Drift Tube Research Articles

Conservation of the Charge in Signal from Drift Tube Ion Mobility Spectrometers.

Quantitative information obtained from drift tube detectors used in ion mobility spectrometry is contained in the area of peaks forming the drift time spectrum. The area of all peaks corresponds to the total charge of ions entering the drift section of the spectrometer. It was found that this charge is not conserved when the ion composition changes. This work is devoted to studying the causes of this phenomenon. Experimental research consisted of recording drift time spectra for 2-pentanone and n-heptanone, at various analyte concentrations and different opening times of the shutter grid. Measurements of the total ion current were also performed in static mode with an open grid. The research results indicated that the reasons for the lack of ion charge conservation in the drift time spectrum are ion recombination, mutual repulsion, and mobility-dependent transmission of ions through the shutter grid. The explanation of the relationships obtained experimentally was based on a simple theoretical model, which considered the phenomenon of ion transport along the reaction section and the penetration of ions through the shutter. The developed model provides a good description of the measurement results and allows the estimation of ion currents and ion concentrations in the reaction section upstream of the grid. This information is important for proper quantitative analysis as well as when the ion mobility spectrometer is used in quantitative studies of chemical ionization processes.

High Resolving Power Electrospray Ionization Ion Mobility Spectrometer Based on Fourier Deconvolution Multiplexing.

The resolving power of the drift tube ion mobility spectrometry (IMS) is mainly dependent on the drift length, the drift voltage, the pulse width of an ion gate, and the pressure inside the drift tube. Electrospray ionization (ESI)-IMS is a highly sensitive and reliable technique for the detection and analysis of nonvolatile compounds, and high resolving power is necessary to separate structurally similar compounds. To improve the analytical performance of atmospheric pressure ESI-IMS, the Fourier deconvolution (FD) multiplexing technique is investigated as an effective and convenient means to improve the resolving power as well as the signal-to-noise ratio. By reducing the equivalent ion gate opening width to 5 μs using a typical Tyndall-Powell ion shutter, a high resolving power RP up to 170 can be achieved with a drift length of 12 cm and a drift voltage of 10 kV. Rhodamine 6G (R6G), sodium dodecyl sulfate (SDS), methacycline, oxytetracycline, and ractopamine were evaluated using the FD-ESI-IMS, and mixtures with similar ion mobility can be well separated without prolonging the drift length.

Development of 10 m<sup>2</sup> hodoscope made of drift tubes for cosmic ray muon registration

The 10 m2 muon hodoscope made of drift tubes with length 3.7 m and diameter 52 mm is under development and construction in NRC “Kurchatov institute” — IHEP. Totally 768 drift tubes are grouped into 6 identical multilayers, each consisting of two tube layers with parallelly placed tubes. Tube orientation in adjacent multilayers is orthogonal, thus the hodoscope has six X and six Y tube layers. Detailed mechanical structure, on-chamber electronic and data acquisition systems are described. Expected technical characteristics and some test results are presented.

Advancing Protein Analysis: A Low-Pressure Drift Tube Orbitrap Mass Spectrometer for Ultraviolet Photodissociation-Based Structural Characterization.

Owing to its ability to generate extensive fragmentation of proteins, ultraviolet photodissociation (UVPD) mass spectrometry (MS) has emerged as a versatile ion activation technique for the structural characterization of native proteins and protein complexes. Interpreting these fragmentation patterns provides insight into the secondary and tertiary structures of protein ions. However, the inherent complexity and diversity of proteins often pose challenges in resolving their numerous conformations. To address this limitation, we combined UVPD-MS with drift tube ion mobility, offering potential to acquire conformationally selective MS/MS information. A low-pressure drift tube (LPDT) Orbitrap mass spectrometer equipped with 193 nm UVPD capabilities enables the analysis of protein conformers through the analysis of arrival time distributions (ATDs) of individual fragment ions. ATDs of fragment ions are compared for different backbone cleavage sites of the protein or different precursor charge states to give information about regions of potential folding or elongation. This integrated platform offers promise for advancing our understanding of protein structures in the gas phase.

Recent additions and access to a multidimensional lipidomic database containing liquid chromatography, ion mobility spectrometry, and tandem mass spectrometry information.

