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Enhancing the sensitivity of ion mobility spectrometry using the ion enrichment effect of non-uniform electrostatic field
Sensors & Actuators: B. Chemical 295 (2019) 179–185
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Sensors and Actuators B: Chemical journal homepage: www.elsevier.com/locate/snb
Enhancing the sensitivity of ion mobility spectrometry using the ion enrichment effect of non-uniform electrostatic field Chuang Chena, Hong Chena,b, Dandan Jianga, Mei Lia,b, Wei Huanga, Haiyang Lia,
T
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a CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, People’s Republic of China b University of Chinese Academy of Sciences, Beijing, 100039, People’s Republic of China
A R T I C LE I N FO
A B S T R A C T
Keywords: Ion mobility spectrometry Sensitivity Non-uniform electrostatic field Ion enrichment SIMION simulation
The diversified applications of ion mobility spectrometry (IMS) frequently pose challenges to the sensitivity of IMS measurements. In this work, the ion density evolution profiles of a continuous flow of ions travelling in nonuniform electrostatic fields were studied. Based on that, an ion enrichment method was proposed for enhancing the sensitivity of IMS. It employed a gradually weakening electrostatic field in the ionization region of IMS and achieved ion density enhancement for the ion flow migrating from the ion source to the ion shutter. Using that method, the ion density of the ion flow produced by the ion source was increased by 180% when approaching the ion shutter. With the increased ion density, the limit of detection (LOD) for DMMP dimer peak was lowered from 425 to 200 pptv. Meanwhile, there was a slight reduction in the resolving power, which was tentatively assigned to the enhanced coulomb repulsion along with the increased ion density. The resolving power of the IMS with a drift length of 60 mm was still maintained around 80 at 100 degrees Celsius. The ion enrichment method needs no radial-confining radio frequency voltage. Also, it does not affect the response speed of IMS.
1. Introduction Ion mobility spectrometry (IMS) is a gas-phase ion separation and detection technique based on the ion mobility (K0) differences among ions in an electric field [1]. It plays a key role in security screening sensors targeting at explosives, narcotics and chemical warfare agents [2–4]. Much of that success is attributed to its satisfactory features: fast response, good portability, low cost and moderately high sensitivity at ambient pressure. Moreover, the capabilities of IMS to work at either ambient pressure or sub-ambient pressure and to combine with different ambient ion sources have opened avenues for applications in many other areas of analytical chemistry. As a standalone monitoring tool, IMS has been used for pharmaceutical [5], food [6], clinical [7] and environmental analyses [8]. When hyphenated to gas chromatography (GC) or mass spectrometry (MS), IMS offers an additional separation dimension to GC or MS and has been extensively used to characterize analytes in complex matrixes [9,10]. These diversified applications, however, frequently pose challenges to the sensitivity of IMS with direct sample introduction system, especially as the concentrations of target analytes go down to sub-ppbv or sub-ng levels. Sample preconcentration is widely used to improve the sensitivity of IMS measurements. Typical methods for pretreating samples before
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introducing them to IMS include dispersive liquid-liquid microextraction (DLLME), solid-phase extraction (SPE), and solid-phase microextraction (SPME) [11]. Arce et al. [12] coupled a Tenax TA trap column to photoionization ion mobility spectrometer and achieved sensitive detection of BTEX present in gaseous samples. The limit of detection (LOD) for benzene and toluene was lowered to 0.54 and 0.57 mg/m3, respectively. Recently, these sample pretreatment methods begin to combine with various smart sorbents, such as immunosorbents, molecularly imprinted polymers, and nano-materials, and demonstrate very high efficiency in selective extraction and enrichment of target analytes from complex matrices [13]. As reported by Tabrizchi et al. [14], using Au-NPs-thiol silane film/SPME fiber coupled to corona discharge IMS, acetone of 1 pptv in human breath was measured. Sample preconcentration, however, usually takes a long time ranging from several minutes to tens of minutes, which might reduce the analysis throughput of IMS, especially for field screening IMS devices. IMS is typically a pulsed analytical technique. Improving its duty cycle could effectively enhance the ion signals of IMS for analysis of complex mixtures. One method to improve the duty cycle is temporal multiplexing, where the ion shutter of IMS is operated using multiple time-dispersive pulses within a single data acquisition cycle. Fourier
Corresponding author. E-mail address: [email protected] (H. Li).
https://doi.org/10.1016/j.snb.2019.05.088 Received 19 February 2019; Received in revised form 23 May 2019; Accepted 24 May 2019 Available online 25 May 2019 0925-4005/ © 2019 Elsevier B.V. All rights reserved.
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[15], Hadamard [16], and Cross-correlation [17] sequences have all been employed to generate an overlapped mobility spectrum and then retrieve a single time-dispersion spectrum via deconvolution. Using temporal multiplexing, the duty cycle of IMS could be increased up to 50%. As reported by Hill et al. [15], the enhanced duty cycle led to a signal-to-noise ratio (SNR) gain of around 10 comparing to conventional IMS. Not only the sensitivity, temporal multiplexing is also good for IMS to achieve high resolving power. Clowers et al. [17] used Crosscorrelation to obtain a SNR gain of 8 and meanwhile push the resolving power of IMS close to its theoretical value. However, temporal multiplexing in IMS usually requires stable ion source and sample introduction during the data acquisition circle for achieving better SNR gains. That is not practical for field screening IMS or online monitoring IMS devices. Besides, due the imperfect gating performance and the ion depletion effect of ion shutters in IMS, there always are false peaks resulting from modulation defects, which researchers are still trying to eliminate. Another method to improve the duty cycle of IMS is the use of an ion trap device before each IMS experiment to accumulate the ions produced by the ionization source while the last ion packet is separated in the drift region, then the stored ions are pulsed into the drift region of IMS for the next data acquisition cycle. Clemmer et al. [18] reported a method of using the ion funnel trap (IFT) in a cyclical drift tube IMS-MS experiment. The IFT was demonstrated to improve the duty cycle from 0.2% to 25%, allowing the observation of ions travelled over 100 cycles around the cyclotron where a resolving power in excess of 1000 was achieved for separating a mixture of peptides with similar mobilities. Recently, Smith et al. [19] reported a compression ratio ion mobility programming (CRIMP) approach to accumulate and compress ions for IMS-MS analysis. That enhanced the LOD for peptides and provided an 100-fold increase in sensitivity compared to their previous work using an IFT. However, these above designs usually require a working pressure of several millibar and a radial-confining RF voltage. They are not compatible with standalone or hyphenated IMS devices working at atmospheric pressure since ions cannot be effectively transferred across the high-pressure differential of the interface. Spatial ion packet compression based on electric field switching has also been used to improve the sensitivity of IMS measurements. It employs a high voltage pulse to enhance the electric field in a spatially confined region during the ion shutter opening period. Thereby, the packet of ions existing in that region would be compressed into the drift region of IMS and form a narrower ion packet with higher ion density. Finally, an ion peak with high signal to noise is observed. Using that method, an field switching (FS) ion shutter for efficient ion injection was developed by Jenkins [20] and Leonhardt et al. [21]. Gunzer et al. [22] used the FS ion shutter to efficiently pulse the ions generated by a non-radioactive electron source into the drift region of IMS. Kirk et al. [23] further used the FS ion shutter to develop a compact IMS possessing high sensitivity (reaching pptv level) and high resolving power (reaching 183). Besides, Li et al. [24] also combined the FS ion shutter with Bradbury-Nielsen gate (BNG) for injecting more ions into the drift region during the BNG opening interval. Even all these techniques target at spatially confined ion packets and involve electric field switching, the spatial ion packet compression is actually subject to the non-uniform electric field induced by the high voltage pulse. As Gunzer et al. [25] explained, for an ion packet moving in a gradually weakening electric field, its trailing edge moves faster than its leading edge, causing its spatial width reduced and ion density increased. The underlying principle of the spatial ion packet compression inspires us to further explore the ion density evolution of a continuous flow of ions in non-uniform electrostatic fields, especially the flow of ions drifting in the ionization region of IMS, which is important for designing IMS with high sensitivity. The aim of this work is to propose an ion enrichment method based on non-uniform electrostatic field for enhancing the sensitivity of IMS measurements. For that purpose, the influence of electrostatic field on the movement behavior of a
Fig. 1. Illustration of the spatial width and the ion density evolutions of ions travelling under different electrostatic fields.
