Drift Tube Ion Mobility Spectrometry Research Articles

Interplatform comparison between three ion mobility techniques for human plasma lipid collision cross sections

The implementation of ion mobility spectrometry (IMS) in liquid chromatography-high-resolution mass spectrometry (LC-HRMS) workflows has become a valuable tool for improving compound annotation in metabolomics analyses by increasing peak capacity and by adding a new molecular descriptor, the collision cross section (CCS). Although some studies reported high repeatability and reproducibility of CCS determination and only few studies reported good interplatform agreement for small molecules, standardized protocols are still missing due to the lack of reference CCS values and reference materials.We present a comparison of CCS values of approximatively one hundred lipid species either commercially available or extracted from human plasma. We used three different commercial ion mobility technologies from different laboratories, drift tube IMS (DTIMS), travelling wave IMS (TWIMS) and trapped IMS (TIMS), to evaluate both instrument repeatability and interlaboratory reproducibility. We showed that CCS discrepancies of 0.3% (average) could occur depending on the data processing software tools. Moreover, eleven CCS calibrants were evaluated yielding mean RSD below 2% for eight calibrants, ESI Low concentration tuning mix (Tune Mix) showing the lowest RSD (< 0.5%) in both ion modes. Tune Mix calibrated CCS from the three different IMS instruments proved to be well correlated and highly reproducible (R2 > 0.995 and mean RSD ≤ 1%). More than 90% of the lipid CCS had deviations of less than 1%, demonstrating high comparability between techniques, and the possibility to use the CCS as molecular descriptor. We highlighted the need of standardized procedures for calibration, data acquisition, and data processing. This work demonstrates that using harmonized analytical conditions are required for interplatform reproducibility for CCS determination of human plasma lipids.

Measurement of very low-molecular weight metabolites by traveling wave ion mobility and its use in human urine samples

The collision cross-sections (CCS) measurement using ion mobility spectrometry (IMS) in combination with mass spectrometry (MS) offers a great opportunity to increase confidence in metabolite identification. However, owing to the lack of sensitivity and resolution, IMS has an analytical challenge in studying the CCS values of very low-molecular-weight metabolites (VLMs ≤ 250 Da). Here, we describe an analytical method using ultrahigh-performance liquid chromatography coupled to a traveling wave ion mobility-quadrupole-time-of-flight mass spectrometer optimized for the measurement of VLMs in human urine samples. The experimental CCS values, along with mass spectral properties were reported for the 174 metabolites. The experimental data included the mass-to-charge ratio (m/z), retention time (RT), tandem MS (MS/MS) spectra, and CCS values. Among the studied metabolites, 263 traveling wave ion mobility spectrometry (TWIMS)-derived CCS values (TWCCSN2) were reported for the first time, and more than 70% of these were CCS values of VLMs. The TWCCSN2 values were highly repeatable, with inter-day variations of < 1% RSD. The developed method revealed excellent TWCCSN2 accuracy with a CCS difference (ΔCCS) within ±2% of the reported drift tube IMS (DTIMS) and TWIMS CCS values. The complexity of the urine matrix did not affect the precision of the method, as evidenced by ΔCCS within ±1.92%. According to the Metabolomics Standards Initiative, 55 urinary metabolites were identified with a confidence level of 1. Among these 55 metabolites, 53 (96%) were VLMs. The larger number of confirmed compounds found in this study was a result of the addition of TWCCSN2 values, which clearly increased metabolite identification confidence.

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.

Enhancing ion mobility spectrometry performance through a programmable ion swarm shaping method based on Bradbury-Nielsen gates

The ion gate is a critical element in drift tube ion mobility spectrometry (IMS) as it directly influences the resolving power and sensitivity of the system. However, the conventional Bradbury-Nielsen gate (BNG) often leads to deformation of the ion swarm shape, resulting in reduced resolving power and significant discrimination effects. To address these limitations, we propose a novel method that incorporates a cutting phase following the gate opening. This approach effectively reduces trailing edge deformation, resulting in a maximum resolving power of over 100 and increased signal intensity. Additionally, this method maintains high resolving power even during longer gate opening times. Remarkably, this method not only significantly reduces the mobility discrimination effect but also enables the achievement of reverse discrimination by adjusting the duration of the cutting phase. Consequently, it demonstrates the potential to selectively amplify the peak height of target ions. Our method offers straightforward implementation across all IMS systems utilizing the BNG, thereby significantly improving system performance.