The importance of lipids in biology continues to grow with their recent linkages to more diseases and conditions, microbiome fluctuations, and environmental exposures. These associations have motivated researchers to evaluate lipidomic changes in numerous matrices and studies. Lipidomic analyses, however, present numerous challenges as lipid species have broad chemistries that require different extraction methods and instrumental analyses to evaluate and separate their many isomers and isobars. Increasing knowledge about different lipid characteristics is therefore crucial for improving their separation and identification. Here, we present a multidimensional database for lipids analyzed on a platform combining reversed-phase liquid chromatography, drift tube ion mobility spectrometry, collision-induced dissociation, and mass spectrometry (RPLC-DTIMS-CID-MS). This platform and the different separation characteristics it provides enables more confident lipid annotations when compared to traditional tandem mass spectrometry platforms, especially when analyzing highly isomeric molecules such as lipids. This database expands on our previous publication containing only human plasma and bronchoalveolar lavage fluid lipids and provides experimental RPLC retention times, IMS collision cross section (CCS) values, and m/z information for 877 unique lipids from additional biofluids and tissues. Specifically, the database contains 1504 precursor [M + H]+, [M + NH4]+, [M + Na]+, [M-H]-, [M-2H]2-, [M + HCOO]-, and [M + CH3COO]- ion species and their associated CID fragments which are commonly targeted in clinical and environmental studies, in addition to being present in the chloroform layer of Folch extractions. Furthermore, this multidimensional RPLC-DTIMS-CID-MS database spans 5 lipid categories (fatty acids, sterols, sphingolipids, glycerolipids, and glycerophospholipids) and 24 lipid classes. We have also created a webpage (tarheels.live/bakerlab/databases/) to enhance the accessibility of this resource which will be populated regularly with new lipids as we identify additional species and integrate novel standards.

Numerical and experimental study on manifold-distributed jet microchannel with micro-pin-fins

Traditional parallel microchannels are inadequate for managing the thermal requirements of newer, large-area and high-heat-flux chips. This inadequacy arises from its high flow resistance and poor temperature uniformity. Therefore, A novel manifold microchannel heat sink combining manifold inlet/outlet structures, distributed array jets, and micro pin-fins is introduced. Numerical simulations and experimental methods were employed to investigate the flow and heat transfer performance of the heat sink. Experimental results show that, with an average heat flux density exceeding 330 W/cm2 and a total power of 2500 W, the average chip temperature remains below 70 °C, ensuring efficient heat dissipation. Secondary impingement occurs at sufficiently low jet chamber heights, resulting in an increase of 3 times in the average Nusselt number for a smooth base plate. For the micro-pin-finned surface, it is shown that the presence of micro-pin-fins is not necessarily conducive to heat transfer enhancement. A critical volume fraction of micro-pin-fins (critical fin-ratio) exists where the obstructive effect and enhancement effect balance each other out. This value is influenced by multiple parameters. Finally, a novel relationship for predicting the average Nusselt number of jet impingement was proposed, with an average absolute error of less than 15 %. This series of investigations addresses the existing gaps in research on manifold-distributed array jet heat sinks and provides a meticulous theoretical foundation for the design and optimization of heat sinks facing the high-power chips.

Design and construction of the cylindrical drift chamber for the COMET Phase-I experiment

COMET is an experiment at J-PARC that searches for the charged lepton flavor violating process of neutrino-less muon-to-electron conversion (μ→e conversion) in a muonic atom. The COMET Phase-I experiment, which represents the first stage of its staged approach, utilizes the cylindrical drift chamber (CDC) as the main detector to measure the momentum of electrons emitted from μ→e conversion in a 1 T magnetic field. The CDC is designed for optimal performance to achieve the best momentum resolution and effectively separate the μ→e conversion electron signal from background signals. This design entails adapting He:i-C4H10 (90:10) as its chamber gas and employing an all-stereo wire configuration. This document provides a comprehensive overview of the CDC detector, encompassing design considerations, mechanical structure, construction methodologies, and results of performance evaluations conducted using cosmic-rays.

