the first state, the ion flow was stopped before the center grid; in the second state, the shutter was opened and ions started to drift from the center grid to the drift region; and in the third state, the ion flow was cut off at the center grid to generate an ion packet. Because the starting line and the cutting off line of an ion packet were both at the center grid, the mobility discrimination effect was significantly reduced. Apart from causing the mobility discrimination effect, GCV also affects the movement of the injected ion packet by changing the electric field distribution profile behind the ion shutter.22,23 Specifically, when a positive GCV is applied to a positive mode IMS, the injected ion packet will be compressed in the temporal domain by the partially strengthened electric field behind the ion shutter, leading to a narrower peak width and thus a higher peak height. Therefore, the compression effect of GCV on the injected ion swarm will enhance the sensitivity and resolving power simultaneously. Speculatively, the compression would be more effective in miniaturized IMS instruments because other factors like diffusion and Coulombic repulsion will play less important roles in the sensitivity and resolving power when the drift times of the ions become shorter.24,25 We had demonstrated that the compression effect can be significantly enhanced by simply raising the GCV, which, however, would enlarge the depletion region and aggravate the mobility discrimination effect.23 To sensitively detect various drugs simultaneously, a miniaturized IMS apparatus was built in this work. It was equipped with a novel dual-compression tristate ion shutter consisting of three parallel grids. The ion shutter used two separate ion-shutter-controlling voltage pulses to realize a fieldswitching sequence that was the same as that of the tristate ion shutter and meanwhile compress the injected ion packet twice. The performance of the new shutter was compared with that of the tristate ion shutter and the TP ion shutter by detecting a variety of drugs and drug mixtures constituted by conventional drugs and fentanyl, fentanyl analogue, or an NPS (Figure 1). For the three shutters, the GCV hardly affected the ionization fields if the shutter controlling pulses were not applied to the grid facing the ionization region. Thus a comparison solely regarding the compression effect of the GCV on the injected ion packet among the three shutters could be conducted. This article details the design and operation of the miniaturized IMS and shows how the new ion shutter surpasses other shutters in both IMS sensitivity and resolving power for the analysis of drug mixtures.

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EXPERIMENTAL SECTION IMS Apparatus. The IMS apparatus was constructed using a stack-design with a drift tube consisting of a 38.9 mm long 9140

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Figure 3. IMS spectra obtained under (a) the dual-compression tristate ion shutter mode, (b) the TP ion shutter mode, and (c) the tristate ion shutter mode when analyzing DMMP of stable concentration at varying tg. P1, P2, and P3 are the reactant ion peak (RIP), the DMMP monomer peak, and the DMMP dimer peak, respectively. The height of RIP is normalized in each spectrum. The reduction of discrimination of slower ions by dual-compression tristate and tristate ion shutters is clearly visible, which is also indicated by (d) the peak area ratio of P3 and P1 (AreaP3/ AreaP1) as a function of tg.

Figure 4. (a) Comparison of the sensitivity for sufentanil of 50 ng using different shutter modes when the resolving power of IMS was adjusted to be identical. (b) Comparison of the resolution of the two neighboring peaks of methadone of 50 ng using different shutter modes when the peak heights were kept the same.

For the TP ion shutter (Figure 2c), the GCV was applied to G2 and generated by IHV1 floating on V2. When the shutter was closed, only the region between G1 and G2 was depleted. G3 merely worked as a guarding ring. The GCV2 in Figure 2c was set at 800 V to enhance the compression effect. The detailed operation process of TP ion shutter has been described in a previous study.23 For the tristate ion shutter (Figure 2d), the GCV was also applied to G2 and generated by IHV1 and IHV2. IHV1 floated on V2, whereas IHV2 floated on the output potential of IHV1.

potential of G1); therefore, the ion packet was cut off at G2. At timing point t2, the region between G1 and G2 was opened by switching the potential of G2 to V2, whereas the region between G2 and G3 was closed by switching the potential of G3 to the output potential of IHV2. Then, the ions in the reaction region started to fill the left side of the shutter, whereas the injected ions went on moving in the drift region. To ensure that all of the injected ions had passed G3 at timing point t2, t2 − t1 was adjusted to be larger than the penetration time of the slowest ion species to drift from G2 to G3. 9141

