Highly Efficient Ion Manipulator for Tandem Ion Mobility Spectrometry: Exploring a Versatile Technique by a Study of Primary Alcohols.

In this work, we present a tandem ion mobility spectrometer (IMS) utilizing a highly efficient ion manipulator allowing to store, manipulate, and analyze ions under high electric field strengths and controlled ion-neutral reactions at ambient conditions. The arrangement of tandem drift regions and an ion manipulator in a single drift tube allows a sequence of mobility selection of precursor ions, followed by storage and analysis, mobility separation, and detection of the resulting product ions. In this article, we present a journey exploring the capabilities of the present instrument by a study of eight different primary alcohols characterized at reduced electric field strengths E/N of up to 120 Td with a water vapor concentration ranging from 40 to 540 ppb. Under these conditions, protonated alcohol monomers up to a carbon number of nine could be dissociated, resulting in 18 different fragmented product ions in total. The fragmentation patterns revealed regularities, which can be used for assignment to the chemical class and improved classification of unknown substances. Furthermore, both the time spent in high electrical field strengths and the reaction time with water vapor can be tuned precisely, allowing the fragment distribution to be influenced. Thus, further information regarding the relations of the product ions can be gathered in a standalone drift tube IMS for the first time.

Ultra-Fast Ion Mobility Spectrometer for High-Throughput Chromatography.

Fast chromatography systems especially developed for high sample throughput applications require sensitive detectors with a high repetition rate. These high throughput techniques, including various chip-based microfluidic designs, often benefit from detectors providing subsequent separation in another dimension, such as mass spectrometry or ion mobility spectrometry (IMS), giving additional information about the analytes or monitoring reaction kinetics. However, subsequent separation is required at a high repetition rate. Here, we therefore present an ultra-fast drift tube IMS operating at ambient pressure. Short drift times while maintaining high resolving power are reached by several key instrumental design features: short length of the drift tube, resistor network of the drift tube, tristate ion shutter, and improved data acquisition electronics. With these design improvements, even slow ions with a reduced mobility of just 0.94 cm2/(V s) have a drift time below 1.6 ms. Such short drift times allow for a significantly increased repetition rate of 600 Hz compared with previously reported values. To further reduce drift times and thus increase the repetition rate, helium can be used as the drift gas, which allows repetition rates of up to 2 kHz. Finally, these significant improvements enable IMS to be used as a detector following ultra-fast separation including chip-based chromatographic systems or droplet microfluidic applications requiring high repetition rates.

The origin of isomerization of aniline revealed by high kinetic energy ion mobility spectrometry (HiKE-IMS).

Although aniline is a relatively simple small molecule, the origin of its two peaks observed in ion mobility spectrometry (IMS) has remained under debate for at least 30 years. First hypothesized as a difference in protonation site (amine vs. benzene ring), each ion mobility peak differs by one Dalton when coupled with mass spectrometry where the faster mobility peak is the molecular ion peak, and the slower mobility peak is protonated. To complicate the deconvolution of structures, some previous literature shows the peaks as unresolved and thus proposes these species exist in equilibrium. In this work, we show that when measured with high kinetic energy ion mobility spectrometry (HiKE-IMS), the two peaks observed in spectra of both aniline and all n-fluoroanilines are fully separated (chromatographic resolution from 2-7, Rp > 110) and therefore not in equilibrium. The HiKE-IMS is capable of changing ionization conditions independently of drift region conditions, and our results agree with previous literature showing that ionization source settings (including possible fragmentation at this stage) are the only influence determining the speciation of the two aniline peaks. Finally, when the drift and reactant gas are changed to nitrogen, a third peak appears at high E/N for 2-fluoroaniline and 4-fluoroaniline for the first time in reported literature. As observed by HiKE-IMS-MS, the new third peak is also protonated showing that the para-protonated aniline and resulting fragment ion, molecular ion aniline, can be fully separated in the mobility domain for the first time. The appearance of the third peak is only possible due to the increased separation of the other two peaks within the HiKE-IMS.