An Untargeted Lipidomics Workflow Incorporating High-Resolution Demultiplexing (HRdm) Drift Tube Ion Mobility-Mass Spectrometry.

Global discovery lipidomics can provide comprehensive chemical information toward understanding the intricacies of metabolic lipid disorders such as dyslipidemia; however, the isomeric complexity of lipid species remains an analytical challenge. Orthogonal separation strategies, such as ion mobility (IM), can be inserted into liquid chromatography-mass spectrometry (LC-MS) untargeted lipidomic workflows for additional isomer separation and high-confidence annotation, and the emergence of high-resolution ion mobility (HRIM) strategies provides marked improvements to the resolving power (Rp > 200) that can differentiate small structural differences characteristic of isomers. One such HRIM strategy, high-resolution demultiplexing (HRdm), utilizes multiplexed drift tube ion mobility spectrometry (DTIMS) with post-acquisition algorithmic deconvolution to access high IM resolutions while retaining the measurement precision inherent to the drift tube technique; however, HRdm has yet to be utilized in untargeted studies. In this manuscript, a proof-of-concept study using ATP10D dysfunctional murine models was investigated to demonstrate the utility of HRdm-incorporated untargeted lipidomic analysis pipelines. Total lipid features were found to increase by 2.5-fold with HRdm compared to demultiplexed DTIMS as a consequence of more isomeric lipids being resolved. An example lipid, PC 36:5, was found to be significantly higher in dysfunctional ATP10D mice with two resolved peaks observed by HRdm that were absent in both the functional ATP10D mice and the standard demultiplexed DTIMS acquisition mode. The benefits of utilizing HRdm for discerning isomeric lipids in untargeted workflows have the potential to enhance our analytical understanding of lipids related to disease complexity and biologically relevant studies.

A hyper-fast gas chromatograph coupled to an ion mobility spectrometer with high repetition rate and flow-optimized ion source to resolve the short chromatographic peaks

By combining the high selectivity of a gas chromatograph (GC) with the high sensitivity and decent selectivity of an ion mobility spectrometer (IMS), GC-IMS have become increasingly popular in many applications. However, most GC suffer from long analysis times. In contrast, an hyper-fast GC allows for extremely fast analysis in the tens of seconds while reaching comparably high resolution. In turn, coupling such hyper-fast GC with IMS requires sufficiently high repetition rate of recording full IMS spectra to resolve the short GC peaks. Therefore, we present a drift tube IMS with 100 Hz repetition rate. Key is a small effective detector volume combined with short drift length. Therefore, the ion source of the IMS combines a small reaction region with an extended field-switching ion shutter and optimized gas flows. To resolve even the shortest GC peaks with a full width at half maximum of 100 ms, a short drift length of just 41 mm was used, achieving a measurement time of 10 ms per spectrum and hence ten data points across the shortest GC peak. To avoid condensation of the sample, the entire IMS was heated isothermally to 120 °C. Despite short drift times and high temperatures, the IMS still reaches high resolving power of Rp = 60. The hyper-fast GC-IMS reaches low detection limits in the low ppbV range. For demonstration, ketone mixes and three different hop varieties were analyzed in <30 s.

Studies on the temperature dependent drift velocity for the HELIX Drift Chamber Tracker

HELIX (High Energy Light Isotope eXperiment) is a ballon experiment designed to measure abundance of cosmic ray isotopes from hydrogen to neon, with a particular interest in abundances of beryllium isotopes. HELIX aim to provide essential data to study the cosmic ray propagation in our galaxy. The Drift Chamber Tracker (DCT) in HELIX is a multi-wire gas drift chamber designed to measure the position of incident cosmic rays. It is located inside a magnet, bending the trajectory of incoming particles through 72-layers of tracking, enabling the measurement of the momentum of incoming particles.Before the data can be used for scientific analysis, the background must be taken out, and the instrument must be well calibrated. In order to exclude electronic noise from the DCT data it was necessary to determine the maximum drift velocity of each wire over a short period of time. To do this I developed an algorithm to be able to identify the maximum drift velocity for each wire over each dataset. This revealed a position dependence of the data within the detector. In order to attempt to characterize this dependence, so it can be accounted for in the calibration stage, I preformed a study on the temperature dependence of the drift velocities analyzing at data from different time periods over the course of the flight. To characterize this dependence I built a predicted heat map of the gas within the detector over the course of the flight. This involved calibrating the thermistors based on data collected when the experiment was on the ground. This helped confirm that the predicted temperature was reasonable and that the variation was temperature dependent. This algorithms and this study can now be applied to the full data set to develop a calibration method.