continuous flow of ions was mathematically elucidated first, followed by a simulation validation using the SDS model of SIMION software. It was found that, ions from the ion source could be enriched or diluted while migrating towards the ion shutter by simply applying a gradually decreasing or enhancing electrostatic field along the ion drift direction in the ionization region of IMS, which was further experimentally proved. On that basis, the performance of the proposed method in improving the sensitivity of IMS was demonstrated. 2. Mathematical elucidation for ions travelling under electrostatic fields As displayed in Fig. 1, at timing start point t = 0, a packet of positive ions with a mobility K, an initial ion density n, and an initial spatial width δ is about to travel along the x direction in a positive electrostatic field E(x) (E/N < 2 Td, 1 Td = 10−17 V·cm2), resembling the field in the ionization region of the IMS. Considering the electric field as the only factor that influences the ion transport, the time difference for the trailing edge and the leading edge of the ions to arrive at x = d (d > δ) could be expressed as
Δti = ttrailing − tleading = =
∫0
d
dx − K ⋅E (x )
∫δ
d
δ K ⋅E (ξ )
dx = K ⋅E (x )
∫0
δ
dx K ⋅E (x ) (1)
where, ξ is a value on the x-axis which meets 0 < ξ < δ and the Lagrange’s Mean Value Theorem. Assume the leading edge of the ion packet keeps travelling under electric field E(d) after it arrives at x = d, when the trailing edge arrives, the spatial width δi and the ion density ni of the ion packet goes beyond x = d could be expressed as
δi = K ⋅E (d )⋅Δti = K ⋅E (d)
ni =
δ E (d ) = δ K ⋅E (ξ ) E (ξ )
E (ξ ) E (0) n⋅S⋅δ δ n≈ n = n= E (d ) E (d ) S⋅δi δi
(2)
(3)
where, S is the cross section of the ion packet perpendicular to the x direction. Making the initial width (δ) of the ion packet infinitely close to 0, the E(ξ) in Eq. (3) could be further approximately expressed as E (0). In fact, an infinite number of ion packets being generated successively in the time domain are actually a continuous flow of ions. Thus, Eq. (3) could also be used to depict the ion density evolution of a continous flow of ions travelling in E(x). Here, an ion enrichment factor ηn defined as ni divided by n is proposed to evaluate how the ion density 180
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would evolve for a continous flow of ions travelling in E(x), as show by Eq. (4).
ηn =
ni E (0) ≈ n E (d )
Grid 2 of the TPG while maintaining the potentials on all the other electrodes unchanged. Specifically, at the TPG open status, potentials of 2900, 2500, 2100, 1700, 1300, 900, 500, 400, and 0 V are applied to Plate 1, Ring 1, Ring 2, Ring 3, Ring 4, Ring 5, Grid 1, Grid 2, and Plate 2, forming an electric field along the x direction in the ionization and the drift regions. As the potential difference between Grid 1 and Grid 2 (defined as the gate penetration voltage, GPV) is 100 V, the x-component of the electric field Ex (Ex = -∂V/∂x) in the gate region is along the x direction (Ex > 0), allowing positive ions to go through the TPG. To closed the TPG, an extra voltage of 250 V (defined as the gate closing voltage, GCV) is superposed on the original potential (400 V) of Grid 2, while the potentials on all the other electrodes are maintained unchanged. The direction of the Ex in the gate region is reversed (Ex < 0), preventing positive ions from going through the TPG. Using the above IMS working mode, the movement behaviors of ions under the influence of the electric field in the ionization region during the TPG opening and closing interval was studied. At timing start point t =0 μs when the TPG is open, 5000 acetone dimer ions ((Ac)2H+ with SIMION estimated K0 of 2.3 cm2V−1s−1) randomly distributed in a cylindrical volume of 8 mm in diameter and 10 mm in length are generated at the top of the ionization region, as demonstrated by the green dots in Fig. 2a. Under the force of the electric field, the ions move with size unchanged till their leading edge approached the TPG, as demonstrated by the red dots in Fig. 2a. Similar phenomenon is observed when applying a GCV to close the TPG, as displayed by Fig. 2b. With the size unchanged, the ions move towards the TPG with no changing in the ion density. As closing the TPG, simultaneously changing the voltage difference between Ring 5 and Grid 1 (defined as the ion enrichment voltage, IEV) but maintaining the potential differences between any other two adjacent electrodes in the ionization region at 400 V, different size evolution profiles could be observed. As displayed by Fig. 2c, with the IEV varied to 100 V, the ions get compressed along the x direction as moving towards the TPG, forming a size smaller than their initial size. While, with the IEV varied to 700 V, the ions get elongated along the x direction as moving towards the TPG, forming a size bigger than their initial size, as displayed by Fig. 2d. A change in the size corresponds to a change in the ion density; the ions get enriched at the IEV of 100 V
(4)
Obviously, ηn is subject to the ratio of E(0) versus E(d). (1) If ∂E(x)/ ∂x = 0, then E(x) ≡ E(0) and ηn = 1, indicating the ion flow will keep its ion density in uniform electrostatic field no matter how distant it travels. (2) If ∂E(x)/∂x ≠ 0, then the ion packet travels in an non-uniform electrostatic field; There are three situations: (a) When E(0) < E (d), then ηn < 1, the ion flow is diluted; the smaller the value of ηn is, the lower the ion density gets. (b) When E(0) = E(d), ηn = 1, the ion flow would keep its ion density even in non-uniform electrostatic field. (c) When E(0) > E(d), ηn > 1, the ion flow is enriched; the bigger the value of ηn is, the higher the ion density gets. 3. SIMION simulation of ions drifting in the ionization region The movement behaviors of ions under the influence of different electrostatic fields in the ionization region of IMS were explored using the SDS model of SIMION software at 100 degrees Celsius. The repulsion between ions was not considered and the geometry of the IMS drift tube was simplified as described below. As displayed in Fig. 2a, two round electrodes with thickness of 0.94 mm and diameter of 30 mm, Plate 1 and Plate 2, are positioned in parallel at x = -1.00 mm and x = 36.06 mm, confining a space resembling the IMS drift tube. A Tyndall-Powell gate (TPG) comprised of two 0.06 mm-thick grids, Grid 1 and Grid 2, is placed between the two round electrodes, separating the space into three regions: the ionization, the gate, and the drift regions. The grids are positioned in parallel at x = 29.94 mm and x = 31.00 mm, keeping a grid-to-grid distance of 1 mm. The two grids are identical wire grids, having parallel square wires with side length of 0.06 mm and a wire-to-wire distance of 0.60 mm, as used in the following experiments. Five annular electrodes, Rings 1–5, are co-axially placed in the ionization region, cutting it in to six even zones. The rings are of 0.06 mm thick, having an inner diameter of 15 mm and an outer diameter of 30 mm. The IMS usually works with a periodical voltage pulse applied to
Fig. 2. Movement behaviors of acetone dimer ions in the ionization region of the IMS at 100 degrees Celsius. (a) The Tyndall-Powell gate (TPG) is open. In the ionization region, the potential differences between any two adjacent electrodes are maintained at 400 V. (b) The TPG is closed. Only an extra voltage of 250 V (defined as the gate closing voltage, GCV) is superposed on the original potential (400 V) of Grid 2 for closing the TPG, the potentials on all the other electrodes are maintained. (c) The TPG is closed. As closing the TPG, the potential difference between Ring 5 and Grid 1 (defined as the ion enrichment voltage, IEV) is reduced to 100 V, but the potential differences between any other two adjacent electrodes in the ionization region are maintained at 400 V. (d) The TPG is closed. As closing the TPG, the IEV is increased to 700 V, but the potential differences between any other two adjacent electrodes in the ionization region are maintained at 400 V. For each case, the distribution profiles of the ions at the timing start point t = 0 μs (green dots) and when its leading edge approached the TPG (red dots) are recorded. All the black rectangles are of the same size (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article). 181
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Fig. 3. Ex versus x plot along the axis of the IMS drift tube (y = 0 mm) at the TPG open status and Ex versus x plots along y = 0 mm at the TPG closed status with varying the IEV from 0 to 700 V. The GPV stands for the gate penetration voltage defined as the voltage difference between Grid 1 and Grid 2 at the TPG open status, while the GCV stands for the gate closing voltage defined as the extra voltage superposed on the original potential (400 V) of Grid 2 for closing the TPG.