Ultrasensitive Ion Source for Drift Tube Ion Mobility Spectrometers Combining Optimized Sample Gas Flow with Both Chemical Ionization and Direct Ionization.

Efficient ionization of analyte molecules is a crucial step for the outstanding sensitivity of ion mobility spectrometers (IMS) used for trace gas detection. Here, we present a new ion source that combines the previously published extended field switching ion shutter with two switchable ionization sources and an optimized sample gas flow that leads to a focused laminar stream through the reaction region of the ion source. The X-ray ionization source allows for chemical gas phase ionization of analyte molecules, while the UV ionization source allows for direct ionization of analyte molecules. The optimized sample gas flow not only allows for quickly washing out analyte molecules from the reaction region but also has improved sensitivity by a factor of about 5 for protonated monomers, 20 for proton-bound dimers, and over 100 for the proton-bound trimer of 1-octanol. The resulting limits of detection using chemical X-ray ionization are in the subpptv-range for protonated monomers and in the low pptv-range for proton-bound dimers, while the limits of detection using direct UV ionization are in the subppbv-range. Especially, a direct comparison between chemical and direct ionization of ketones using this ultrasensitive ion source reveals a stepwise conversion from directly ionized monomers to proton-bound dimers via protonated monomers during direct UV ionization.

Miniaturized Drift Tube Ion Mobility Spectrometer with Ultra-Fast Polarity Switching.

Ion mobility spectrometers (IMS) are well suited for detecting trace gases down to levels at ppbv and even pptv within 1 s of analysis time when using chemical ionization. The measuring principle is based on the separation and detection of the ionized constituents of a sample. Depending on the sample composition, certain ionization sources create both positive and negative analyte ions, but the simultaneous detection of both ion polarities usually requires two drift tubes. Contained within this effort, we present an alternative approach for detecting both ion polarities using one single drift tube that can switch the polarity of the drift tube within 12 ms. This technique allows for generating one positive and one negative ion mobility spectrum, each with a drift time range of 13 ms (minimum reduced ion mobility of K0 = 0.72 cm2 V-1 s-1), within a total experiment time of 50 ms. Additionally, ions are continuously generated in the ionization region during both the polarity switching and the analysis of one of the polarities, which allows for an effective ionization/reaction time of 25 ms. Comparable to the performance of similar instrument designs we reported previously, the presented device has a high resolving power of RP = 70 with a drift length of 51 mm. The limits of detection are for the monomers between 70 and 370 pptv and for the dimers between 450 and 800 pptv for 1 s of averaging for various ketones, methyl salicylate, and chlorinated hydrocarbons. Although this work focuses on applying ultra-fast polarity switching to an existing IMS, the techniques shown here may be applied to other IMS implementations for different applications.

Toward Compact High-Performance Ion Mobility Spectrometers: Ion Gating in Ion Mobility Spectrometry.

Printed circuit board (PCB) based drift tube ion mobility spectrometers enable the use of state-of-the-art production techniques to manufacture compact devices with excellent performance at minimum cost. The new PCB ion mobility spectrometer (PCB-IMS) presented here is equipped with either a 140 MBq tritium or a 95 MBq nickel-63 ionization source and consists of a combination of horizontally arranged 6-layer PCBs for the drift and reaction regions and vertically arranged PCBs for interfacing the ionization source, ion shutter, and detector. The design allows the reproducible manufacturing and thus comparison of different IMS topologies. Here, we investigate different ion shutters, field-switching, Bradbury-Nielsen, and tristate and their effects on resolving power and limits of detection considering two different ionization region geometries and ionization sources, tritium and nickel-63. It is shown that the high resolving power of RP > 80 at low drift voltage of 3 kV and short drift length of 50 mm can be achieved independent of the used ion shutter mechanism and reaction region geometry. While the resolving power of all ion shutters is excellent, the Bradbury-Nielsen shutter shows a pronounced discrimination of slow ion species when using short shutter opening times for small initial ion cloud widths, as required for high resolving power. Thus, the intensity of the proton-bound dimer of 2-pentanone is reduced by 30% compared to the signal intensity obtained with both the field-switching and tristate shutter. The detection limits employing the Bradbury-Nielsen shutter and a 50 mm reaction region as required for nickel-63 are 58 pptv for the protonated monomer and 3.4 ppbv for the proton-bound dimer of 2-pentanone. The detection limits achieved with the tristate shutter utilizing the same reaction region are slightly higher for the protonated monomer at 68 pptv, but lower for the proton-bound dimer at 2 ppbv due to the advanced ion shutter principle not discriminating slow ions. However, the lowest detection limits of 13 pptv and 301 pptv can be achieved with the field-switching shutter and a 2 mm reaction region, sufficient for a tritium ionization source.