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Analytical Chemistry Two high-voltage pulse generators were used to periodically switch the potential of G2 from the output of IHV1 (V1) to close the region between G1 and G2. Because the zones affected by pulsing G2 are too small to cause an obvious effect on the ion packet, the GCV2 and GCV2-1 in Figure 2d were both set at 100 V, slightly higher than the needed voltage to close the shutter. The time difference between t2 and t1 was always set at 500 μs. The detailed shutter operation process is described in ref 21. Under each of the three shutter modes, G1 was kept at constant potential to keep the electric field in the ionization region constant. Materials and Regents. One μg/μL standard stock solutions of illicit drugs in methanol were purchased from Beijing Fenge Science (China), including fentanyl, sufentanil, methamphetamine (MA), methadone, [1-(5-fluoropentyl)-1Hindol-3-yl](naphthalen-1-yl)methanone (AM-2201), 3,4-methylenedioxymethamphetamine (MDMA), ketamine, and cocaine. Sufentanil belongs to the fentanyl analogues, whereas AM-2201 is among the NPSs reported by the largest number of countries and territories.1 Test drug samples were obtained by diluting the standard stock solutions with methanol. Acetone and DMMP of analytical grade were purchased from Kemel Chemical Reagent (Tianjin, China).

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RESULTS AND DISCUSSION Reduction of Mobility Discrimination. To evaluate the mobility discrimination effect under different shutter modes,

Figure 6. IMS plots for the mixture of methamphetamine (MA) of 50 ng, ketamine of 100 ng, and fentanyl of 50 ng in 5 s after swab insertion under (a) dual-compression tristate ion shutter mode, (b) TP ion shutter mode, and (c) tristate ion shutter mode. Before each test, the resolving power for RIP was adjusted to be identical. The sensitivity differences and mobility discrimination differences using different ion shutter modes are clearly visible. Peak assignments: #1 MA monomer, #2 ketamine monomer, #3 MA dimer, #4 fentanyl monomer, #5 MA + ketamine, #6 ketamine dimer, #7 MA + fentanyl, #8 ketamine + fentanyl, and #9 fentanyl dimer.

at tg of 200 μs. As tg decreased from 200 to 70 μs, P3 became increasingly weaker than P1. Finally, P3 disappeared at tg of 60 μs. Under the tristate ion shutter mode, P3 was slightly stronger than P1 at tg of 80 μs. As tg decreased from 80 to 0 μs, P3 even became increasingly stronger than P1. Surprisingly, all three peaks still could be observed at tg of 0 μs. Because the peak intensity had a positive correlation to the quantity of the injected ions, it can be used to intuitively evaluate the mobility discrimination effect of an ion shutter. Therefore, the mobility discrimination effect is strong under the TP ion shutter mode, whereas it can be significantly reduced under the dualcompression tristate ion shutter mode and the tristate ion shutter mode. Because the charge of the injected ions is equal to its peak area, it is more accurate to evaluate the mobility discrimination using its peak area. To compare the peak areas of P1 and P3, the peak area ratio of P3 and P1 (AreaP3/AreaP1) was plotted against tg in Figure 3d. Under the dual-compression tristate ion shutter mode, AreaP3/AreaP1 remained at 1.1 in a wide range of

Figure 5. Gating performance as a function of tg for the three different ion shutters.

DMMP with a stable concentration was measured as the gate opening time (tg) was varied. As displayed in Figure 3a−c, for each ion shutter, three ion peaks can be observed, including the reactant ion peak (RIP, P1), the DMMP monomer peak (P2), and the DMMP dimer peak (P3). Under the dualcompression tristate ion shutter mode, t2 − t1 was set at 110 μs to ensure that all ion species had passed G3 at timing point t2. For a convenient comparison of the intensities of P1 and P3, the intensity of P1 was normalized in each IMS spectrum. Under the dual-compression tristate ion shutter mode, P1 and P3 almost kept the same intensity as tg decreased from 500 to 10 μs. Under the TP ion shutter mode, P3 was weaker than P1 9142

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Figure 7. IMS plots 5 s after sampling swab insertion for six drug mixtures using the dual-compression tristate ion shutter mode. Peak assignments for (a) and (b): #1 cocaine monomer, #2 fentanyl monomer, #3 sufentanil monomer, #4 cocaine + fentanyl, #5 fentanyl dimer, #6 fentanyl + sufentanil, and #7 sufentanil dimer. Peak assignments for (c) and (d): #1 MA monomer, #2 MDMA monomer, #3 MA dimer, #4 MA + MDMA, #5 MDMA dimer, #6 sufentanil monomer, #7 MDMA + sufentanil, and #8 sufentanil dimer. Peak assignments for (e) and (f): #1 MA monomer, #2 MDMA monomer, #3 MA dimer, #4 MA + MDMA, #5 MDMA dimer, #6 AM-2201 monomer, #7 MA + AM-2201, #8 MDMA + AM-2201, #9 (MA)2 + AM-2201, and #10 (MDMA)2 + AM-2201.