Molecular Dynamics-Based Modeling of Ion-Neutral Collisions in an Open Ion Trajectory Simulation Framework.

Ion mobility spectrometry (IMS) and ion mobility mass spectrometry (IMS-MS) methods have become increasingly popular and are important analytical techniques to determine information about the structural parameters of gas-phase analytes. The accurate description of the interaction between molecular ions and neutral background gas particles is an essential part of high-quality simulations of such modern mass- and ion-mobility-spectrometric systems. Established ion-neutral collision models (Hard-sphere collision modeling and statistical diffusion simulations) in common ion-trajectory simulation systems like SIMION use strongly simplified assumptions and are thus limited in their predictive ability. In contrast, collision cross-section (CCS) modeling programs (e.g., MOBCAL, IMoS, and Colloidoscope) allow high-quality ion mobility predictions for low-field equilibrium conditions using explicit scattering processes with a molecular dynamics-based trajectory method but cannot be used for nonequilibrium collision modeling in an ion trajectory simulation. This work presents an extension to the open-source Ion Dynamics Simulation Framework (IDSimF), which allows the simulation of ion dynamics under arbitrary and even nonequilibrium conditions. It was extended by an advanced collision model employing the molecular dynamics trajectory method for a detailed microscopic description of ion-neutral collisions within ion-trajectory simulations. We used drift tube ion mobility spectrometry (DT-IMS) to validate the predictive abilities of the model and to estimate the runtime requirements for productive simulations. Simulated high-field ion mobilities for small ion systems in a drift tube IMS are compared to experimental values from the literature and an implementation of a hard-sphere model in IDSimF for helium and argon as background gas particles. Significant improvements in ion mobility predictions using the molecular dynamics trajectory approach are obtained with deviations of only a few percent from experimental values. Therefore, the established and publicly available MD collision model will serve as foundation for nonequilibrium ion dynamics simulations and the development of improved ion dynamics modeling methods.

Improvement of untargeted proteomics workflow for surfaceome profiling and its evaluation through the implementation of quality controls: Application to multiple myeloma

BackgroundComprehensive surfaceome profiling of cancer cells using mass spectrometry (MS)-based technologies is a valuable approach to identify new antigens that could be targeted by immunotherapies. Multiple myeloma (MM) is an incurable hematological malignancy in which patients suffer from multiple relapses associated with drug resistance. Nevertheless, only three MM-specific antigens are currently targeted by approved immunotherapies which restrain the availability of efficient treatments for severe refractory patients affected by aggressive forms of the disease. Therefore, the discovery of new antigens in this context could open new perspectives for those patients. ResultsIn this study, the first objective was to improve a MS-based untargeted proteomics workflow in order to handle limited patient samples. For this purpose, a highly sensitive and robust miniaturized separation system (LC-Chip) coupled with drift tube ion mobility spectrometry and high-resolution MS was integrated in our workflow to maximize protein identification. As sample preparation can strongly influence the detectability of membrane-associated proteins, the critical steps in sample preparation were carefully optimized. As a result, 4.5 times more membrane-associated proteins were identified and experimental throughput was also drastically improved. In addition to workflow performance, particular attention was paid to assess the quality of the generated data. Indeed, several quality controls (QC) were implemented to assess data quality. Finally, the optimized workflow as well as selected QCs were evaluated in the analysis of samples containing limited number of cells. SignificanceThis work allowed the improvement of an untargeted proteomics workflow for surfaceome profiling in terms of performance. Besides, the reliability of the obtained data was evaluated through the introduction of QCs in the workflow. The applicability of the improved workflow as well as the implemented QCs for the analysis of MM primary cells obtained from patients was confirmed.

Simultaneous Ion Swarm Profiling and Ion Mobility Measurement using Ion Cameras.