Plate-height model of ion mobility-mass spectrometry: Part 2-Peak-to-peak resolution and peak capacity.

In a previous work, we explored zone broadening and the achievable plate numbers in linear drift tube ion mobility-mass spectrometry through developing a plate-height model [1]. On the basis of these findings, the present theoretical study extends the model by exploring peak-to-peak resolution and peak capacity in ion mobility separations. The first part provides a critical overview of chromatography-influenced resolution equations, including refinement of existing formulae. Furthermore, we present exact resolution equations for drift tube ion mobility spectrometry based on first principles. Upon implementing simple modifications, these exact formulae could be readily extended to traveling wave ion mobility separations and to cases when ion mobility spectrometry is coupled to mass spectrometry. The second part focuses on peak capacity. The well-known assumptions of constant plate number and constant peak width form the basis of existing approximate solutions. To overcome their limitations, an exact peak capacity equation is derived for drift tube ion mobility spectrometry. This exact solution is rooted in a suitable physical model of peak broadening, accounting for the finite injection pulse and subsequent diffusional spreading. By borrowing concepts from the theoretical toolbox of chromatography, we believe that the present study will help in integrating ion mobility spectrometry into the unified language of separation science.

Improving Ion Mobility Spectrometer Sensitivity through the Extended Field Switching Ion Shutter.

Field switching ion shutters allow generating short ion packets with high ion densities by first ionizing for several milliseconds in a field-free ionization region and then quickly pushing the entire ion population out into the drift region. Thus, they are an excellent choice for compact ion mobility spectrometers with both high resolving power and low limits of detection. Here, we present an improved setup, named the extended field switching ion shutter. By generating a second field-free region between the ionization region and the drift region, shielding of the ionization region is significantly improved, even when using grids with higher optical transparency to improve ion transmission into the drift region. Furthermore, it is shown that under certain conditions, ion transmission through multiple grids in series can even surpass transmission through a single grid of the same transparency. For the studied ions, the signal intensity at low concentrations increases by approximately a factor of 7 to 9 for protonated monomers, 10 to 14 for proton-bound dimers, and 25 for the proton-bound 1-octanol trimer compared to the classical field switching shutter. However, due to the nonlinear response for ions containing multiple analyte molecules, the limits of detection improve only by a factor of 3 to 4 for proton-bound dimers and 3 for the proton-bound 1-octanol trimer. Nevertheless, this still leads to single-digit pptv limits of detection for protonated monomers and hundred pptv limits of detection for proton-bound dimers measured for a series of ketones. However, for the most intense peaks such as the reactant ion peak, a significant loss of resolving power by a factor of up to 1.4 was observed due to Coulomb repulsion.

Compact and Sensitive Dual Drift Tube Ion Mobility Spectrometer with a New Dual Field Switching Ion Shutter for Simultaneous Detection of Both Ion Polarities.