tg from 10 to 500 μs. Under the TP ion shutter mode, AreaP3/ AreaP1 was smaller compared with AreaP3/AreaP1 under the dual-compression tristate ion shutter mode and decreased from 0.8 to 0 as tg decreased from 200 to 60 μs. Under the tristate ion shutter mode, AreaP3/AreaP1 was similar to that under the dual-compression tristate ion shutter mode at tg of 80 μs and then increased from 1.1 to 1.7 as tg decreased from 80 to 0 μs. Supposing that d is the position difference of the starting line and cutting off line of an ion packet in the injection process, then d affects the amount of the injected ions and hence is related to the mobility discrimination effect. Therefore, the peak area ratio of P3 and P1 can be expressed as a function of d and tg as AreaP3

=

AreaP1 =

(K3Etg − d) ·S ·N3

K3N3 ijj K − K3 d jj1 − 1 · j j K1N1 K3 K1Etg − k

(K1Etg − d) ·S ·N1

=

yz zz z d zz {

tg was, the more serious the discrimination effect got. Under the tristate ion shutter mode, AreaP3/AreaP1 increased with the decrease in tg, meaning that d < 0 and the starting line was ahead of the cutting off line. Therefore, ions in the shutter region could not be completely discharged at the closed state of shutter, leading to not only the elimination of the discrimination effect but also the detection of ions at tg of 0 μs. Furthermore, the value of d could be calculated as 9 μm in the dual-compression tristate ion shutter, 870 μm in the TP ion shutter, and −335 μm in the tristate ion shutter using the gate opening widths necessary to inject a charge of zero (Figure S-1). These values are in good agreement with the predictions made based on the measurements shown in Figure 3. Notably, by making the starting line coincide with the cutting off line, the dual-compression tristate ion shutter also made the peak area truly reflect the ion density according to eq 1. Something abnormal in Figure 3d is that the peak area ratios did not converge to the same value. That is probably caused by the DMMP concentration variations with the fluctuations in ambient temperature. Improvement of Gating Performance. To examine the performance of the miniaturized IMS apparatus in drug screening, sufentanil of 50 ng and methadone of 50 ng were detected under three shutter modes, as shown in Figure 4a,b, respectively. Before each test of sufentanil, the resolving power for RIP was adjusted to be identical at 63 by setting tg at 190, 100, and 30 μs for the dual-compression tristate ion shutter, the TP ion shutter, and the tristate ion shutter, respectively. The difference between t2 and t1 was set at 230 μs under dualcompression tristate ion shutter mode to ensure that all ion

(K3Etg − d) ·N3 (K1Etg − d) ·N1

(1)

where S is the sectional area of the injected ion packets, E is the electric field strength, K1 and K3 are the ion mobilities, and N1 and N3 are the ion densities of the two ion species, respectively. Under the dual-compression tristate ion shutter mode, AreaP3/AreaP1 remained constant with the variation in tg, meaning that d = 0 and the starting line coincided with the cutting off line. Therefore, the discrimination effect could be eliminated. Under the TP ion shutter mode, AreaP3/AreaP1 decreased with the decrease in tg, meaning that d > 0 and the starting line fell behind the cutting off line. Hence, the shorter 9143