When operated as a standalone analytical device, traditional drift tube ion mobility spectrometry (IMS) experiments require high-speed, high-gain transimpedance amplifiers to record ion separations with sufficient resolution. Recent developments in the fabrication of charge-sensitive cameras (e.g., IonCCD) have provided key insights for ion beam profiling in mass spectrometry and even served as detectors for miniature magnetic sector instruments. Unfortunately, these platforms have comparatively slow integration times (multiple ms), which largely precludes their use for recording ion mobility spectra, where sampling rates into the 10s of kHz are generally required. As a result, experiments that simultaneously probe the longitudinal and transverse mobility of an injected species using an array detector have not been reported. To address this duty-cycle mismatch, a frequency encoding strategy is used to evaluate ion swarm characteristics, while directly capturing ion mobility information using the Fourier transform. This apparatus described allows the ion beam to be profiled over the full course of the experiment and establishes the foundation to examine axial and longitudinal drift velocities simultaneously.

General Method to Obtain Collision Cross-Section Values in Multipass High-Resolution Cyclic Ion Mobility Separations.

In recent years, ion mobility spectrometry-mass spectrometry (IMS-MS) has advanced the field of omics-based research, especially with the development of high-resolution platforms; however, these separations have generally been qualitative in nature. The rotationally averaged ion neutral collision cross section (CCS) is one of the only quantitative metrics available for aiding in characterizing biomolecules in IMS-MS. However, determining the CCS of an ion for multipass IMS systems, such as in cyclic ion mobility-mass spectrometry (cIMS-MS) and structures for lossless ion manipulations, has been challenging due to the lack of methods available for calculating CCS when more than a single pass is required for separation as well as the laborious nature of requiring calibrants and unknown compounds to be subjected to identical number of passes, which may not be possible in certain instances because of peak splitting, high levels of diffusion, etc. Herein, we present a general method that uses average ion velocities for calculating CCS values in cIMS-MS-based separations. Initially, we developed calibration curves using common CCS calibrants [i.e., tetra-alkylammonium salts, polyalanine, and hexakis(fluoroalkoxy)phosphazines] at different traveling wave (TW) conditions and the calculated cIMS CCS values were within ∼1% error or less compared to previously established drift tube IMS CCS measurements. Since it has been established that glycans can split into their α/β anomers, we utilized this method for two glycan species, 2α-mannobiose and melibiose. Both glycans were analyzed at the same TW conditions as the calibrants, and we observed anomer splitting at pathlengths of 20 m for 2α-mannobiose and 40 m for melibiose and thus assigned two unique CCS values for each glycan, which is the first time this has ever been done. We have demonstrated that the use of average ion velocities is a robust approach for obtaining CCS values with good agreement to CCS measurements from the previous literature and anticipate that this methodology can be applied to any IMS-MS platform that utilizes multipass separations. Our future work aims to incorporate this methodology for the development of a high-resolution CCS database to aid in the characterization of human milk oligosaccharides.

Nonenzymatic Posttranslational Modifications and Peptide Cleavages Observed in Peptide Epimers.

Posttranslational modifications (PTMs) play vital roles in cellular homeostasis and are implicated in various pathological conditions. This work uses two ion mobility spectrometry-mass spectrometry (IMS-MS) modalities, drift-tube IMS (DT-IMS) and trapped IMS (TIMS), to characterize three important nonenzymatic PTMs that induce no mass loss: l/d isomerization, aspartate/isoaspartate isomerization, and cis/trans proline isomerization. These PTMs are assessed in a single peptide system, the recently discovered pleurin peptides, Plrn2, from Aplysia californica. We determine that the DT-IMS-MS/MS can capture and locate asparagine deamidation into aspartate and its subsequent isomerization to isoaspartate, a key biomarker for age-related diseases. Additionally, nonenzymatic peptide cleavage via in-source fragmentation is evaluated for differences in the intensities and patterns of fragment peaks between these PTMs. Peptide fragments resulting from in-source fragmentation, preceded by peptide denaturation by liquid chromatography (LC) mobile phase, exhibited cis/trans proline isomerization. Finally, the effects of differing the fragmentation voltage at the source and solution-based denaturation conditions on in-source fragmentation profiles are evaluated, confirming that LC denaturation and in-source fragmentation profoundly impact N-terminal peptide bond cleavages of Plrn2 and the structures of their fragment ions. With that, LC-IMS-MS/MS coupled with in-source fragmentation could be a robust method to identify three important posttranslational modifications: l/d isomerization, Asn-deamidation leading to Asp/IsoAsp isomerization, and cis/trans proline isomerization.