Fig. 4. Schematic of the Tyndall-Powell gate (TPG) ion mobility spectrometer (top) and the voltage controlling scheme (bottom) for studying the effect of non-uniform electrostatic field on ions drifting in the ionization region. The IEE stands for the ion enrichment electrode. The voltage pulse for Grid 2 is for controlling the TPG to open for an interval (GPW) in every 30 ms. The voltage pulse for IEE, having a period of 30 ms and a duty cycle of 50%, is for maintaining the potential difference between IEE and Grid 1 at 400 V when the TPG is open and changing the potential difference between IEE and Grid 1 (defined as the ion enrichment voltage, IEV) to a value of 0–700 V when the TPG is closed. Note, the delay time (dt) between the two pulses is normally set at 0 μs without specific notification.
up from 80 V/mm to a plateau along the x direction; the bigger the IEV is, the higher the plateau is. Oppositely, decreasing the IEV to be smaller than 400 V, the Ex value gradually goes down from 80 V/mm to a valley along the x direction; the smaller the IEV is, the deeper the valley is. Similar phenomena could be observed for some other y lines, as displayed in Figure S1. At ambient pressure, the ion drift velocity is proportional to the electrostatic field (E/N < 2 Td) [1]. In an uniform field, the ions of the same K0 in the ionization region possess the same drift velocity, ensuring them to move towards the TPG with no changing in the ion density distribution profile. While, in a gradually weakening or strengthening electric field, the ions of the same K0 at different locations of the ionization region possess different drift velocities; some ions
and diluted at the IEV of 700 V while drifting towards the TPG. To explain the movement behaviors of the ions in the ionization region as discussed above, the Ex values inside the IMS drift tube at the TPG open status and at the TPG closed status with varying the IEV from 0 to 700 V were recorded. Fig. 3 displays the evolution profiles of the Ex versus x plot along the axis of the IMS drift tube (y = 0 mm) at the TPG open and closed statuses. Clearly, at the TPG open status, the Ex versus x plot has uniform Ex values of 80 V/mm in the ionization region, as shown by the black plot in Fig. 3. However, at the TPG closed status, the IEV value markedly affects the Ex distribution profile in the ionization region. With the IEV maintained at 400 V, the Ex values in the whole ionization region keep nearly intact, as shown by the red plot in Fig. 3. Increasing the IEV to be higher than 400 V, the Ex value gradually goes 182
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collected by the faraday cup was amplified via a two-stage pre-amplifier with a gain of 109 V/A and a bandwidth of 41 kHz. The output of the pre-amplifier was fed to an oscilloscope (Tektronix, 2024C, U.S.) for spectra recording. Each recorded spectrum was the average of sixteen original spectra. Compressed air purified by activated carbon, silica gel, and fresh molecular sieves was fed into a pneumatic system to generate drift, dopant, and sample gases at flow rate of 100, 5, and 5 mL·min−1, respectively, as represented in Figure S2. The humidity of the purified air was below 1 ppmv. The gases were all preheated to 100 degrees Celsius before entering the drift tube. Acetone and DMMP (dimethylmethylphosphonate) of analytical grade were used as dopant and analyte, respectively. They both were introduced into the pneumatic system via online permeation and purging. The acetone dopant gas with a concentration above 20 ppmv was used to react with most of the reactant ions in the 63Ni source and form a single product ion peak. The DMMP sample gas at different concentrations generated via online dilution was used to test the sensitivity of the IMS. For safety consideration, active carbon traps were used to capture acetone and DMMP from the gas outlets of the IMS and the pneumatic system to prevent environmental pollution. All the power supplies were operated only by trained personnel.
move fast and some ions move slow, forcing them to aggregate or segregate while moving towards the TPG. And, the stronger the weakening or the strengthening is, the more prominent the aggregation or the segregation would become. This matches the prediction of the mathematical model proposed above. The movement behaviors of the ions displayed in Fig. 2 could thus be explained. Based on the above understandings, in practical IMS, by applying heterogeneous electrostatic fields in the ionization region during the TPG closed interval and switching them back to exactly the same uniform field during the TPG open interval, there is possibility to explore the effect of non-uniform electrostatic field on the ion density evolution of a continuous flow of ions. To do that, it is necessary to have an ion source which generates constant flow of ions. 4. Experimental section The Tyndall-Powell gate (TPG) ion mobility spectrometer used in this work was constructed at our laboratory, as schematically displayed in Fig. 4 (top). The IMS cell comprised a faraday cup, a drift region of 60 mm long, a TPG, an ionization region of 30 mm long, and a 10 mCi cylindrical 63Ni source. The drift region and the ionization region were both confined by alternatively stacked stainless steel rings (each 0.06 mm thick) and teflon rings (each 4.94 mm) with an outer diameter of 30 mm. The inner diameters of the drift region and the ionization region were 24 mm and 15 mm, respectively. The TPG comprised two identical wire grids of 0.06 mm thick separated by a teflon ring of 1 mm thick. The grids were made of stainless steel, having parallel square wires with side length of 0.06 mm and wire-to-wire distance of 0.6 mm. The wires spanned a hole of 15 mm in diameter on a disc of 30 mm in diameter. The ion source was placed between a round electrode and a wire grid the same as the one used for making the TPG. A high voltage power supply (HV0) and a resistor chain were used to fix the potential of Grid 1 at 5300 V (V1) and the potential of Grid 2 at 5200 V (V0) while the TPG was open, meanwhile forming an uniform potential difference of 400 V for any adjacent electrodes in the drift region. The potential difference, V1 - V0, was defined as the gate penetration voltage (GPV) and the GPV was fixed at 100 V. A first isolated high voltage power supply (IHV1) with an output of 250 V floating on the potential V0 and a first high voltage pulse generator (DEI, PVX4110, U.S.) were used to produce a voltage pulse for Grid 2, as shown by the red voltage wave in Fig. 4 (bottom). The voltage pulse for Grid 2 periodically varied between V0 and V2 so as to control the TPG to open for an interval (gate opening pulse width, GPW) every 30 ms. The potential difference, V2 - V0, was defined as the gate closing voltage (GCV) and the GCV was fixed at 250 V. A second isolated high voltage power supply (IHV2) with an fixed output of 400 V floating on the potential V1, a third isolated high voltage power supply (IHV3) with an adjustable output of 0–700 V floating on the potential V1, and a second high voltage pulse generator (DEI, PVX-4110, U.S.) were used to produce a voltage pulse for the electrode in the ionization region which was adjacent to Grid 1 (named as the ion enrichment electrode, IEE), as shown by the blue voltage wave in Fig. 4 (bottom). The voltage pulse for IEE, having a period of 30 ms and a duty cycle of 50%, was for maintaining the potential difference between IEE and Grid 1 at 400 V when the TPG was open and changing the potential difference between IEE and Grid 1 (defined as the ion enrichment voltage, IEV) to a value of 0–700 V when the TPG was closed. The voltage pulse for IEE and the voltage pulse for Grid 2 were normally synchronized. Their rising and falling edges were all less than 100 ns. Specifically, a delay time (dt) between them, as shown in Fig. 4 (bottom), could also be set for screening the ion density distribution profiles in the ionization region. A fourth isolated high voltage power supply (IHV4) with an output of 2400 V floating on the potential of IEE was used to form an uniform potential difference of 400 V for all the other adjacent electrodes in the ionization region, no matter the TPG was open or closed. The IMS cell was kept at 100 degrees Celsius. The ion current
5. Results and discussion 5.1. Ion enrichment and ion dilution effects To see how the IEV affects the movement behavior of ions in the ionization region, the spectra of acetone dimer ions at the GPW of 6 ms were obtained as varying the IEV from 0 to 700 V. As displayed in Fig. 5, with the IEV varying from 0 to 700 V, the trailing edges of all the ion current curves superpose well, while the leading edges show very different height changing patterns. At the IEV of 400 V, the ion current curve shows a nearly square leading edge, which quickly reaches the flat TIC level. Decreasing the IEV to be lower than 400 V, the leading edge firstly shoots up to be higher than the TIC level and then gradually goes down to the TIC level; and, the lower the IEV is, the higher the leading edge is. On the contrary, increasing the IEV to be higher than 400 V, the leading edge firstly shoots up to be lower than the TIC level and then gradually goes up to the TIC level; and, the higher the IEV is, the lower the leading edge is. Siems et al. [26] pointed out that the leading edge of an ion bundle moving in the drift region remains the ion distribution features in the ionization region adjacent to the ion shutter. As the experimentally measured ion current is proportional to the ion density, the leading edge of the ion current curve shown in Fig. 5 exactly reflects the ion
Fig. 5. Spectra of acetone dimer ions obtained at a GPW of 6 ms with the IEV varying from 0 to 700 V. The TIC stands for the total ion current obtained with the 63Ni ion source using acetone as dopant at the TPG fully open mode. 183
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for the ideal uniform distribution case.
density distribution profile in the ionization region adjacent to the TPG. At the IEV of 400 V, the ions in the whole ionization region share nearly the same ion density. While, as the IEV deviating from 400 V, the ions in the ionization region begins to possess a gradually increasing (IEV < 400 V) or decreasing (IEV > 400 V) ion density along the ion drift direction; And, the more the deviation is, the more the increment or the decrement is. That phenomenon is named as the ion enrichment and ion dilution effects. Considering the facts that varying the IEV at the TPG closed status does not affect the electric field in the vicinity of the 63Ni ion source (see Fig. 3) and the rising or falling edge of the voltage pulse on IEE does not affect the movement of ions in the ionization region (see Figure S3), the ion enrichment and ion dilution effects are mainly achieved by the IEV induced non-uniform electrostatic field in the ionization region during the TPG closing period, as discussed in the SIMION simulation section.