Ion mobility spectrometers (IMS) with field switching ion shutters are an excellent choice for trace gas detection, being extremely sensitive while having fast response times. However, as different target molecules may form positive, negative, or even ions of both polarities, it is beneficial to simultaneously detect both ion polarities. Here, we present a dual drift tube IMS with a new dual field switching ion shutter for gating both ion polarities and an X-ray ionization source in orthogonal configuration. The dual field switching ion shutter allows significantly improved ion gating and ion accumulation due to improved shielding of the ionization region from the drift field. Equipped with two 75 mm long high-performance drift tubes, the dual IMS reaches high resolving power of R = 90 with detection limits in the lower pptv range for different ketones, chlorinated hydrocarbons and methyl salicylate that forms ions in both polarities.

Enhanced Resolving Power by Moving Field Ion Mobility Spectrometry.

Ion mobility spectrometry is a powerful detection method widely used in various applications. Particularly in field applications, ion mobility spectrometers (IMSs) are useful because of their extremely low detection limits at short measuring periods and their compact and robust design. However, especially small IMSs suffer from the consequences of low resolving power when compared to laboratory systems. Therefore, in this paper, we present a new approach to increase the resolving power of a drift time IMS without employing higher drift voltages and bulky power supplies. The so-called moving field IMS (MOF-IMS) presented here allows a more effective use of the available voltage because of a segmented drift region where only a small part is supplied with voltage. Even with the basic version of an MOF-IMS presented here, it was possible to increase the resolving power by 60% from 60 to 95 without increasing the required drift voltage.

Plate-height model of ion mobility-mass spectrometry.

In the past decade, ion mobility spectrometry (IMS) in combination with mass spectrometry (IM-MS) became a widely employed technique for the separation and structural characterization of ionic species in the gas phase. Similarly to chromatography, where studies on the mechanism of band broadening and adequate plate-height equations have been aiding method development and promoting advancements in column technology, a suitable resolving power theory of drift tube ion mobility-mass spectrometry (DTIM-MS) is essential to stimulate further progress in this emerging field of separation science. In the present study, therefore, we explore dispersion processes in detail and present a plate-height model of ion mobility-mass spectrometry. We quantify the effects of five major dispersion processes that contribute to zone broadening and determine the resolving power in DTIM-MS: diffusion, Coulomb repulsion, electric field inhomogeneities, the finite initial spread of the ion cloud and dispersion outside the mobility cell. A solution is provided to account for the nonuniform separation field in IM-MS in the presence of multiple compartments. The equations - derived from first principles - serve as the basis for formulating an expression that is similar in nature to van Deemter's plate-height equation for chromatography. A comprehensive set of experiments was performed on a custom-built DTIM-MS instrument to evaluate the accuracy of the plate-height model, resulting in satisfactory agreement between experiment and theory. Building on these findings, the plate-height equation was employed to explore the influence of drift gas pressure, injection pulse-width and the mobility of ions on resolving power from a theoretical point of view. Our findings may aid instrument design and development in the future, as well as the optimization of measurement conditions to improve ion mobility separations. By employing the plate-height concept and the general formalism of differential migration processes to describe zone spreading in IM-MS, we aim to find a common ground between this emerging method and such well-established techniques as HPLC or CZE. We also hope that the work presented here will facilitate a broader acceptance of IMS as a separation method of great potential by the communities of chromatography and electrophoresis, as well as that of mass spectrometry.

Ion Fragmentation and Filtering by Alpha Function in Ion Mobility Spectrometry for Improved Compound Differentiation.