Molecular and Structural Characterization of Isomeric Compounds in Atmospheric Organic Aerosol Using Ion Mobility-Mass Spectrometry.

Secondary organic aerosol (SOA) formed through multiphase atmospheric chemistry makes up a large fraction of airborne particles. The chemical composition and molecular structures of SOA constituents vary between different emission sources and aging processes in the atmosphere, which complicates their identification. In this work, we employ drift tube ion mobility spectrometry with quadrupole time-of-flight mass spectrometry (IM-MS) detection for rapid gas-phase separation and multidimensional characterization of isomers in two biogenic SOAs produced from ozonolysis of isomeric monoterpenes, d-limonene (LSOA) and α-pinene (PSOA). SOA samples were ionized using electrospray ionization (ESI) and characterized using IM-MS in both positive and negative ionization modes. The IM-derived collision cross sections in nitrogen gas (DTCCSN2 ) for individual SOA components were obtained using multifield and single-field measurements. A novel application of IM multiplexing/high-resolution demultiplexing methodology was employed to increase sensitivity, improve peak shapes, and augment mobility baseline resolution, which revealed several isomeric structures for the measured ions. For LSOA and PSOA samples, we report significant structural differences of the isomer structures. Molecular structural calculations using density functional theory combined with the theoretical modeling of CCS values provide insights into the structural differences between LSOA and PSOA constituents. The average DTCCSN2 values for monomeric SOA components observed as [M + Na]+ ions are 3-6% higher than those of their [M - H]- counterparts. Meanwhile, dimeric and trimeric isomer components in both samples showed an inverse trend with the relevant values of [M - H]- ions being 3-7% higher than their [M + Na]+ counterparts, respectively. The results indicate that the structures of Na+-coordinated oligomeric ions are more compact than those of the corresponding deprotonated species. The coordination with Na+ occurs on the oxygen atoms of the carbonyl groups leading to a compact configuration. Meanwhile, deprotonated molecules have higher DTCCSN2 values due to their elongated structures in the gas phase. Therefore, DTCCSN2 values of isomers in SOA mixtures depend strongly on the mode of ionization in ESI. Additionally, PSOA monomers and dimers exhibit larger DTCCSN2 values (1-4%) than their LSOA counterparts owing to more rigid structures. A cyclobutane ring is present with functional groups pointing in opposite directions in PSOA compounds, as compared to noncyclic flexible LSOA structures, forming more compact ions in the gas phase. Lastly, we investigated the effects of direct photolysis on the chemical transformations of selected individual PSOA components. We use IM-MS to reveal structural changes associated with aerosol aging by photolysis. This study illustrates the detailed molecular and structural descriptors for the detection and annotation of structural isomers in complex SOA mixtures.

A High-Throughput Ion Mobility Spectrometry-Mass Spectrometry Screening Method for Opioid Profiling.

In 2017, the United States Department of Health and Human Services declared the widespread misuse and abuse of prescription and illicit opioids an epidemic. However, this epidemic dates back to the 1990s when opioids were extensively prescribed for pain management. Currently, opioids are still recommended for pain management, and given their abuse potential, rapid screening is imperative for patient treatment. Of particular importance is assessing pain management patient compliance, where evaluating drug use is crucial for preventing opioid abuse and potential overdoses. In this work, we utilized drift tube ion mobility spectrometry coupled with mass spectrometry (DTIMS-MS) to develop a rapid screening method for 33 target opioids and opioid urinary metabolites. Collision cross section values were determined for all target molecules using a flow-injection DTIMS-MS method, and clear differentiation of 27 out of the 33 opioids without prior chromatographic separation was observed when utilizing a high resolution demultiplexing screening approach. An automated solid phase extraction (SPE) platform was then coupled to DTIMS-MS for 10 s sample-to-sample analyses. This SPE-IMS-MS approach enabled the rapid screening of urine samples for opioids and presents a major improvement in sample throughput compared to traditional chromatographic analyses coupled with MS, which routinely take several minutes per sample. Overall, this vast reduction in analysis time facilitates a faster turn-around for patient samples, providing great benefits to clinical applications.