5.3. Sensitivity and resolving power To explore the influence of the ion enrichment effect on the sensitivity and the resolving power of the IMS, the delay time between the voltage pulse for the IEE and the voltage pulse for the TPG was set at 70 μs so as to use the ions with the highest ion density in the ionization region (Figure S4). Fig. 7a displays the spectra of acetone dimer ions obtained at the GPW of 42.5 μs for different IEVs. As displayed, the peak height is raised from 165 pA to 395 pA as varying the IEV from 400 to 0 V, with signal-to-noise ratio (SNR, baseline noise level is 2 pA) raised by 240%. Unlike the peak height, the resolving power [1] (R = td/ fwhm) for the acetone dimer peak slightly goes down from 91 to 81 as varying the IEV from 400 to 0 V, reduced by 11%. Similar results were observed when DMMP of 425 pptv was introduced into the 63Ni source using acetone as dopant. As shown in Fig. 7b, with the IEV of 400 V and the GPW of 52.5 μs, DMMP produced a dimer peak of 8 pA (SNR = 4) at a drift time of 3.64 ms (K0 = 1.41 cm2V−1s−1). By decreasing the IEV from 400 to 0 V, the height of the DMMP dimer peak goes up from 8 to 27.5 pA, with SNR raised by 345%. Meanwhile, the R for the DMMP dimer peak goes down from 84 to 77, reduced by 8.3%. The limit of detection (LOD, at SNR = 3) for DMMP dimer peak was also measured at the IEV of 0 V and a LOD of 200 pptv was obtained (Figure S5). Clearly, the enhancement in the SNR should be attributed to the increased ion density right in front of the TPG. The slight reduction in the resolving power is thus assigned to the coulomb repulsion [28] which goes stronger as more ions are released into the drift region at the same GPW.
5.2. Ion enrichment factor To quantitatively measure the ion density change in the ionization region while ions moving towards the TPG at different IEVs, the spectra of acetone dimer ions as increasing the GPW from 0.045 to 0.21 ms were recorded for different IEVs. The peak area of acetone dimer ions in each spectrum was calculated and plotted as a function of the GPW in Fig. 6a. As can be seen in Fig. 6a and Table S1, for the same IEV, the peak area increases linearly with the applied GPW in the range experimented. For different IEVs, the linearity remains but the slopes, that actually represents the average ion density in front of the TPG, are different. Dividing the slope by the TIC of 2.18 nA obtained at the TPG fully open status, the ion enrichment factor is thus obtained for depicting the ratio of the ion density right in front of the TPG versus the ion density formed by the ion source. As shown in Fig. 6b, the ion enrichment factor varies as the IEV varies, like 1.80 at the IEV of 0 V, 0.93 at the IEV of 400 V and 0.65 at the IEV of 700 V. That indicates the ions generated from the ion source could be enriched by 180% or diluted by 65% while migrating to the ion shutter by simply adjusting the IEV. Using the intercept of each fitted line with the GPW axis in Fig. 6a, the time need for ions to go through the ion depletion zone [27] of the TPG (defined as the gate penetration time, GPT) was calculated and plotted against the IEV in Fig. 6b. As can be seen, the calculated GPT and the experimentally measured GPT show the same slightly decreasing trend as the IEV varying from 0 to 700 V. That should be attributed to the decreasing in the size of the TPG ion depletion zone, as indicated by the narrowing of the distance between M1 and M2 in the inset of Fig. 3. Notably, the calculated GPT values are always higher than the experimentally measured values. We speculate it is caused by the non-uniform ion density distribution in the ionization region close to the vicinity of the TPG, as being demonstrated by the leading edges of the ion current curves in Fig. 5. That also explains why the ion enrichment factor at the IEV of 400 V is 0.93, smaller than the value of 1
6. Conclusions With the development of the ion enrichment method, two main things were conducted in this work: the proving of the ion enrichment and ion dilution effects of the non-uniform electrostatic field and the performance demonstration of the ion enrichment method. For proving the ion enrichment and ion dilution effects, three prerequisite conditions must be satisfied: first, continuous flow of ions coming from the ion source is uniform; second, the electrostatic field in the ionization region goes back to the same homogeneous case at the TPG open status no matter how the electrostatic field is varied at the TPG closed status; and third, the ion transmission efficiency through the TPG is consistent during each TPG opening interval. To satisfy the above three conditions, a voltage pulse was designed and applied to the electrode in the ionization region which was adjacent to Grid 1 of the TPG, as shown in Fig. 4. With regard to the performance of the ion enrichment method, promising results were obtained, like the SNR of DMMP dimer peak was enhanced by 345% and the LOD for DMMP dimer peak was lowered from 425 to 200 pptv. In practical applications, there is no need to prove the ion
Fig. 6. (a) Peak area of acetone dimer ions as a function of the GPW for different IEVs. The slope of each linearly fitted line represents the average ion density in front of the TPG, while the intercept of each fitted line with the GPW axis represents the time need for ions to go through the ion depletion zone of the TPG (defined as the calculated gate penetration time, calculated GPT). (b) The ion enrichment factor as a function of the IEV, as well as the calculated GPT and the experimentally measured GPT. The ion enrichment factor is calculated as the slope of each fitted line in (a) divided by the TIC (2.18 nA) obtained when the TPG is fully open. The experimentally measured GPT is the minimum GPW for observing a acetone dimer signal with S/N = 3. Please refer to Table S1 for detailed information. 184
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Fig. 7. (a) Spectra of the acetone dimer ions obtained at the GPW of 42.5 μs for different IEVs; (b) Spectra obtained at the GPW of 52.5 μs for different IEVs when DMMP of 425 pptv was introduced into the 63Ni ion source using acetone as dopant.
enrichment or the ion dilution effect of non-uniform electrostatic field on a continuous flow of ions. The method proposed in this work could be employed by applying a constant gradually weakening electrostatic field in the ionization region to enrich ions during the whole ion shutter operating period, as shown in Figure S6. In that way, there is no need of an extra voltage pulse except the one for controlling the TPG ion shutter. Also, it is much easier to optimize the electrostatic field in the ionization region for obtaining better SNR gains. The ion enrichment method based on non-uniform electrostatic field needs no radial-confining RF voltage and it does not affect the response speed of the IMS device. The purpose of this work is to provide these understandings for helping researchers design high performance IMS devices. These understandings might also be useful in designing ion funnels or other ion transmission devices where an axial electrostatic field is needed.
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Conflict of interest statement The authors declare no competing financial interest. Acknowledgements This work was supported by the National Key R&D Program of China (Project No. 2016YFC0201200 and 2016YFC0800902), National Natural Science Foundation of China (Grant No. 21405158), Dalian Institute of Chemical Physics (Grand No. DICP ZZBS201709 and DICP ZZBS201801), Scientific Study Project of Liaoning Province Educational Commission of China (Grand No. LQ201715001), and CAS President's International Fellowship Initiative (Grand No. 2019VEA0033). The authors express their sincere appreciation to Dr. Glenn E. Spangler for discussing the experimental results. Dedicated to the 70th anniversary of Dalian Institute of Chemical Physics, CAS. Appendix A. Supplementary data Supplementary material related to this article can be found, in the online version, at doi:https://doi.org/10.1016/j.snb.2019.05.088. References [1] G.A. Eiceman, Z. Karpas, H.H. Hill, Ion Mobility Spectrometry, CRC Press, Boca Raton, FL, 2013. [2] M. Joshi, Ion mobility spectrometry in forensic science, Encyclop. Anal. Chem. (2017) 1–22. [3] J. Puton, J. Namieśnik, Ion mobility spectrometry: current status and application for chemical warfare agents detection, TrAC Trends Anal. Chem. 85 (2016) 10–20. [4] Md.M. Contreras, N. Jurado-Campos, C.S.-C. Callado, M. Arroyo-Manzanares, L. Fernandez, S. Casano, S. Marco, L. Arce, C. Ferreiro-Vera, Thermal desorption-ion mobility spectrometry: a rapid sensor for the detection of cannabinoids and discrimination of Cannabis sativa L. Chemotrypes, Sens. Actuators B: Chem. 237 (2018) 1413–1424. [5] R.M. O’Donnell, X. Sun, Pd.B. Harrington, Pharmaceutical applications of ion mobility spectrometry, TrAC Trends Anal. Chem. 27 (2008) 44–53.