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(>67) over a broad tg range from 140 to 440 μs, providing easier parameter optimization for an IMS instrument. Again, this is due to the two times of compression on the injected ion packet in the dual-compression tristate ion shutter. Notably, for small tg values, the resolving power remained nearly constant even as tg got shorter, which is probably limited by both the diffusional broadening and the response speed of the preamplifier (Figure S-1). Detection of Fentanyl Drug Mixtures. To examine the performance of the miniaturized IMS apparatus in the screening of fentanyl drug mixtures, 50 ng of MA, 100 ng of ketamine, and 50 ng of fentanyl were mixed and then detected under different shutter modes, with the results shown in Figure 6. Again, the resolving power for RIP was adjusted to be identical at 63 before each test by setting tg at 190, 100, and 30 μs for the dual-compression tristate ion shutter, the TP ion shutter, and the tristate ion shutter, respectively. The difference between t2 and t1 was set at 230 μs under the dual-compression tristate ion shutter mode to ensure that all ion species had passed G3 at timing point t2. Under the dual-compression tristate ion shutter mode, nine drug peaks with 1/K0 ranging from 0.634 to 1.356 s V cm−2 were observed and numbered 1− 9 (Figure 6a). According to tests of each drug standard and each mixture of any two of the three drugs, the nine peaks were assigned to three drug monomers (#1 MA monomer, #2 ketamine monomer, #4 fentanyl monomer), three drug dimers (#3 MA dimer, #6 ketamine dimer, #9 fentanyl dimer), and three drug complexes (#5 MA + ketamine, #7 MA + fentanyl, #8 ketamine + fentanyl). Under the TP ion shutter mode, only peaks numbered from 1 to 7 were observed, whereas the two slowest ions (ketamine + fentanyl and fentanyl dimer) were undetectable due to the mobility discrimination effect of the TP ion shutter (Figure 6b). Under the tristate ion shutter mode, all nine drug ions were detected (Figure 6c), whereas their peaks were weaker than half of their peaks under the dualcompression tristate ion shutter mode. Obviously, the observation of every drug complex and drug dimer is beneficial to the identification of the constituents of the drug mixture. By compressing the injected ion packet twice and eliminating the mobility discrimination effect, the dual-compression tristate ion shutter enhances both the sensitivity of the IMS and the identification accuracy of ketamine and fentanyl in the mixture. To further demonstrate the ability of the miniaturized IMS apparatus to screen drug mixtures, 50 ng of fentanyl, sufentanil, or AM-2201 was mixed into 50 ng of different traditional drugs, including cocaine, MA, and MDMA, and then detected under dual-compression tristate ion shutter mode (Figure 7). Including the RIP, the product ion peaks spread a broad range of 1/K0 from 0.492 to 1.552 s V cm−2, which corresponded to a K0 range from 0.644 to 2.032 cm2 s−1 V−1. Through detecting each drug standard and each mixture of any two drugs, the peaks were assigned to the monomer ions, dimer ions, and complex ions of the drugs. Among them, four ions are even slower than the fentanyl dimer, including fentanyl + sufentanil (1/K0 = 1.381 s V cm−2), sufentanil dimer (1/K0 = 1.415 s V cm−2), (MA)2 + AM-2201 (1/K0 = 1.520 s V cm−2), and (MDMA)2 + AM-2201 (1/K0 = 1.551 s V cm−2). The sensitive detection of various drug ions further verified the effectivity of the dual-compression tristate ion shutter-equipped miniaturized IMS apparatus in the screening of drug mixtures. In this work, the sensitivity was enhanced through improving the ion injection and transport process. Because the limit of detection (LOD) is also related to the ion source design and the sample

species had passed G3 at timing point t2. The dualcompression tristate ion shutter improved the intensity of RIP by 40% compared with the TP ion shutter and 150% compared with the tristate ion shutter. Under the dualcompression tristate ion shutter mode, two peaks of sufentanil were observed, assigned to sufentanil monomer and sufentanil dimer. The two peaks were 48 and 37% of the RIP height, respectively. Under the TP ion shutter mode, a weak peak of sufentanil monomer only 10% of the RIP height was observed, whereas the sufentanil dimer was undetectable. Under the tristate ion shutter mode, both the monomer peak and the dimer peak of sufentanil were observed, and the two peaks were 49 and 41% of the RIP height, respectively. Clearly, the dual-compression tristate ion shutter eliminated the mobility discrimination effect almost as effectively as the tristate ion shutter. Besides, by compressing the ion packet twice during the injection process, the dual-compression tristate ion shutter mode surpassed the other two shutter modes in sensitivity for sufentanil, which also enhanced the observation of the dimer ion and hence contributed to the accurate identification of sufentanil. Notably, none of the previous studies relating to the IMS-analysis of fentanyl or its analogues has reported any dimer peak.27−30 In the tests of methadone, two neighboring peaks were observed. The tg was adjusted to 140, 195, and 90 μs for the dual-compression tristate ion shutter, the TP ion shutter, and the tristate ion shutter, respectively, to obtain identical peak heights. Under dual-compression tristate ion shutter mode, t2 − t1 was set at 135 μs. After peak fitting, the resolution of the two peaks was calculated via eq 2 resolution =