Characterization of a Modulated X-ray Source for Ion Mobility Spectrometry.

As a highly deployed field instrument for the detection of narcotics, explosives, and chemical warfare agents, drift tube ion mobility spectrometry relies heavily upon the performance of the ionization source and mechanism of ion beam modulation. For this instrumental platform, ion chemistry plays a critical role in the performance of the instrument from a sensitivity and selectivity perspective; however, a range of instrumental components also occupy pivotal roles. Most notably, the mechanism of ion modulation or ion gating is a primary contributor to peak width in a drift tube ion mobility experiment. Unfortunately, physical ion gates rarely perform perfectly, and in addition to serving as physical impediments to ion transmission, their modulation also has undesirable field effects. Using a recently developed modulated, non-radioactive X-ray source, we detail the performance of an ion mobility spectrometry (IMS) system that is free of a gating structure and utilizes the pulsed nature of the modulated X-ray source (MXS) for both ion generation and initiation of the IMS experiment. After investigating the influence of pulse duration and spatial X-ray beam width on the analytical performance of the instrument, the possibility of using multiplexing with a shutterless system is explored. By increasing ion throughput, the observed multiplexing gain compared to a signal-averaged spectrum approaches the theoretical maximum and illustrates the capability of the MXS-IMS system to realize significant signal to noise improvements.

A re-calibration procedure for interoperable lipid collision cross section values measured by traveling wave ion mobility spectrometry

Collision cross sections (CCS) have been described as relevant molecular descriptors in metabolomics and lipidomics analyses for ascertaining compound identity. Ion mobility spectrometry (IMS) allows to determine CCS with different techniques, such as drift tube ion mobility spectrometry (DTIMS), traveling wave ion mobility spectrometry (TWIMS) or trapped ion mobility spectrometry (TIMS). In contrast with DTIMS where CCS can be obtained directly with measured drift times and mathematical relationship, TWIMS and TIMS techniques require an additional step of calibration to obtain CCS values. However, literature reports significantly disparate CCS values depending on the calibrant used (often more than 10%), as no consensus has been reached to define a universal CCS reference standard or harmonized calibration procedure. Therefore, publicly available CCS databases cannot be regarded as readily interoperable and exchangeable.Here, we performed a comprehensive evaluation of 11 distinct CCS calibrants in a traveling wave ion mobility spectrometry-mass spectrometry (TWIMS-MS) instrument. We showed that, using lipids from plasma as model compounds, CCS determination drastically fluctuates from one calibrant to the other with up to 25% differences, which precludes direct CCS comparison. Using the large panel of calibration curves generated, we showed that any CCS value can be efficiently re-calibrated relatively to the calibration curve made with the widely used Tune Mix solution whatever the calibration procedure originally used. The re-calibrated CCS values for each calibrant constitute a database which allows to correct any deviation on lipid CCS values whatever the calibrant originally used. Resulting corrected CCS values from plasma lipids were thus efficiently matched to those previously reported in the literature (with deviations<2%). Therefore, this work shows that unique and comparable CCS values can be obtained upon re-calibration relatively to Tune Mix CCS values, while also paving the way for the establishment of a universal CCS database of various metabolite or lipid classes.

Trapped ion mobility spectrometry-mass spectrometry improves the coverage and accuracy of four-dimensional untargeted lipidomics

Lipids play vital roles in many physiological and pathological processes in living organisms. Due to the high structural diversity and the numerous isomers and isobars of lipids, high-coverage and high-accuracy lipidomic analysis of complex biological samples remain the bottleneck to investigate lipid metabolism. Here, we developed the trapped ion mobility spectrometry-mass spectrometry (TIMS-MS) based four-dimensional untargeted lipidomics to support accurate lipid identification and quantification in biological samples. We first demonstrated that the TIMS based multi-dimensional separation improved the differentiations of isomeric and isobaric lipids, and increased the purity of precursor ion isolation and the quality of MS/MS spectra. Hyphenation of TIMS and PASEF technologies significantly improved the coverages of MS/MS spectra. These technological advantages jointly improved the coverage and accuracy of lipid identification in untargeted lipidomics. We further demonstrated that the CCS values of lipids acquired using TIMS were highly consistent with those from drift tube ion mobility spectrometry (DTIMS). Lipid identification and quantification results of NIST human plasma samples were also verified with inter-laboratory reports. Finally, we applied the TIMS-MS based untargeted lipidomics to characterize the spatial distributions of 1393 distinctive lipids in the mouse brain, and demonstrated that diverse lipid distributions and compositions among brain regions contributed to different functions of brain regions. Altogether, TIMS-MS based four-dimensional untargeted lipidomics significantly improved the coverage and accuracy of untargeted metabolomics, thereby facilitating a system-level understanding of lipid metabolism in biological organisms.