Collision induced dissociation (CID) is a widely used technique in mass spectrometry to better understand the structural composition of ions and to improve the identification of compounds beyond the analysis of m/z. By increasing the kinetic energy of ions in an electric field, the collisions with neutral molecules may result in bond breakage, dissociation, or fragmentation of the molecular ion into smaller fragments if the necessary onset energy is exceeded. In this work and for the first time, we demonstrate CID in a field asymmetric time of flight ion mobility spectrometer (FAT-IMS). In contrast to the commonly used devices in mass spectrometry, the FAT-IMS operates at ambient pressure and temperature. Furthermore, the FAT-IMS allows separation of ions prior to dissociation, employing the shift occurring in the FAT region and, thus, an improved assignment of fragment ions to selected precursor ions. In this work, the effect of the operation parameters on the fragmentation efficiency of the FAT separator is analyzed. As proof of concept, eight saturated alcohols were investigated. The results show the expected substance-specific fragmentation behavior, which can be used to generate additional orthogonal information about certain analytes via their fragmentation pattern. Furthermore, a method for prefiltering analytes in FAT-IMS by the alpha function is introduced to remove spectral interferences.

Ultra-high-resolution ion mobility spectrometry-current instrumentation, limitations, and future developments.

With recent advances in ionization sources and instrumentation, ion mobility spectrometers (IMS) have transformed from a detector for chemical warfare agents and explosives to a widely used tool in analytical and bioanalytical applications. This increasing measurement task complexity requires higher and higher analytical performance and especially ultra-high resolution. In this review, we will discuss the currently used ion mobility spectrometers able to reach such ultra-high resolution, defined here as a resolving power greater than 200. These instruments are drift tube IMS, traveling wave IMS, trapped IMS, and field asymmetric or differential IMS. The basic operating principles and the resulting effects of experimental parameters on resolving power are explained and compared between the different instruments. This allows understanding the current limitations of resolving power and how ion mobility spectrometers may progress in the future. Graphical abstract.

Fast Orthogonal Separation by Superposition of Time of Flight and Field Asymmetric Ion Mobility Spectrometry.

Ion mobility spectrometry is a powerful and low-cost technique for the identification of chemical warfare agents, toxic chemicals, or explosives in air. Drift tube ion mobility spectrometers (DT-IMS) separate ions by the absolute value of their low field ion mobility, while field asymmetric ion mobility spectrometers (FAIMS) separate them by the change of their ion mobility at high fields. However, using one of these devices alone, some common and harmless substances show the same response as the hazardous target substances. In order to increase the selectivity, orthogonal data are required. Thus, in this work, we present for the first time an ambient pressure ion mobility spectrometer which is able to separate ions both by their differential and low field mobility, providing additional information for selectivity enhancement. This novel field asymmetric time of flight ion mobility spectrometer (FAT-IMS) allows high repetition rates and reaches limits of detection in the low ppb range common for DT-IMS. The device consists of a compact 44 mm drift tube with a tritium ionization source and a resolving power of 70. An increased separation of four substances with similar low field ion mobility is shown: phosgene (K0 = 2.33 cm2/(V s)), 1,1,2-trichlorethane (K0 = 2.31 cm2/(V s)), chlorine (K0 = 2.24 cm2/(V s)), and nitrogen dioxide (K0 = 2.25 cm2/(V s)). Furthermore, the behavior and limits of detection for acetonitrile, dimethyl methylphosphonate, diisopropyl methyl phosphonate in positive polarity and carbon dioxide, sulfur dioxide, hydrochloric acid, cyanogen chloride, and hydrogen cyanide in negative polarity are investigated.

High-Resolution High Kinetic Energy Ion Mobility Spectrometer Based on a Low-Discrimination Tristate Ion Shutter.

High kinetic energy ion mobility spectrometry (HiKE-IMS) allows for sensitive trace gas analysis within seconds, mitigating many disadvantages of standard ion mobility spectrometers through operation at reduced pressure and high electric field strengths. However, these advantages usually come at the cost of reduced resolving power, ranging from a maximum of 75 down to 50 at a reduced field strength of 120 Td for the original device. In this work, we present an extended theory for HiKE-IMS resolving power and a novel tristate ion shutter principle able to achieve initial ion packet widths of 1 µs without significant mobility discrimination. Such an ultrashort injection time allows for improving the resolving power of the HiKE-IMS to 140 for a wide range of reduced electric field strengths. With this resolving power, separating all ion species generated from a mixture of benzene, toluene, and xylene is possible. Furthermore, a resolving power of 140 is sufficient to partially separate isotopologues under high electric field strengths.