A study on the determination of the metabolites of 2,4,6-Trinitrotoluene using a dual-drift tube ion mobility spectrometer

2,4,6-Trinitrotoluene (TNT) and its four metabolites, namely 2-ADNT, 4-ADNT, 2,4-DANT, and 2,6-DANT, are highly toxic substances. These metabolites also serve as biomarkers for assessing the health of individuals exposed to TNT. In this study, a homemade DDT-IMS apparatus was utilized to detect these metabolites. Under negative detection mode, the drift times of 2-ADNT and 4-ADNT showed subtle shifts within a drift tube temperature range of 100 °C–120 °C, aiding in their differentiation. In positive detection mode for 2,4-DANT and 2,6-DANT, significant variations were observed in both the number and drift time of their positive product ions across a drift tube temperature range of 80 °C–120 °C. Consequently, optimal analytical performance for these metabolites was achieved at approximately 100 °C. Evaluation of the instrumental response during the measurement of the four metabolites in both positive and negative modes revealed that negative detection mode offered greater advantages of detecting these compounds. The working ranges for measuring the four metabolites spanned two orders of magnitude, with detection limits for each metabolite nearly below 1 ng. Notably, clear identification of the signals for these metabolites was achieved even when samples were mixed in urine, highlighting the ability of the DDT-IMS in detecting TNT metabolites. The developed DDT-IMS detection method has significant potential for enhancing environmental risk assessment and biological hazard evaluation, particularly in relation to human exposure to TNT.

Deciphering the Molecular Dance: Exploring the Dynamic Interplay Between Mouse Insulin B9-23 Peptides and their Variants.

Type 1 diabetes results from the autoimmune destruction of pancreatic insulin-producing β-cells, primarily targeted by autoreactive T cells that recognize insulin B9-23 peptides as antigens. Using drift tube ion mobility spectrometry-mass spectrometry, transmission electron microscopy, and two-dimensional infrared spectroscopy, we characterized mouse insulin 1 B9-23 (Ins1 B9-23), insulin 2 B9-23 (Ins2 B9-23), along with two of their mutants, Ins2 B9-23 Y16A and Ins2 B9-23 C19S. Our findings indicate that Ins1 B9-23 and the Ins2 Y16A mutant exhibit rapid fibril formation, whereas Ins2 B9-23 and the Ins2 C19S mutant show slower fibrillization and a structural rearrangement from globular protofibrils to fibrillar aggregates. These differences in aggregation behaviors also manifest in interactions with (-)epigallocatechin gallate (EGCG), a canonical amyloid inhibitor. EGCG effectively disrupts the fibrils formed by Ins1 B9-23 and the Y16A mutant. However, it proves ineffective in preventing fibril formation of Ins2 B9-23 and the C19S mutant. These results establish a strong correlation between the aggregation behaviors of these peptides and their divergent effects on anti-islet autoimmunity.

Measurement of the Cross Section for the Neutron-Induced Fission of 237Np Nuclei in the Energy Range of 0.3–500 MeV

The cross section for the neutron-induced fission of 237Np nuclei in the neutron energy range of 0.3–500 MeV has been measured using the time-of-flight spectrometer of the GNEIS neutron complex at the Petersburg Nuclear Physics Institute, National Research Center Kurchatov Institute. The 237Np(n, f) fission cross section has been measured with respect to the 235U(n, f) fission cross section and fission fragments have been detected by low-pressure position-sensitive multiwire proportional counters. The data obtained have been compared to the previous experimental results and to estimates from various evaluated data libraries.

