Ion mobility calculations of flexible all-atom systems at arbitrary fields using two-temperature theory.

Ion mobility spectrometry (IMS) separates and analyzes ions based on their mobility in a gas under an electric field. When the field is increased, the mobility varies in a complex way that depends on the relative velocity between gas and ion, their electrostatic potential interactions, and the effects from direct impingement. Recently, the two-temperature theory, primarily developed for monoatomic ions in monoatomic gases, has been extended to study mobilities at arbitrary fields using polyatomic ions in polyatomic gases, with some success. However, this extension poses challenges, such as inelastic collisions between gas and ion and structural modifications of ions as they heat up. These challenges become significant when working with diatomic gases and flexible molecules. In a previous study, experimental mobilities of tetraalkylammonium salts were obtained using a FAIMS instrument, showing satisfactory agreement with numerical two-temperature theory predictions. However, deviations occurred at fields greater than 100 Td. To address this issue, this paper introduces a modified high-field calculation method that accounts for the structural changes in ions due to field heating. The study focuses on tetraheptylammonium (THA+), tetradecylammonium (TDA+), and tetradodecylammonium (TDDA+) salts. Molecular structures were generated at various temperatures using MM2 forcefield. The mobility was calculated using IMoS 1.13 with two-temperature trajectory method calculations up to the fourth approximation. Multiple effective temperatures were considered, and a linear weighing system was used to create mobility vs. reduced field strength plots. The results suggest that the structural enlargement due to ion heating plays a significant role in mobility at high fields, aligning better with experimental data. FAIMS' dispersion plots also show improved agreement with experimental results. However, the contribution of inelastic collisions and energy transfer to rotational degrees of freedom in gas molecules remains a complex and challenging aspect.

Investigation of Zero-/High-Field Ion Mobility Orthogonal Separation Using a Hyphenated DMA-FAIMS System and Validation of the Two-Temperature Theory at Arbitrary Field for Tetraalkylammonium Salts in Nitrogen.

Toward greater separation techniques for ions, a differential mobility analyzer (DMA) has been coupled with field asymmetric waveform ion mobility spectrometry (FAIMS) to take advantage of two mobility-related but different methods of separation. The filtering effect of the DMA allows ions to be selected individually based on low-field mobility and studied in FAIMS at variable electric field, yielding mobility separations in two dimensions. Because spectra fully describe ion mobility at variable field strength, results are then compared with a two-temperature theory-predicted mobility up to the fourth-order approximation. The comparison yields excellent results up to at least 100 Td, beyond which the theory deviates from experiments. This is attributed to two effects, the enlargement of the structure due to ion heating and the inelasticity of the collisions with the nitrogen bath gas. The corrected mobility can then be used to predict the dispersion plot through a newly developed implicit equation that circumvents the possible issues related to the more elaborate Buryakov equation. Our results simultaneously show that the DMA-FAIMS coupling yields complete information on ion mobility versus the field-strength to gas-density ratio and works toward predicting such spectra from ion structures and gas properties.

Flow-Optimized Model for Gas Jet Desorption Sampling Mass Spectrometry.

Thermal gas jet probes, including post-plasma desorption/ionization sources, have not been studied using computational fluid dynamics (CFD) models, as have other ambient mass spectrometry sampling techniques. Two systems were constructed: a heated nitrogen jet probe to establish practical bounds for a sampling/transmission experiment and a CFD model to study trajectories of particles desorbed from a surface through optimization of streamlines and temperatures. The physical model configuration as tested using CFD revealed large losses, transmitting less than 10% of desorbed particles. Different distances between the desorption probe and the transport tube and from the sample surface were studied. The transmission improved when the system was very close to the sample, because the gas jet otherwise creates a region of low pressure that guides the streamlines below the inlet. A baffle positioned to increase pressure in the sample region improves collection efficiency. A Lagrangian particle tracking approach confirms the optimal design leading to a transmission of almost 100%.

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.

Enhancing Separation and Constriction of Ion Mobility Distributions in Drift Tubes at Atmospheric Pressure Using Varying Fields.

A linearly decreasing electric field has been previously proven to be effective for diffusional correction of ions in a varying field drift tube (VFDT) system, leading to higher resolving powers compared to a conventional drift tube due to its capacity to narrow distributions midflight. However, the theoretical predictions in resolving power of the VFDT were much higher than what was observed experimentally. The reason behind this discrepancy has been identified as the difference between the theoretically calculated resolving power (spatial) and the experimental one (time). To match the high spatial resolving power experimentally, a secondary high voltage pulse (HVP) at a properly adjusted time is used to provide the ions with enough momentum to increase their drift velocity and hence their time-resolving power. A series of systematic numerical simulations and experimental tests have been designed to corroborate our theoretical findings. The HVP-VFDT atmospheric pressure portable system improves the resolving power from the maximum expected of 60-80 for a regular drift tube to 250 in just 21 cm in length and 7kV, an unprecedent accomplishment.