Separation of Isotopologues in Ultra-High-Resolution Ion Mobility Spectrometry.

Ion mobility spectrometry provides ion separation in the gas phase mainly based on differing ion-neutral collision cross sections, enabling powerful analysis of many isomers. However, the separation also has a miniscule mass dependence due to the acceleration and collision properties. In this work, we show for the first time that using a compact ultra-high-resolution ion mobility spectrometer with a resolving power of 250 and an UV ionization source enables the separation of isotopologues with ion mobility spectrometry. This is demonstrated for regular and perdeuterated acetone, benzene, and toluene as well as toluene-13C7 in nitrogen and in purified air as drift gas. The observed peak shifts in the ion mobility spectrum agree with the basic ion mobility equation when using nitrogen as drift gas and also agree with a combination of this equation with Blanc's law when using purified air as drift gas. For benzene and toluene, a reduction in the ion-neutral collision cross section of the isotopically replaced species is observed. Furthermore, a third peak formed from regular and perdeuterated acetone is observed, which can most likely be attributed to the exchange of a methyl group.

A compact high resolution ion mobility spectrometer for fast trace gas analysis.

Drift tube ion mobility spectrometers (IMS) are widely used for fast trace gas detection in air, but portable compact systems are typically very limited in their resolving power. Decreasing the initial ion packet width improves the resolution, but is generally associated with a reduced signal-to-noise-ratio (SNR) due to the lower number of ions injected into the drift region. In this paper, we present a refined theory of IMS operation which employs a combined approach for the analysis of the ion drift and the subsequent amplification to predict both the resolution and the SNR of the measured ion current peak. This theoretical analysis shows that the SNR is not a function of the initial ion packet width, meaning that compact drift tube IMS with both very high resolution and extremely low limits of detection can be designed. Based on these implications, an optimized combination of a compact drift tube with a length of just 10 cm and a transimpedance amplifier has been constructed with a resolution of 183 measured for the positive reactant ion peak (RIP(+)), which is sufficient to e.g. separate the RIP(+) from the protonated acetone monomer, even though their drift times only differ by a factor of 1.007. Furthermore, the limits of detection (LODs) for acetone are 180 pptv within 1 s of averaging time and 580 pptv within only 100 ms.

A High Kinetic Energy Ion Mobility Spectrometer for Operation at Higher Pressures of up to 60 mbar.

High Kinetic Energy Ion Mobility Spectrometers (HiKE-IMS) are usually operated at absolute pressures around 20 mbar in order to reach high reduced electric field strengths of up to 120 Td for influencing reaction kinetics in the reaction region. Such operating points significantly increase the linear range and limit chemical cross sensitivities. Furthermore, HiKE-IMS enables ionization of compounds normally not detectable in ambient pressure IMS, such as benzene, due to additional reaction pathways and fewer clustering reactions. However, operation at higher pressures promises increased sensitivity and smaller instrument size. In this work, we therefore study the theoretical requirements to prevent dielectric breakdown while maintaining high reduced electric field strengths at higher pressures. Furthermore, we experimentally investigate influences of the pressure, discharge currents and applied voltages on the corona ionization source. Based on these results, we present a HiKE-IMS that operates at a pressure of 60 mbar and reduced electric field strengths of up to 105 Td. The corona experiments show shark fin shaped curves for the total charge at the detector with a distinct optimum operating point in the glow discharge region at a corona discharge current of 5 µA. Here, the available charge is maximized while the generation of less-reactive ion species like NOx+ is minimized. With these settings, the reactant ion population, H3O+ and O2+, for ionizing and detecting nonpolar substances like n-hexane is still available even at 60 mbar, achieving a limit of detection of just 5 ppbV for n-hexane.