1.18 × (1/K 02 − 1/K 01) wh1 + wh2

(2)

where K01 and K02 are the reduced ion mobilities of the two peaks; wh1 and wh2 are the full widths at half-maximum of the two peaks. The resolution of the two peaks was 1.02, 0.86, and 0.70 under the dual-compression tristate, the TP ion shutter, and the tristate ion shutter modes, respectively. The dualcompression tristate ion shutter improved the resolution by 19% compared with the TP ion shutter and 46% compared with the tristate ion shutter. The reason for the resolution improvement was also due to the two times of compression on the injected ion packet. To systematically compare the three shutters, their gating performances calculated from the single acetone dimer peak are plotted against tg in Figure 5. For the dual-compression tristate ion shutter, t2 − t1 was set at 100 μs. The gating performance had been defined to comprehensively evaluate an ion shutter as23 gating performance = resolving power ×

peak height TIC

(3)

where TIC is the total ion current. Obviously, the tristate ion shutter was superior to the other two shutters at a short tg (0 to 40 μs); however, it had the lowest best gating performance among the three shutters. The best gating performance of the dual-compression tristate ion shutter (127, obtained at tg of 420 μs) was about two times the best gating performance of the TP ion shutter (58, obtained at tg of 140 μs), and about three times the best gating performance of the tristate shutter (43, obtained at tg of 50 μs). Besides, the dual-compression tristate ion shutter exhibited outstanding gating performance 9144

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Analytical Chemistry desorption process, it can be further reduced by improving the ion source and accelerating the thermal desorption process.

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ACKNOWLEDGMENTS

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REFERENCES

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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.9b01700. Figure S-1. Plots of the measured fwhm, resolving power, and total charge for the acetone dimer peak as a function of gate opening time obtained using three different ion shutter modes (PDF)

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This work was supported by the National Key R&D Program of China (project nos. 2016YFC0201200 and 2016YFC0800912), National Natural Science Foundation of China (grant nos. 21405158 and 21707138), Dalian Institute of Chemical Physics (grant nos. DICP ZZBS201709, DICP ZZBS201801, and DICPZZBS201808), and Scientific Study Project of Liaoning Province Educational Commission of China (grant no. LQ201715001). Dedicated to the 70th anniversary of the Dalian Institute of Chemical Physics, CAS.

CONCLUSIONS With a 38.9 mm long drift region, the miniaturized IMS instrument achieved a resolving power of not less than 63. Owing to reduction of ion discrimination and two times of compression on the injected ion packet, the dual-compression tristate ion shutter helps the miniaturized IMS instrument improve the sensitivity in drug screening without reducing the resolving power. For example, the peak height was improved by 40% compared with the TP ion shutter and 150% compared with the tristate ion shutter when the resolving power was the same; the resolution of neighboring peaks was improved by 19% compared with the TP ion shutter and 46% compared with the tristate ion shutter when the peak heights were the same. As a result of the sensitivity and resolving power enhancement, the best gating performance of the dualcompression tristate ion shutter was three times that of the tristate ion shutter and two times that of the TP ion shutter. In the screening of drug mixtures, the miniaturized IMS is much more sensitive for drug ions spreading a wide ion mobility range from 0.644 to 2.032 cm2 s−1 V−1 under the dualcompression tristate ion shutter mode than under the other two shutter modes. In addition, the dual-compression tristate ion shutter can enhance the ability to observe the complex ions or dimer ions in IMS spectra, which helps us to accurately identify the different constituents in the drug mixtures. It can be speculated that the dual-compression tristate ion shutter could also enhance the performance of IMS devices in the detection of explosive mixtures or substances that produce large ions prone to be discriminated by general ion shutters; however, the dual-compression ion shutter might cause error in calculating the mobility based on arrival time because ions of different mobilities would have traveled different distances away from the ion shutter when the field behind G3 was strengthened by GCV3 at timing point t2.

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Article

AUTHOR INFORMATION

Corresponding Authors

*H.L.: Fax: +86-411-84379517. E-mail: [email protected]. *C.C.: Fax: +86-411-84379517. E-mail: [email protected]. cn. ORCID

Haiyang Li: 0000-0002-6658-4745 Author Contributions

The manuscript was written through contributions of all authors. All authors have given approval to the final version of the manuscript. Notes

The authors declare no competing financial interest. 9145

DOI: 10.1021/acs.analchem.9b01700 Anal. Chem. 2019, 91, 9138−9146

Article

Analytical Chemistry (29) Hollerbach, A.; Fedick, P. W.; Cooks, R. G. Anal. Chem. 2018, 90, 13265−13272. (30) Zaknoun, H.; Binette, M.-J.; Tam, M. Int. J. Ion Mobility Spectrom. 2019, 22, 1−10.

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DOI: 10.1021/acs.analchem.9b01700 Anal. Chem. 2019, 91, 9138−9146