Instantaneous Differentiation of Functional Isomers via Reactive Flowing Atmospheric Pressure Afterglow Mass Spectrometry.

Ambient mass spectrometry (AMS) allows direct desorption and ionization of analytes in real time with minimal-to-no sample preparation. However, it may present inadequate capabilities for differentiating isomers. Here, a reactive flowing atmospheric-pressure afterglow (reactive-FAPA) AMS source is developed for rapid isomer differentiation by derivatization of analytes in real time. The effects of the reactive-FAPA operating conditions on the reagent and product ions were studied and optimized for highly volatile and non-volatile model compounds with different carbonyl functional groups. In addition, two functional isomers of valproic acid (VPA) metabolites, 4-ene VPA and γ-valprolactone, are successfully differentiated for the first time by incorporating methylamine (MA) reagent vapor into the plasma effluent used for desorption/ionization. Reactive-FAPAMS for 4-ene VPA shows only detectable peaks of the protonated acylation product [M + MA-H2O + H]+, while for γ-valprolactone, it shows detectable peaks for both protonated acylation product [M + MA-H2O + H]+ and protonated intermediate [M + MA + H]+. A method for quantitative characterization of mixtures of 4-ene VPA and γ-valprolactone is also developed and validated. In addition, reactive-FAPAMS also shows better detection sensitivity compared to nonreactive-FAPAMS for some larger analyte types, such as UV filters and steroids. The limit of detection (LOD) of pregnenolone acetate in reactive-FAPAMS is 310 ng/mL, which is about 10 times better than its LOD in nonreactive-FAPA.

Flowing atmospheric-pressure afterglow drift tube ion mobility spectrometry.

In this work, the flowing atmospheric-pressure afterglow (FAPA) ambient desorption/ionization source has been coupled with stand-alone Drift Tube Ion Mobility Spectrometry (DTIMS) for the first time. A tip repeller electrode, modified to allow higher bias potential still below the Townsend's breakdown, was implemented at the FAPA/DTIMS interface to overcome the opposing potentials and facilitate ion transmission. The effect of the lab-built DTIMS and FAPA's operating conditions (such as plasma voltage, current, gas flow rate, repeller's potential and positioning, FAPA orientation, etc.) on the signal of selected analytes was studied, for both gas-phase injection and desorption. The FAPA reactant ion peak (RIP) reduced mobility coefficient (K0) corresponds to protonated water clusters (H2O)nH+. The FAPA-DTIMS spectra of several selected compounds showed that their K0 agrees with literature values. Moreover, quantitative characterization of acetaminophen and 2,6-di-tert-butylpyridine (2,6-DTBP) based on desorption or gas-phase injection yield limits of detection (LODs) of 0.03 µg and 18 ppb, respectively.

Diagnostic accuracy of colposcopic examination in patients with oral dysplastic lesions.

OBJECTIVE: Colposcopy is a direct microscopic method and is the gold standard tool to detect early cervical dysplastic lesions. In the past, many attempts have been made to use gynecologic methods to examine the oral mucosa. The aim of this study was to detect the diagnostic accuracy of oral colposcopy in diagnosing oral dysplastic lesions in comparison with microscopic evaluation based on biopsy and compare Reid's Colposcopic Index (RCI) and the Swede scoring system in diagnosing oral dysplastic lesions. STUDY DESIGN: Twenty-five patients who presented for diagnosis of oral leukoplakia to the Oral Medicine and Periodontology Department, Faculty of Dentistry, Cairo University (Cairo, Egypt) and met the selection criteria were recruited in this study. Each patient was subjected to colposcopic examination, followed by biopsy to confirm the results of colposcopy. The sensitivity and specificity of oral colposcopy were calculated after colposcopic assessment by using the Swede scoring system and the RCI. RESULTS: The diagnostic accuracy of oral colposcopy with use of the Swede scoring system was superior to that of oral colposcopy with the use of the RCI. CONCLUSIONS: Colposcopic examination using the Swede scoring system is very specific for diagnosing oral epithelial dysplasia and for using the "see-and-treat" method, whereas the RCI is a very sensitive screening method for the diagnosis of oral epithelial dysplasia in oral potentially malignant disorders.