Construction and performance of the precision tracking chambers for the ATLAS muon spectrometer upgrade for high-luminosity LHC

For the operation at the High-Luminosity (HL) LHC, the Monitored Drift Tube (MDT) chambers of the inner barrel layer (BIS) of the ATLAS muon spectrometer will be replaced by small-diameter Muon Drift Tube (sMDT) chambers which will be integrated with triplets of thin-gap Resistive Plate Chambers (RPC) in order to improve the acceptance and robustness of the barrel muon trigger system. The sMDT chambers have half the drift tube diameter of the MDT chambers and about one order of magnitude higher background rate capability. The construction of the 96 new sMDT chambers was performed between January 2021 and September 2023 at two production sites at a continuous rate of one chamber every two weeks. The sense wire positioning accuracy guaranteed by precision assembly jigs was measured to be around 5μm over the whole construction period. Stringent performance tests had to be passed during the production which have been successfully repeated after delivery of the chambers to CERN. The chambers have been tested with the new MDT front-end ASICs developed for operation at HL-LHC which improve the spatial resolution of the drift tubes by 10% compared to readout with the legacy electronics.

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

Besides safety and security applications, ion mobility spectrometry (IMS) is increasingly used in other fields such as medicine, environmental monitoring and food quality analysis. However, some applications require gas chromatographic separation before analysis by IMS. Furthermore, different compounds in the sample may form positive or negative ions during ionization and therefore simultaneous detection of both ion polarities is highly beneficial to avoid two chromatographic runs of the same sample. This can be achieved by ultra-fast polarity switching of a single drift tube IMS, allowing for quasi-simultaneous detection of both ion polarities. By using a ramped aperture voltage during the switching process, we overcome the issue of excessive displacement currents at the detector during polarity switching, which usually lead to overdriving the output signal of the high-gain transimpedance amplifier. Furthermore, mechanical aperture grid oscillations caused by polarity switching were also reduced through the ramped aperture voltage. This enables a polarity switching time of only 7 ms at a drift voltage of 8 kV and a drift length of 103 mm, leading to a high resolving power of RP = 117. Requiring 50 ms to acquire a pair of positive and negative spectrum, the IMS achieves an acquisition rate of 20 Hz. It reaches limits of detection of 20 pptv for dimethyl methylphosphonate and 40 pptv for methyl salicylate. For demonstration, different hop varieties were investigated and could be clearly differentiated by considering both, the positive and negative spectra.

Alignment of the MEG II cylindrical drift chamber

We present the ongoing development of an algorithm for the software alignment of the MEG II drift chamber based on the MillePede global approach. This method uses cosmic rays data collected during the 2022 data taking period to perform wire-by-wire alignment. We discuss first results obtained on data.

Searching for Centers of Point Emissions on the Cathode of a Multiwire Proportional Chamber via Atomic Force Microscopy

Searching for Centers of Point Emissions on the Cathode of a Multiwire Proportional Chamber via Atomic Force Microscopy

High Resolution Ion Mobility Enables the Structural Characterization of Atropisomers of GDC-6036, a KRAS G12C Covalent Inhibitor.

GDC-6036 is a covalent KRAS G12C inhibitor that demonstrates high potency and selectivity. Structurally, GDC-6036 consists of several motifs that make the analytical characterization of this molecule challenging, including a highly basic pyrrolidine motif bonded to a quinazoline ring via an ether bond and an atropisomeric carbon-carbon bond between functionalized pyridine and quinazoline groups. Structurally, the desired atropisomer was synthesized via an atroposelective Negishi coupling with very high yield. However, having a direct way to analyze and confirm the presence of the atropisomeric species remained challenging in routine analytical workflows. In this study, both variable temperature nuclear magnetic resonance (VT-NMR) and two different approaches of in-line ion mobility coupled to liquid chromatography mass spectrometry (LC-MS) workflows were evaluated for the characterization of GDC-6036 and its undesired atropisomer (Compound B) to support synthetic route development. Briefly, both VT-NMR and traveling wave ion mobility spectrometry (TWIMS) enabled by structures for lossless ion manipulation (SLIM) technology coupled to high resolution MS (HRMS) are able to elucidate the structures of the atropisomers in a complex mixture. Drift tube IMS (DTIMS) was also evaluated, but lacked the resolving power to demonstrate separation between the two species in a mixture, but did show slight differences in their arrival times when multiplexed and injected separately. The determined resolving power (Rp) by multiplexing the ions via DTIMS was 67.3 and 60.5 for GDC-6036 and Compound B, respectively, while the two peak resolving power (Rpp) was determined to be 0.41, indicating inadequate resolution between the two species. Alternatively, the SLIM-IM studies showed Rp of 103.8 and 99.4, with a Rpp of 2.64, indicating good separation between the atropisomers. Furthermore, the CCS/z for GDC-6036 and Compound B was determined to be 231.2 Å2/z and 235.0 Å2/z, respectively. Quantitative experiments demonstrate linearity (R2 >0.99) for both GDC-6036 and Compound B while maintaining separation via SLIM-IM. Spike recoveries of one atropisomer relative to the other yielded strong recoveries (98.7% to 102.5%) while maintaining reproducibility (<7% RSD). The study herein describes the analytical process for evaluating new technologies and strategies for implementation in routine biopharmaceutical characterization workflows.