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Enhancing the sensitivity of ion mobility spectrometry using the ion enrichment effect of non-uniform electrostatic field Chuang Chena, Hong Chena,b, Dandan Jianga, Mei Lia,b, Wei Huanga, Haiyang Lia,
T
⁎
a CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, People’s Republic of China b University of Chinese Academy of Sciences, Beijing, 100039, People’s Republic of China
A R T I C LE I N FO
A B S T R A C T
Keywords: Ion mobility spectrometry Sensitivity Non-uniform electrostatic field Ion enrichment SIMION simulation
The diversified applications of ion mobility spectrometry (IMS) frequently pose challenges to the sensitivity of IMS measurements. In this work, the ion density evolution profiles of a continuous flow of ions travelling in nonuniform electrostatic fields were studied. Based on that, an ion enrichment method was proposed for enhancing the sensitivity of IMS. It employed a gradually weakening electrostatic field in the ionization region of IMS and achieved ion density enhancement for the ion flow migrating from the ion source to the ion shutter. Using that method, the ion density of the ion flow produced by the ion source was increased by 180% when approaching the ion shutter. With the increased ion density, the limit of detection (LOD) for DMMP dimer peak was lowered from 425 to 200 pptv. Meanwhile, there was a slight reduction in the resolving power, which was tentatively assigned to the enhanced coulomb repulsion along with the increased ion density. The resolving power of the IMS with a drift length of 60 mm was still maintained around 80 at 100 degrees Celsius. The ion enrichment method needs no radial-confining radio frequency voltage. Also, it does not affect the response speed of IMS.
1. Introduction Ion mobility spectrometry (IMS) is a gas-phase ion separation and detection technique based on the ion mobility (K0) differences among ions in an electric field [1]. It plays a key role in security screening sensors targeting at explosives, narcotics and chemical warfare agents [2–4]. Much of that success is attributed to its satisfactory features: fast response, good portability, low cost and moderately high sensitivity at ambient pressure. Moreover, the capabilities of IMS to work at either ambient pressure or sub-ambient pressure and to combine with different ambient ion sources have opened avenues for applications in many other areas of analytical chemistry. As a standalone monitoring tool, IMS has been used for pharmaceutical [5], food [6], clinical [7] and environmental analyses [8]. When hyphenated to gas chromatography (GC) or mass spectrometry (MS), IMS offers an additional separation dimension to GC or MS and has been extensively used to characterize analytes in complex matrixes [9,10]. These diversified applications, however, frequently pose challenges to the sensitivity of IMS with direct sample introduction system, especially as the concentrations of target analytes go down to sub-ppbv or sub-ng levels. Sample preconcentration is widely used to improve the sensitivity of IMS measurements. Typical methods for pretreating samples before
⁎
introducing them to IMS include dispersive liquid-liquid microextraction (DLLME), solid-phase extraction (SPE), and solid-phase microextraction (SPME) [11]. Arce et al. [12] coupled a Tenax TA trap column to photoionization ion mobility spectrometer and achieved sensitive detection of BTEX present in gaseous samples. The limit of detection (LOD) for benzene and toluene was lowered to 0.54 and 0.57 mg/m3, respectively. Recently, these sample pretreatment methods begin to combine with various smart sorbents, such as immunosorbents, molecularly imprinted polymers, and nano-materials, and demonstrate very high efficiency in selective extraction and enrichment of target analytes from complex matrices [13]. As reported by Tabrizchi et al. [14], using Au-NPs-thiol silane film/SPME fiber coupled to corona discharge IMS, acetone of 1 pptv in human breath was measured. Sample preconcentration, however, usually takes a long time ranging from several minutes to tens of minutes, which might reduce the analysis throughput of IMS, especially for field screening IMS devices. IMS is typically a pulsed analytical technique. Improving its duty cycle could effectively enhance the ion signals of IMS for analysis of complex mixtures. One method to improve the duty cycle is temporal multiplexing, where the ion shutter of IMS is operated using multiple time-dispersive pulses within a single data acquisition cycle. Fourier
Corresponding author. E-mail address: [email protected] (H. Li).
https://doi.org/10.1016/j.snb.2019.05.088 Received 19 February 2019; Received in revised form 23 May 2019; Accepted 24 May 2019 Available online 25 May 2019 0925-4005/ © 2019 Elsevier B.V. All rights reserved.
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[15], Hadamard [16], and Cross-correlation [17] sequences have all been employed to generate an overlapped mobility spectrum and then retrieve a single time-dispersion spectrum via deconvolution. Using temporal multiplexing, the duty cycle of IMS could be increased up to 50%. As reported by Hill et al. [15], the enhanced duty cycle led to a signal-to-noise ratio (SNR) gain of around 10 comparing to conventional IMS. Not only the sensitivity, temporal multiplexing is also good for IMS to achieve high resolving power. Clowers et al. [17] used Crosscorrelation to obtain a SNR gain of 8 and meanwhile push the resolving power of IMS close to its theoretical value. However, temporal multiplexing in IMS usually requires stable ion source and sample introduction during the data acquisition circle for achieving better SNR gains. That is not practical for field screening IMS or online monitoring IMS devices. Besides, due the imperfect gating performance and the ion depletion effect of ion shutters in IMS, there always are false peaks resulting from modulation defects, which researchers are still trying to eliminate. Another method to improve the duty cycle of IMS is the use of an ion trap device before each IMS experiment to accumulate the ions produced by the ionization source while the last ion packet is separated in the drift region, then the stored ions are pulsed into the drift region of IMS for the next data acquisition cycle. Clemmer et al. [18] reported a method of using the ion funnel trap (IFT) in a cyclical drift tube IMS-MS experiment. The IFT was demonstrated to improve the duty cycle from 0.2% to 25%, allowing the observation of ions travelled over 100 cycles around the cyclotron where a resolving power in excess of 1000 was achieved for separating a mixture of peptides with similar mobilities. Recently, Smith et al. [19] reported a compression ratio ion mobility programming (CRIMP) approach to accumulate and compress ions for IMS-MS analysis. That enhanced the LOD for peptides and provided an 100-fold increase in sensitivity compared to their previous work using an IFT. However, these above designs usually require a working pressure of several millibar and a radial-confining RF voltage. They are not compatible with standalone or hyphenated IMS devices working at atmospheric pressure since ions cannot be effectively transferred across the high-pressure differential of the interface. Spatial ion packet compression based on electric field switching has also been used to improve the sensitivity of IMS measurements. It employs a high voltage pulse to enhance the electric field in a spatially confined region during the ion shutter opening period. Thereby, the packet of ions existing in that region would be compressed into the drift region of IMS and form a narrower ion packet with higher ion density. Finally, an ion peak with high signal to noise is observed. Using that method, an field switching (FS) ion shutter for efficient ion injection was developed by Jenkins [20] and Leonhardt et al. [21]. Gunzer et al. [22] used the FS ion shutter to efficiently pulse the ions generated by a non-radioactive electron source into the drift region of IMS. Kirk et al. [23] further used the FS ion shutter to develop a compact IMS possessing high sensitivity (reaching pptv level) and high resolving power (reaching 183). Besides, Li et al. [24] also combined the FS ion shutter with Bradbury-Nielsen gate (BNG) for injecting more ions into the drift region during the BNG opening interval. Even all these techniques target at spatially confined ion packets and involve electric field switching, the spatial ion packet compression is actually subject to the non-uniform electric field induced by the high voltage pulse. As Gunzer et al. [25] explained, for an ion packet moving in a gradually weakening electric field, its trailing edge moves faster than its leading edge, causing its spatial width reduced and ion density increased. The underlying principle of the spatial ion packet compression inspires us to further explore the ion density evolution of a continuous flow of ions in non-uniform electrostatic fields, especially the flow of ions drifting in the ionization region of IMS, which is important for designing IMS with high sensitivity. The aim of this work is to propose an ion enrichment method based on non-uniform electrostatic field for enhancing the sensitivity of IMS measurements. For that purpose, the influence of electrostatic field on the movement behavior of a
Fig. 1. Illustration of the spatial width and the ion density evolutions of ions travelling under different electrostatic fields.