Effect of Traveling Waveform Profiles on Collision Cross Section Measurements in Structures for Lossless Ion Manipulations.

We evaluated the effect of four different waveform profiles (Square, Sine, Triangle, and asymmetric Sawtooth) on the accuracy of collision cross section (CCS) measurements using traveling wave ion mobility spectrometry (TWIMS) separations in structures for lossless ion manipulations (SLIM). The effects of the waveform profiles on the accuracy of the CCS measurements were evaluated for four classes of compounds (lipids, peptides, steroids, and nucleosides) at different TW speeds (126-206 m/s) and amplitudes (15-89 V). For the lipids and peptides, the TWIMS-based CCS (TWCCS) deviations from the corresponding drift-tube-based CCS (DTCCS) measurements were significantly lower in experiments conducted using the Sawtooth waveform compared to the square waveform. This observation can be rationalized by the lower maximum electric field experienced by ions with a Sawtooth waveform, as compared to the other waveforms, resulting in a lower probability for significant ion heating. We also observed that given approximately comparable resolution for all four waveforms, the Sawtooth waveform resulted in lower TWCCS error and a better agreement with DTCCS values than the Square waveform. In addition, for the steroids and nucleosides, an opposite TWCCS trend was observed, with higher errors with the Sawtooth waveform and lower with the Square waveform, suggesting that these molecules tend to become slightly more compact under ion heating conditions. Under optimum conditions, all TWCCS measurements on the SLIM platform were within 0.5% of those measured in the drift tube ion mobility spectrometry.

Enhanced Ion Mobility Separation and Characterization of Isomeric Phosphatidylcholines Using Absorption Mode Fourier Transform Multiplexing and Ultraviolet Photodissociation Mass Spectrometry.

The structural diversity of phospholipids plays a critical role in cellular membrane dynamics, energy storage, and cellular signaling. Despite its importance, the extent of this diversity has only recently come into focus, largely owing to advances in separation science and mass spectrometry methodology and instrumentation. Characterization of glycerophospholipid (GP) isomers differing only in their acyl chain configurations and locations of carbon-carbon double bonds (C═C) remains challenging due to the need for both effective separation of isomers and advanced tandem mass spectrometry (MS/MS) technologies capable of double-bond localization. Drift tube ion mobility spectrometry (DTIMS) coupled with MS can provide both fast separation and accurate determination of collision cross section (CCS) of molecules but typically lacks the resolving power needed to separate phospholipid isomers. Ultraviolet photodissociation (UVPD) can provide unambiguous double-bond localization but is challenging to implement on the timescales of modern commercial drift tube time-of-flight mass spectrometers. Here, we present a novel method for coupling DTIMS with a UVPD-enabled Orbitrap mass spectrometer using absorption mode Fourier transform multiplexing that affords simultaneous localization of double bonds and accurate CCS measurements even when isomers cannot be fully resolved in the mobility dimension. This method is demonstrated on two- and three-component mixtures and shown to provide CCS measurements that differ from those obtained by individual analysis of each component by less than 1%.

Field-Switching Repeller Flowing Atmospheric-Pressure Afterglow Drift Tube Ion Mobility Spectrometry.