Accurate Collisional Cross Section Measurement by Multipass Cyclic Ion Mobility Spectrometry.

Ion mobility-mass spectrometry (IM-MS) is a powerful analytical tool for structural characterization. IM measurement provides collision cross section (CCS) values that facilitate analyte identification. While CCS values can be directly calculated from mobility measurements obtained using drift tube ion mobility spectrometry (DT-IMS), this method has limited mobility resolution due to the practical constraints on the length of the ion drift path. Consequently, DT-IMS cannot differentiate analytes with similar mobilities or resolve fine mobility features of individual ions. Cyclic IMS (cIMS) instruments leverage a cyclic path enabled by traveling wave ion mobility (TWIM) technology and offer increased mobility solution to address this challenge. While TWIM devices must first be calibrated to enable CCS measurements, current calibration strategies are primarily tailored for single-pass analyses. This preference is partly attributed to the challenges associated with multipass calibration methods, which require both calibrants and analytes to experience the same number of passes. Achieving this consistency can be complicated due to factors like peak splitting and diffusion, and may not be feasible for online IM-MS analyses. A recent report employed average ion velocities obtained from multiple measurements under different separation pathlengths as a path length-independent metric for CCS calibration. However, the ability to exploit this averaging approach is limited by observed variation in ion drift time/velocity in these measurements. In this study, we introduce a novel calibration strategy designed for multipass cIMS analyses, directly targeting the root cause for the path length- and mobility-dependent variations in ion drift time. With this method, we demonstrate that CCS values derived from multipass measurements closely align with those obtained from single-pass analyses, with an average deviation of 0.1%. We apply this method to characterize four isomeric trisaccharides. Our approach not only results in excellent agreement between our measured cIMSCCS values and the reported DTCCS values, with an average difference of only 0.5%, but also allows us to effectively identify subtle mobility characteristics of each compound and determine their respective CCS values. This level of detail and accuracy was previously unattainable using DT-IMS or single-pass cIMS measurements. We developed an algorithm for reconstructing arrival time distribution in cases where wrap-around has resulted in peak splitting. Collectively, the new calibration strategy and the reconstruction procedure maintain reproducibility and precision in CCS measurements while largely eliminating the need for meticulous selection of separation times. We expect that our method will empower researchers to harness the high mobility resolution offered by multipass cIMS analyses without compromising the accuracy of CCS measurement, making it appropriate for straightforward use across a wide range of applications.

Simulation and reconstruction of particle trajectories in the CEPC drift chamber

The circular electron-positron collider (CEPC) is designed to precisely measure the properties of the Higgs boson, study electroweak interactions at the Z-boson peak, and search for new physics beyond the Standard Model. As a component of the 4th\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$4^{\ ext {th}}$$\\end{document} conceptual CEPC detector, the drift chamber facilitates the measurement of charged particles. This study implemented a Geant4-based simulation and track reconstruction for the drift chamber. For the simulation, detector construction and response were implemented and added to the CEPC simulation chain. The development of track reconstruction involves track finding using the combinatorial Kalman filter method and track fitting using the tool of GenFit. Using the simulated data, the tracking performance was studied. The results showed that both the reconstruction resolution and tracking efficiency satisfied the requirements of the CEPC experiment.