Drift Tube Research Articles

Separation of Isomeric Metabolites and Gangliosides with High Performance (Drift Tube) Ion Mobility–Mass Spectrometry

The study of metabolites and gangliosides is increasingly important in drug discovery (1) and immunology (2). Accurate analysis of biologically relevant isomers is important because their structure affects their molecular properties. Typically, the isomers are separated using chromatography prior to mass spectrometry (MS) analysis. However, specialized chromatographic methods that distinguish isomers frequently require a complex setup and long runs. Techniques that allow accurate results to be acquired quickly and efficiently would be beneficial.

Towards a miniaturized on-site nano-high performance liquid chromatography electrospray ionization ion mobility spectrometer with online enrichment

Safeguarding water quality is resource-intensive and costly. Especially in cases of accidents or disasters, compact devices that allow quick assessment of the current situation are lacking. The objective of this work is the development of a portable measuring device for on-site detection of pollutants in water based on nano-high performance liquid chromatography (nano-HPLC) and electrospray ionization (ESI) ion mobility spectrometry (IMS). Integrated online enrichment by means of solid phase extraction (SPE) further improves sensitivity. In this work, an SPE cartridge exchange unit is presented, which was developed by additive manufacturing in a cost-effective and resource-efficient way. Prerequisites are an easy adaptation to commercially available SPE cartridges and pressure stability of up to 50 bar. In addition, a compact ESI-IMS with 75 mm drift tube length and a resolving power of R = 100 is presented that enables ionization, separation based on ion mobility and detection of analytes at a flow rate of 0.6 – 1.8 µL/min from the liquid phase. This approach also allows miniaturization of the overall system leading to a reduction in energy requirements and the amount of solvents used. For future environmentally benign systems, complete elimination of toxic solvents would be ideal. Therefore, acetonitrile and the nontoxic ethanol are compared as organic mobile phase in terms of elution and ionization efficiency. For characterization, a test mixture containing relevant target analytes, such as chlortoluron, isoproturon, pyrimethanil, mepanipyrim, cyprodinil and carbamazepine, is analyzed. In addition, the analytical greenness metric approach tool is used to evaluate the overall system in terms of its green credentials. It was shown that ethanol can be well used as an organic solvent for the mobile phase and even exhibits better ionization than acetonitrile for the selected model analytes. Furthermore, a relatively high orthogonality of O=0.53 and an effective 2D peak capacity of 2Dneff=174 are reached. Due to the overall miniaturization and splitless coupling, the aims of green chemistry can be met, and ideally a value of 0.92 can be achieved using the AGREE tool for the presented system.

An ion mobility mass spectrometer coupled with a cryogenic ion trap for recording electronic spectra of charged, isomer-selected clusters.

Infrared and electronic spectra are indispensable for understanding the structural and energetic properties of charged molecules and clusters in the gas phase. However, the presence of isomers can potentially complicate the interpretation of spectra, even if the target molecules or clusters are mass-selected beforehand. Here, we describe an instrument for spectroscopically characterizing charged molecular clusters that have been selected according to both their isomeric form and their mass-to-charge ratio. Cluster ions generated by laser ablation of a solid sample are selected according to their collision cross sections with helium buffer gas using a drift tube ion mobility spectrometer and their mass-to-charge ratio using a quadrupole mass filter. The mobility- and mass-selected target ions are introduced into a cryogenically cooled, three-dimensional quadrupole ion trap where they are thermalized through inelastic collisions with an inert buffer gas (He or He/N2 mixture). Spectra of the molecular ions are obtained by tagging them with inert atoms or molecules (Ne and N2), which are dislodged following resonant excitation of an electronic transition, or by photodissociating the cluster itself following absorption of one or more photons. An electronic spectrum is generated by monitoring the charged photofragment yield as a function of wavelength. The capacity of the instrument is illustrated with the resonance-enhanced photodissociation action spectra of carbon clusters (Cn +) and polyacetylene cations (HC2nH+) that have been selected according to the mass-to-charge ratio and collision cross section with He buffer gas and of mass-selected Au2 + and Au2Ag+ clusters.

CANREB EBIS commissioning at TRIUMF

The Canadian Rare Isotope facility with Electron Beam ion source (CANREB) is an essential part of the Advanced Rare IsotopE Laboratory (ARIEL) presently under construction at TRIUMF. CANREB was recently commissioned and can accept stable or rare isotope beams from a variety of ion sources, delivering high purity beams of highly charged ions (HCI) to experiments. The injected beams are bunched using a radiofrequency quadrupole cooler-buncher and energy adjusted using a pulsed drift tube for injection into the electron beam ion source (EBIS) charge state breeder. The EBIS is designed for a maximum electron beam current of 500 mA and a maximum magnetic field of 6 T. Ions with energies up to 14 keV can be injected and HCI with mass-to-charge (A/q) ratios 3 ⩽ A/q ⩽ 7 can be charge bred and extracted. The HCI are A/q-selected using a Nier-type spectrometer before being transported to the ISAC linac for post-acceleration. Results from CANREB beam commissioning with focus on the EBIS will be presented.