In this work, a field-switching (FS) technique is employed with a flowing atmospheric pressure afterglow (FAPA) source in drift tube ion mobility spectrometry (DTIMS). The premise is to incorporate a tip-repeller electrode as a substitute for the Bradbury-Nielsen gate (BNG) so as to overcome corresponding disadvantages of the BNG, including the gate depletion effect (GDE). The DTIMS spectra were optimized in terms of peak shape and full width by inserting an aperture at the DTIMS inlet that was used to control the neutral molecules' penetration into the separation region, thus preventing neutral-ion reactions inside. The FAPA and repeller's experimental operating conditions including drift and plasma gas flow rates, pulse injection times, repeller positioning and voltage, FAPA current, and effluent angle were optimized. Ion mobility spectra of selected compounds were captured, and the corresponding reduced mobility values were calculated and compared with the literature. The 6-fold improvements in limit of detection (LOD) compared with previous work were obtained for 2,6-DTBP and acetaminophen. The enhanced performance of the FS-FAPA-DTIMS was also investigated as a function of the GDE when compared with FAPA-DTIMS containing BNG.

An atmospheric pressure field effect ionisation source for ion mobility spectrometry.

An atmospheric Pressure Field Effect (APFE) ionisation source for drift tube ion mobility spectrometry has been developed for operation in positive and negative polarities. The formation of negative and positive ions in synthetic air was studied and compared with the Atmospheric Pressure Corona Discharge (APCD) ionisation source. The APFE ionisation source is of point-to-plane geometry with a 10 μm Pt point electrode, a stainless steel plate electrode and ultra-high resistance (20 GΩ) current limiters. In the case of negative polarity, the ionisation source was able to generate Reactant Ions (RIs) O2-(H2O)n and O2-CO2(H2O)n, and in the case of positive polarity, stable production of H+(H2O)n RI was achieved in two different gas flow regimes of the IMS. RIs formed in the APFE in both polarities have made it a reliable chemical ionisation source at atmospheric pressure. The identification of the ions generated in the APFE was performed using an Ion Mobility Spectrometer coupled with an orthogonal acceleration Time of Flight Mass Spectrometer (IMS-oa-TOF-MS). The chemical ionisation of molecules was demonstrated for the APFE ionisation source in positive (2,6-di-tert-butyl-pyridine) and negative (tetrachloromethane) polarities.

Lennard-Jones interaction parameters of Mo and W in He and N2 from collision cross-sections of Lindqvist and Keggin polyoxometalate anions.

Drift tube ion mobility spectrometry (DTIMS) coupled with mass spectrometry was used to determine the collision cross-sections (DTCCS) of polyoxometalate anions in helium and nitrogen. As the geometry of the ion, more than its mass, determines the collision cross-section with a given drift gas molecule, we found that both Lindqvist ions Mo6O192- and W6O192- had a DTCCSHe value of 103 ± 2 Å2, and both Keggin ions PMo12O403- and PW12O403- had a DTCCSHe value of 170 ± 2 Å2. Similarly, ion mobility experiments in N2 led to DTCCSN2 values of 223 ± 2 Å2 and 339 ± 4 Å2 for Lindqvist and Keggin anions, respectively. Using optimized structures and partial charges determined from density functional theory calculations, followed by CCS calculations via the trajectory method, we determined Lennard-Jones 6-12 potential parameters ε, σ of 5.60 meV, 3.50 Å and 3.75 meV, 4.40 Å for both Mo and W atoms interacting with He and N2, respectively. These parameters reproduced the CCS of polyoxometalates within 2% accuracy.

On the separation of enantiomers by drift tube ion mobility spectrometry.

Racemic mixtures of twelve common α-amino acids and three chiral drugs were tested for the separation of their enantiomers by drift tube ion mobility spectrometry (IMS)-quadrupole mass spectrometry (QMS) by introducing chiral selectors into the buffer gas of the IMS instrument. (R)-α-(Trifluoromethyl)benzyl alcohol, (L)-ethyl lactate, methyl (S)-2-chloropropionate, and the R and S enantiomers of 2-butanol and 1-phenyl ethanol were evaluated as chiral selectors. Experimental conditions were varied during the tests, including buffer gas temperature, concentration and type of chiral selectors, analyte concentration, electrospray (ESI) voltage, ESI solvent pH, and buffer gas flow rate. The individual enantiomers yielded the same drift times and the racemic mixtures could not be separated. Energy calculations of the chiral selector-ion interactions showed that these separations are unlikely using 2-butanol as a chiral selector but they might be theoretically feasible depending on the chiral selector nature and the type of enantiomers. Several plausible explanations for not achieving separations were analyzed. Recommendations for potential enantiomer separations by IMS are proposed.