continuous flow of ions was mathematically elucidated first, followed by a simulation validation using the SDS model of SIMION software. It was found that, ions from the ion source could be enriched or diluted while migrating towards the ion shutter by simply applying a gradually decreasing or enhancing electrostatic field along the ion drift direction in the ionization region of IMS, which was further experimentally proved. On that basis, the performance of the proposed method in improving the sensitivity of IMS was demonstrated. 2. Mathematical elucidation for ions travelling under electrostatic fields As displayed in Fig. 1, at timing start point t = 0, a packet of positive ions with a mobility K, an initial ion density n, and an initial spatial width δ is about to travel along the x direction in a positive electrostatic field E(x) (E/N < 2 Td, 1 Td = 10−17 V·cm2), resembling the field in the ionization region of the IMS. Considering the electric field as the only factor that influences the ion transport, the time difference for the trailing edge and the leading edge of the ions to arrive at x = d (d > δ) could be expressed as
Δti = ttrailing − tleading = =
∫0
d
dx − K ⋅E (x )
∫δ
d
δ K ⋅E (ξ )
dx = K ⋅E (x )
∫0
δ
dx K ⋅E (x ) (1)
where, ξ is a value on the x-axis which meets 0 < ξ < δ and the Lagrange’s Mean Value Theorem. Assume the leading edge of the ion packet keeps travelling under electric field E(d) after it arrives at x = d, when the trailing edge arrives, the spatial width δi and the ion density ni of the ion packet goes beyond x = d could be expressed as
δi = K ⋅E (d )⋅Δti = K ⋅E (d)
ni =
δ E (d ) = δ K ⋅E (ξ ) E (ξ )
E (ξ ) E (0) n⋅S⋅δ δ n≈ n = n= E (d ) E (d ) S⋅δi δi
(2)
(3)
where, S is the cross section of the ion packet perpendicular to the x direction. Making the initial width (δ) of the ion packet infinitely close to 0, the E(ξ) in Eq. (3) could be further approximately expressed as E (0). In fact, an infinite number of ion packets being generated successively in the time domain are actually a continuous flow of ions. Thus, Eq. (3) could also be used to depict the ion density evolution of a continous flow of ions travelling in E(x). Here, an ion enrichment factor ηn defined as ni divided by n is proposed to evaluate how the ion density 180
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would evolve for a continous flow of ions travelling in E(x), as show by Eq. (4).
ηn =
ni E (0) ≈ n E (d )
Grid 2 of the TPG while maintaining the potentials on all the other electrodes unchanged. Specifically, at the TPG open status, potentials of 2900, 2500, 2100, 1700, 1300, 900, 500, 400, and 0 V are applied to Plate 1, Ring 1, Ring 2, Ring 3, Ring 4, Ring 5, Grid 1, Grid 2, and Plate 2, forming an electric field along the x direction in the ionization and the drift regions. As the potential difference between Grid 1 and Grid 2 (defined as the gate penetration voltage, GPV) is 100 V, the x-component of the electric field Ex (Ex = -∂V/∂x) in the gate region is along the x direction (Ex > 0), allowing positive ions to go through the TPG. To closed the TPG, an extra voltage of 250 V (defined as the gate closing voltage, GCV) is superposed on the original potential (400 V) of Grid 2, while the potentials on all the other electrodes are maintained unchanged. The direction of the Ex in the gate region is reversed (Ex < 0), preventing positive ions from going through the TPG. Using the above IMS working mode, the movement behaviors of ions under the influence of the electric field in the ionization region during the TPG opening and closing interval was studied. At timing start point t =0 μs when the TPG is open, 5000 acetone dimer ions ((Ac)2H+ with SIMION estimated K0 of 2.3 cm2V−1s−1) randomly distributed in a cylindrical volume of 8 mm in diameter and 10 mm in length are generated at the top of the ionization region, as demonstrated by the green dots in Fig. 2a. Under the force of the electric field, the ions move with size unchanged till their leading edge approached the TPG, as demonstrated by the red dots in Fig. 2a. Similar phenomenon is observed when applying a GCV to close the TPG, as displayed by Fig. 2b. With the size unchanged, the ions move towards the TPG with no changing in the ion density. As closing the TPG, simultaneously changing the voltage difference between Ring 5 and Grid 1 (defined as the ion enrichment voltage, IEV) but maintaining the potential differences between any other two adjacent electrodes in the ionization region at 400 V, different size evolution profiles could be observed. As displayed by Fig. 2c, with the IEV varied to 100 V, the ions get compressed along the x direction as moving towards the TPG, forming a size smaller than their initial size. While, with the IEV varied to 700 V, the ions get elongated along the x direction as moving towards the TPG, forming a size bigger than their initial size, as displayed by Fig. 2d. A change in the size corresponds to a change in the ion density; the ions get enriched at the IEV of 100 V
(4)
Obviously, ηn is subject to the ratio of E(0) versus E(d). (1) If ∂E(x)/ ∂x = 0, then E(x) ≡ E(0) and ηn = 1, indicating the ion flow will keep its ion density in uniform electrostatic field no matter how distant it travels. (2) If ∂E(x)/∂x ≠ 0, then the ion packet travels in an non-uniform electrostatic field; There are three situations: (a) When E(0) < E (d), then ηn < 1, the ion flow is diluted; the smaller the value of ηn is, the lower the ion density gets. (b) When E(0) = E(d), ηn = 1, the ion flow would keep its ion density even in non-uniform electrostatic field. (c) When E(0) > E(d), ηn > 1, the ion flow is enriched; the bigger the value of ηn is, the higher the ion density gets. 3. SIMION simulation of ions drifting in the ionization region The movement behaviors of ions under the influence of different electrostatic fields in the ionization region of IMS were explored using the SDS model of SIMION software at 100 degrees Celsius. The repulsion between ions was not considered and the geometry of the IMS drift tube was simplified as described below. As displayed in Fig. 2a, two round electrodes with thickness of 0.94 mm and diameter of 30 mm, Plate 1 and Plate 2, are positioned in parallel at x = -1.00 mm and x = 36.06 mm, confining a space resembling the IMS drift tube. A Tyndall-Powell gate (TPG) comprised of two 0.06 mm-thick grids, Grid 1 and Grid 2, is placed between the two round electrodes, separating the space into three regions: the ionization, the gate, and the drift regions. The grids are positioned in parallel at x = 29.94 mm and x = 31.00 mm, keeping a grid-to-grid distance of 1 mm. The two grids are identical wire grids, having parallel square wires with side length of 0.06 mm and a wire-to-wire distance of 0.60 mm, as used in the following experiments. Five annular electrodes, Rings 1–5, are co-axially placed in the ionization region, cutting it in to six even zones. The rings are of 0.06 mm thick, having an inner diameter of 15 mm and an outer diameter of 30 mm. The IMS usually works with a periodical voltage pulse applied to
Fig. 2. Movement behaviors of acetone dimer ions in the ionization region of the IMS at 100 degrees Celsius. (a) The Tyndall-Powell gate (TPG) is open. In the ionization region, the potential differences between any two adjacent electrodes are maintained at 400 V. (b) The TPG is closed. Only an extra voltage of 250 V (defined as the gate closing voltage, GCV) is superposed on the original potential (400 V) of Grid 2 for closing the TPG, the potentials on all the other electrodes are maintained. (c) The TPG is closed. As closing the TPG, the potential difference between Ring 5 and Grid 1 (defined as the ion enrichment voltage, IEV) is reduced to 100 V, but the potential differences between any other two adjacent electrodes in the ionization region are maintained at 400 V. (d) The TPG is closed. As closing the TPG, the IEV is increased to 700 V, but the potential differences between any other two adjacent electrodes in the ionization region are maintained at 400 V. For each case, the distribution profiles of the ions at the timing start point t = 0 μs (green dots) and when its leading edge approached the TPG (red dots) are recorded. All the black rectangles are of the same size (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article). 181
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Fig. 3. Ex versus x plot along the axis of the IMS drift tube (y = 0 mm) at the TPG open status and Ex versus x plots along y = 0 mm at the TPG closed status with varying the IEV from 0 to 700 V. The GPV stands for the gate penetration voltage defined as the voltage difference between Grid 1 and Grid 2 at the TPG open status, while the GCV stands for the gate closing voltage defined as the extra voltage superposed on the original potential (400 V) of Grid 2 for closing the TPG.