A Low Energy H Beamline for the ALPHA Antihydrogen Experiment

The CERN ALPHA experiment makes precision measurements of antihydrogen atoms, confined in a superconducting magnetic minimum trap. Recent measurements of the antihydrogen spectrum have already provided high-resolution tests of fundamental symmetries, and ALPHA has now embarked on an ambitious upgrade programme aimed at directly comparing hydrogen and antihydrogen within their existing atom trap. One aspect of this upgrade will be the development of a low-energy (50 eV) hydrogen ion source that is compatible with ALPHA’s existing magnetic charged particle beamlines. PELLIS, previously developed at JYFL, is a 5 keV filament-driven source that generates H- beams with low emittances and currents of up to 50 μA. Here, we explore the feasibility of a proposed electrostatic beamline design to transport H- ions from a PELLIS-type ion source into ALPHA’s various particle traps. We present SIMION simulations that were used to develop the beamline, focusing on components such as a quadrupole switchyard and drift tube deceleration stage.

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.

Volatilomics-Based Microbiome Evaluation of Fermented Dairy by Prototypic Headspace-Gas Chromatography-High-Temperature Ion Mobility Spectrometry (HS-GC-HTIMS) and Non-Negative Matrix Factorization (NNMF).

Fermented foods, such as yogurt and kefir, contain a versatile spectrum of volatile organic compounds (VOCs), including ethanol, acetic acid, ethyl acetate, and diacetyl. To overcome the challenge of overlapping peaks regarding these key compounds, the drift tube temperature was raised in a prototypic high-temperature ion mobility spectrometer (HTIMS). This HS-GC-HTIMS was used for the volatilomic profiling of 33 traditional kefir, 13 commercial kefir, and 15 commercial yogurt samples. Pattern recognition techniques, including principal component analysis (PCA) and NNMF, in combination with non-targeted screening, revealed distinct differences between traditional and commercial kefir while showing strong similarities between commercial kefir and yogurt. Classification of fermented dairy samples into commercial yogurt, commercial kefir, traditional mild kefir, and traditional tangy kefir was also possible for both PCA- and NNMF-based models, obtaining cross-validation (CV) error rates of 0% for PCA-LDA, PCA-kNN (k = 5), and NNMF-kNN (k = 5) and 3.3% for PCA-SVM and NNMF-LDA. Through back projection of NNMF loadings, characteristic substances were identified, indicating a mild flavor composition of commercial samples, with high concentrations of buttery-flavored diacetyl. In contrast, traditional kefir showed a diverse VOC profile with high amounts of flavorful alcohols (including ethanol and methyl-1-butanol), esters (including ethyl acetate and 3-methylbutyl acetate), and aldehydes. For validation of the results and deeper understanding, qPCR sequencing was used to evaluate the microbial consortia, confirming the microbial associations between commercial kefir and commercial yogurt and reinforcing the differences between traditional and commercial kefir. The diverse flavor profile of traditional kefir primarily results from the yeast consortium, while commercial kefir and yogurt is primarily, but not exclusively, produced through bacterial fermentation. The flavor profile of fermented dairy products may be used to directly evaluate the microbial consortium using HS-GC-HTIMS analysis.

Effect of non-uniform magnetic field on radial oscillation of electron beam in a low-magnetic-field foilless diode

A theory regarding a non-uniform magnetic field with a parallel gradient is presented. The research results show that a proper non-uniform magnetic field can greatly reduce the transverse momentum of an electron beam and even eliminate its gyration motion, and it depends on the gradient of the magnetic field and the phases of electrons entering and leaving the local magnetic field region. Thus, a magnetic field that decreases along the axial direction is proposed to suppress the radial oscillation of the electron beam. However, in the drift tube, the suppression of the radial oscillation is not obvious, because the large phase differences among electrons lead to a mismatch between the electron beam and the non-uniform magnetic field. Further studies found that the non-uniform magnetic field applied in the anode-cathode gap can not only reduce the phase differences among electrons, but also effectively transform the transverse momentum of the electron beam into its axial momentum. The results obtained by PIC simulations and experiments consistently confirm that the non-uniform magnetic field can significantly suppress the radial oscillation of the electron beam in a low-magnetic-field foilless diode.