Fig. 4. Schematic of the Tyndall-Powell gate (TPG) ion mobility spectrometer (top) and the voltage controlling scheme (bottom) for studying the effect of non-uniform electrostatic field on ions drifting in the ionization region. The IEE stands for the ion enrichment electrode. The voltage pulse for Grid 2 is for controlling the TPG to open for an interval (GPW) in every 30 ms. The voltage pulse for IEE, having a period of 30 ms and a duty cycle of 50%, is for maintaining the potential difference between IEE and Grid 1 at 400 V when the TPG is open and changing the potential difference between IEE and Grid 1 (defined as the ion enrichment voltage, IEV) to a value of 0–700 V when the TPG is closed. Note, the delay time (dt) between the two pulses is normally set at 0 μs without specific notification.
up from 80 V/mm to a plateau along the x direction; the bigger the IEV is, the higher the plateau is. Oppositely, decreasing the IEV to be smaller than 400 V, the Ex value gradually goes down from 80 V/mm to a valley along the x direction; the smaller the IEV is, the deeper the valley is. Similar phenomena could be observed for some other y lines, as displayed in Figure S1. At ambient pressure, the ion drift velocity is proportional to the electrostatic field (E/N < 2 Td) [1]. In an uniform field, the ions of the same K0 in the ionization region possess the same drift velocity, ensuring them to move towards the TPG with no changing in the ion density distribution profile. While, in a gradually weakening or strengthening electric field, the ions of the same K0 at different locations of the ionization region possess different drift velocities; some ions
and diluted at the IEV of 700 V while drifting towards the TPG. To explain the movement behaviors of the ions in the ionization region as discussed above, the Ex values inside the IMS drift tube at the TPG open status and at the TPG closed status with varying the IEV from 0 to 700 V were recorded. Fig. 3 displays the evolution profiles of the Ex versus x plot along the axis of the IMS drift tube (y = 0 mm) at the TPG open and closed statuses. Clearly, at the TPG open status, the Ex versus x plot has uniform Ex values of 80 V/mm in the ionization region, as shown by the black plot in Fig. 3. However, at the TPG closed status, the IEV value markedly affects the Ex distribution profile in the ionization region. With the IEV maintained at 400 V, the Ex values in the whole ionization region keep nearly intact, as shown by the red plot in Fig. 3. Increasing the IEV to be higher than 400 V, the Ex value gradually goes 182
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collected by the faraday cup was amplified via a two-stage pre-amplifier with a gain of 109 V/A and a bandwidth of 41 kHz. The output of the pre-amplifier was fed to an oscilloscope (Tektronix, 2024C, U.S.) for spectra recording. Each recorded spectrum was the average of sixteen original spectra. Compressed air purified by activated carbon, silica gel, and fresh molecular sieves was fed into a pneumatic system to generate drift, dopant, and sample gases at flow rate of 100, 5, and 5 mL·min−1, respectively, as represented in Figure S2. The humidity of the purified air was below 1 ppmv. The gases were all preheated to 100 degrees Celsius before entering the drift tube. Acetone and DMMP (dimethylmethylphosphonate) of analytical grade were used as dopant and analyte, respectively. They both were introduced into the pneumatic system via online permeation and purging. The acetone dopant gas with a concentration above 20 ppmv was used to react with most of the reactant ions in the 63Ni source and form a single product ion peak. The DMMP sample gas at different concentrations generated via online dilution was used to test the sensitivity of the IMS. For safety consideration, active carbon traps were used to capture acetone and DMMP from the gas outlets of the IMS and the pneumatic system to prevent environmental pollution. All the power supplies were operated only by trained personnel.
move fast and some ions move slow, forcing them to aggregate or segregate while moving towards the TPG. And, the stronger the weakening or the strengthening is, the more prominent the aggregation or the segregation would become. This matches the prediction of the mathematical model proposed above. The movement behaviors of the ions displayed in Fig. 2 could thus be explained. Based on the above understandings, in practical IMS, by applying heterogeneous electrostatic fields in the ionization region during the TPG closed interval and switching them back to exactly the same uniform field during the TPG open interval, there is possibility to explore the effect of non-uniform electrostatic field on the ion density evolution of a continuous flow of ions. To do that, it is necessary to have an ion source which generates constant flow of ions. 4. Experimental section The Tyndall-Powell gate (TPG) ion mobility spectrometer used in this work was constructed at our laboratory, as schematically displayed in Fig. 4 (top). The IMS cell comprised a faraday cup, a drift region of 60 mm long, a TPG, an ionization region of 30 mm long, and a 10 mCi cylindrical 63Ni source. The drift region and the ionization region were both confined by alternatively stacked stainless steel rings (each 0.06 mm thick) and teflon rings (each 4.94 mm) with an outer diameter of 30 mm. The inner diameters of the drift region and the ionization region were 24 mm and 15 mm, respectively. The TPG comprised two identical wire grids of 0.06 mm thick separated by a teflon ring of 1 mm thick. The grids were made of stainless steel, having parallel square wires with side length of 0.06 mm and wire-to-wire distance of 0.6 mm. The wires spanned a hole of 15 mm in diameter on a disc of 30 mm in diameter. The ion source was placed between a round electrode and a wire grid the same as the one used for making the TPG. A high voltage power supply (HV0) and a resistor chain were used to fix the potential of Grid 1 at 5300 V (V1) and the potential of Grid 2 at 5200 V (V0) while the TPG was open, meanwhile forming an uniform potential difference of 400 V for any adjacent electrodes in the drift region. The potential difference, V1 - V0, was defined as the gate penetration voltage (GPV) and the GPV was fixed at 100 V. A first isolated high voltage power supply (IHV1) with an output of 250 V floating on the potential V0 and a first high voltage pulse generator (DEI, PVX4110, U.S.) were used to produce a voltage pulse for Grid 2, as shown by the red voltage wave in Fig. 4 (bottom). The voltage pulse for Grid 2 periodically varied between V0 and V2 so as to control the TPG to open for an interval (gate opening pulse width, GPW) every 30 ms. The potential difference, V2 - V0, was defined as the gate closing voltage (GCV) and the GCV was fixed at 250 V. A second isolated high voltage power supply (IHV2) with an fixed output of 400 V floating on the potential V1, a third isolated high voltage power supply (IHV3) with an adjustable output of 0–700 V floating on the potential V1, and a second high voltage pulse generator (DEI, PVX-4110, U.S.) were used to produce a voltage pulse for the electrode in the ionization region which was adjacent to Grid 1 (named as the ion enrichment electrode, IEE), as shown by the blue voltage wave in Fig. 4 (bottom). The voltage pulse for IEE, having a period of 30 ms and a duty cycle of 50%, was for maintaining the potential difference between IEE and Grid 1 at 400 V when the TPG was open and changing the potential difference between IEE and Grid 1 (defined as the ion enrichment voltage, IEV) to a value of 0–700 V when the TPG was closed. The voltage pulse for IEE and the voltage pulse for Grid 2 were normally synchronized. Their rising and falling edges were all less than 100 ns. Specifically, a delay time (dt) between them, as shown in Fig. 4 (bottom), could also be set for screening the ion density distribution profiles in the ionization region. A fourth isolated high voltage power supply (IHV4) with an output of 2400 V floating on the potential of IEE was used to form an uniform potential difference of 400 V for all the other adjacent electrodes in the ionization region, no matter the TPG was open or closed. The IMS cell was kept at 100 degrees Celsius. The ion current
5. Results and discussion 5.1. Ion enrichment and ion dilution effects To see how the IEV affects the movement behavior of ions in the ionization region, the spectra of acetone dimer ions at the GPW of 6 ms were obtained as varying the IEV from 0 to 700 V. As displayed in Fig. 5, with the IEV varying from 0 to 700 V, the trailing edges of all the ion current curves superpose well, while the leading edges show very different height changing patterns. At the IEV of 400 V, the ion current curve shows a nearly square leading edge, which quickly reaches the flat TIC level. Decreasing the IEV to be lower than 400 V, the leading edge firstly shoots up to be higher than the TIC level and then gradually goes down to the TIC level; and, the lower the IEV is, the higher the leading edge is. On the contrary, increasing the IEV to be higher than 400 V, the leading edge firstly shoots up to be lower than the TIC level and then gradually goes up to the TIC level; and, the higher the IEV is, the lower the leading edge is. Siems et al. [26] pointed out that the leading edge of an ion bundle moving in the drift region remains the ion distribution features in the ionization region adjacent to the ion shutter. As the experimentally measured ion current is proportional to the ion density, the leading edge of the ion current curve shown in Fig. 5 exactly reflects the ion
Fig. 5. Spectra of acetone dimer ions obtained at a GPW of 6 ms with the IEV varying from 0 to 700 V. The TIC stands for the total ion current obtained with the 63Ni ion source using acetone as dopant at the TPG fully open mode. 183
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for the ideal uniform distribution case.
density distribution profile in the ionization region adjacent to the TPG. At the IEV of 400 V, the ions in the whole ionization region share nearly the same ion density. While, as the IEV deviating from 400 V, the ions in the ionization region begins to possess a gradually increasing (IEV < 400 V) or decreasing (IEV > 400 V) ion density along the ion drift direction; And, the more the deviation is, the more the increment or the decrement is. That phenomenon is named as the ion enrichment and ion dilution effects. Considering the facts that varying the IEV at the TPG closed status does not affect the electric field in the vicinity of the 63Ni ion source (see Fig. 3) and the rising or falling edge of the voltage pulse on IEE does not affect the movement of ions in the ionization region (see Figure S3), the ion enrichment and ion dilution effects are mainly achieved by the IEV induced non-uniform electrostatic field in the ionization region during the TPG closing period, as discussed in the SIMION simulation section.
5.3. Sensitivity and resolving power To explore the influence of the ion enrichment effect on the sensitivity and the resolving power of the IMS, the delay time between the voltage pulse for the IEE and the voltage pulse for the TPG was set at 70 μs so as to use the ions with the highest ion density in the ionization region (Figure S4). Fig. 7a displays the spectra of acetone dimer ions obtained at the GPW of 42.5 μs for different IEVs. As displayed, the peak height is raised from 165 pA to 395 pA as varying the IEV from 400 to 0 V, with signal-to-noise ratio (SNR, baseline noise level is 2 pA) raised by 240%. Unlike the peak height, the resolving power [1] (R = td/ fwhm) for the acetone dimer peak slightly goes down from 91 to 81 as varying the IEV from 400 to 0 V, reduced by 11%. Similar results were observed when DMMP of 425 pptv was introduced into the 63Ni source using acetone as dopant. As shown in Fig. 7b, with the IEV of 400 V and the GPW of 52.5 μs, DMMP produced a dimer peak of 8 pA (SNR = 4) at a drift time of 3.64 ms (K0 = 1.41 cm2V−1s−1). By decreasing the IEV from 400 to 0 V, the height of the DMMP dimer peak goes up from 8 to 27.5 pA, with SNR raised by 345%. Meanwhile, the R for the DMMP dimer peak goes down from 84 to 77, reduced by 8.3%. The limit of detection (LOD, at SNR = 3) for DMMP dimer peak was also measured at the IEV of 0 V and a LOD of 200 pptv was obtained (Figure S5). Clearly, the enhancement in the SNR should be attributed to the increased ion density right in front of the TPG. The slight reduction in the resolving power is thus assigned to the coulomb repulsion [28] which goes stronger as more ions are released into the drift region at the same GPW.
5.2. Ion enrichment factor To quantitatively measure the ion density change in the ionization region while ions moving towards the TPG at different IEVs, the spectra of acetone dimer ions as increasing the GPW from 0.045 to 0.21 ms were recorded for different IEVs. The peak area of acetone dimer ions in each spectrum was calculated and plotted as a function of the GPW in Fig. 6a. As can be seen in Fig. 6a and Table S1, for the same IEV, the peak area increases linearly with the applied GPW in the range experimented. For different IEVs, the linearity remains but the slopes, that actually represents the average ion density in front of the TPG, are different. Dividing the slope by the TIC of 2.18 nA obtained at the TPG fully open status, the ion enrichment factor is thus obtained for depicting the ratio of the ion density right in front of the TPG versus the ion density formed by the ion source. As shown in Fig. 6b, the ion enrichment factor varies as the IEV varies, like 1.80 at the IEV of 0 V, 0.93 at the IEV of 400 V and 0.65 at the IEV of 700 V. That indicates the ions generated from the ion source could be enriched by 180% or diluted by 65% while migrating to the ion shutter by simply adjusting the IEV. Using the intercept of each fitted line with the GPW axis in Fig. 6a, the time need for ions to go through the ion depletion zone [27] of the TPG (defined as the gate penetration time, GPT) was calculated and plotted against the IEV in Fig. 6b. As can be seen, the calculated GPT and the experimentally measured GPT show the same slightly decreasing trend as the IEV varying from 0 to 700 V. That should be attributed to the decreasing in the size of the TPG ion depletion zone, as indicated by the narrowing of the distance between M1 and M2 in the inset of Fig. 3. Notably, the calculated GPT values are always higher than the experimentally measured values. We speculate it is caused by the non-uniform ion density distribution in the ionization region close to the vicinity of the TPG, as being demonstrated by the leading edges of the ion current curves in Fig. 5. That also explains why the ion enrichment factor at the IEV of 400 V is 0.93, smaller than the value of 1
6. Conclusions With the development of the ion enrichment method, two main things were conducted in this work: the proving of the ion enrichment and ion dilution effects of the non-uniform electrostatic field and the performance demonstration of the ion enrichment method. For proving the ion enrichment and ion dilution effects, three prerequisite conditions must be satisfied: first, continuous flow of ions coming from the ion source is uniform; second, the electrostatic field in the ionization region goes back to the same homogeneous case at the TPG open status no matter how the electrostatic field is varied at the TPG closed status; and third, the ion transmission efficiency through the TPG is consistent during each TPG opening interval. To satisfy the above three conditions, a voltage pulse was designed and applied to the electrode in the ionization region which was adjacent to Grid 1 of the TPG, as shown in Fig. 4. With regard to the performance of the ion enrichment method, promising results were obtained, like the SNR of DMMP dimer peak was enhanced by 345% and the LOD for DMMP dimer peak was lowered from 425 to 200 pptv. In practical applications, there is no need to prove the ion
Fig. 6. (a) Peak area of acetone dimer ions as a function of the GPW for different IEVs. The slope of each linearly fitted line represents the average ion density in front of the TPG, while the intercept of each fitted line with the GPW axis represents the time need for ions to go through the ion depletion zone of the TPG (defined as the calculated gate penetration time, calculated GPT). (b) The ion enrichment factor as a function of the IEV, as well as the calculated GPT and the experimentally measured GPT. The ion enrichment factor is calculated as the slope of each fitted line in (a) divided by the TIC (2.18 nA) obtained when the TPG is fully open. The experimentally measured GPT is the minimum GPW for observing a acetone dimer signal with S/N = 3. Please refer to Table S1 for detailed information. 184
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Fig. 7. (a) Spectra of the acetone dimer ions obtained at the GPW of 42.5 μs for different IEVs; (b) Spectra obtained at the GPW of 52.5 μs for different IEVs when DMMP of 425 pptv was introduced into the 63Ni ion source using acetone as dopant.
enrichment or the ion dilution effect of non-uniform electrostatic field on a continuous flow of ions. The method proposed in this work could be employed by applying a constant gradually weakening electrostatic field in the ionization region to enrich ions during the whole ion shutter operating period, as shown in Figure S6. In that way, there is no need of an extra voltage pulse except the one for controlling the TPG ion shutter. Also, it is much easier to optimize the electrostatic field in the ionization region for obtaining better SNR gains. The ion enrichment method based on non-uniform electrostatic field needs no radial-confining RF voltage and it does not affect the response speed of the IMS device. The purpose of this work is to provide these understandings for helping researchers design high performance IMS devices. These understandings might also be useful in designing ion funnels or other ion transmission devices where an axial electrostatic field is needed.
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Conflict of interest statement The authors declare no competing financial interest. Acknowledgements This work was supported by the National Key R&D Program of China (Project No. 2016YFC0201200 and 2016YFC0800902), National Natural Science Foundation of China (Grant No. 21405158), Dalian Institute of Chemical Physics (Grand No. DICP ZZBS201709 and DICP ZZBS201801), Scientific Study Project of Liaoning Province Educational Commission of China (Grand No. LQ201715001), and CAS President's International Fellowship Initiative (Grand No. 2019VEA0033). The authors express their sincere appreciation to Dr. Glenn E. Spangler for discussing the experimental results. Dedicated to the 70th anniversary of Dalian Institute of Chemical Physics, CAS. Appendix A. Supplementary data Supplementary material related to this article can be found, in the online version, at doi:https://doi.org/10.1016/j.snb.2019.05.088. References [1] G.A. Eiceman, Z. Karpas, H.H. Hill, Ion Mobility Spectrometry, CRC Press, Boca Raton, FL, 2013. [2] M. Joshi, Ion mobility spectrometry in forensic science, Encyclop. Anal. Chem. (2017) 1–22. [3] J. Puton, J. Namieśnik, Ion mobility spectrometry: current status and application for chemical warfare agents detection, TrAC Trends Anal. Chem. 85 (2016) 10–20. [4] Md.M. Contreras, N. Jurado-Campos, C.S.-C. Callado, M. Arroyo-Manzanares, L. Fernandez, S. Casano, S. Marco, L. Arce, C. Ferreiro-Vera, Thermal desorption-ion mobility spectrometry: a rapid sensor for the detection of cannabinoids and discrimination of Cannabis sativa L. Chemotrypes, Sens. Actuators B: Chem. 237 (2018) 1413–1424. [5] R.M. O’Donnell, X. Sun, Pd.B. Harrington, Pharmaceutical applications of ion mobility spectrometry, TrAC Trends Anal. Chem. 27 (2008) 44–53.
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