Using machine learning for particle track identification in the CLAS12 detector

Particle track reconstruction is the most computationally intensive process in nuclear physics experiments. Traditional algorithms use a combinatorial approach that exhaustively tests track measurements (“hits”) to identify those that form an actual particle trajectory. In this article, we describe the development of four machine learning (ML) models that assist the tracking algorithm by identifying valid track candidates from the measurements in drift chambers. Several types of machine learning models were tested, including: Convolutional Neural Networks (CNN), Multi-Layer Perceptrons (MLP), Extremely Randomized Trees (ERT) and Recurrent Neural Networks (RNN). As a result of this work, an MLP network classifier was implemented as part of the CLAS12 reconstruction software to provide the tracking code with recommended track candidates. The resulting software achieved accuracy of greater than 99% and resulted in an end-to-end speedup of 35% compared to existing algorithms.

A 4-Channel Ultra-Low Power Front-End Electronics in 65 nm CMOS for ATLAS MDT Detectors

A 4-channel front-end electronics (4 × FEE) system for the muon drift tube in the ATLAS detector in the High-Luminosity LHC is presented. The overall channel architecture is optimized to reduce the power and area of the design. Each channel comprises a charge-sensitive preamplifier (CSP), shaper, discriminator and differential low-voltage signaling drivers. The proposed channel operates with a 5–100 fC input charge and exhibits a linear sensitivity of 8 mV/fC for the entire input charge range. The peaking time delay of the analog channel is 14.6 ns. At the output, the time representation of the input signal is provided in terms of the CMOS level and in scalable low-voltage signal (SLVS). The FEE consumes a current of 10.6 mA per channel from a single 1.2 V supply voltage. The full 4 × FEE design is realized in TSMC 65 nm CMOS technology and its die-area is 2 mm × 2 mm.

A versatile vacuum ultraviolet ion source for reduced pressure bipolar chemical ionization mass spectrometry

Abstract. We present the development of a chemical ionization mass spectrometer ion source specifically designed for in situ measurements of trace gases in the upper troposphere and lower stratosphere. The ion source utilizes a commercially available photoionization krypton lamp, primarily emitting photons in the vacuum ultraviolet (VUV) region at wavelengths of 124 and 117 nm (corresponding to energies of 10 and 10.6 eV, respectively), coupled to a commercially available Vocus proton transfer reaction mass spectrometer. The VUV ion source can produce both negative and positive reagent ions; however, here we primarily focus on generating iodide anions (I−). The instrument's drift tube (also known as ion–molecule reactor) operates at pressures between 2 and 10 mbar, which facilitates ambient sampling at atmospheric pressures as low as 50 mbar. The low operating pressure reduces secondary ion chemistry that can occur in iodide chemical ionization mass spectrometry (CIMS). It also allows the addition of water vapor to the drift tube to exceed typical ambient humidity by more than 1 order of magnitude, significantly reducing ambient humidity dependence of sensitivities. An additional benefit of this ion source and drift tube is a 10- to 100-fold reduction in nitrogen consumed during operation relative to standard I− ion sources, resulting in significantly reduced instrument weight and operational costs. In iodide mode, sensitivities of 76 cps ppt−1 for nitric acid, 35 cps ppt−1 for Br2 and 8.9 cps ppt−1 for Cl2 were achieved. Lastly, we demonstrate that this ion source can generate benzene (C6H6+) and ammonium (NH4+) reagent ions to expand the number of detected atmospheric trace gases.

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.

AI for Experimental Controls at Jefferson Lab

The AI for Experimental Controls project is developing an AI system to control and calibrate detector systems located at Jefferson Laboratory. Currently, calibrations are performed offline and require significant time and attention from experts. This work would reduce the amount of data and the amount of time spent calibrating in an offline setting. The first use case involves the Central Drift Chamber (CDC) located inside the GlueX spectrometer in Hall D. We use a combination of environmental and experimental data, such as atmospheric pressure, gas temperature, and the flux of incident particles as inputs to a sequential Neural Network (NN) to recommend a high voltage setting and the corresponding calibration constants in order to maintain consistent gain and optimal resolution throughout the experiment. Utilizing AI in this manner represents an initial shift from offline calibration towards near real time calibrations performed at Jefferson Laboratory.

Design and Experiment of a Hollow Beam Electron Optics System for Ka-Band Extended Interaction Klystrons

In this article, the design and experiment of a hollow electron beam (HEB) electron optics system (EOS) for Ka-band extended interaction klystrons (EIKs) are presented. To realize the fast switch of the current emission at a low cutoff voltage, an electron gun with two focus electrodes (FEs) is chosen. The emitting surface of cathode is a ringed spherical surface. The first focus electrode (FE1) is around the cathode, and the second focus electrode (FE2) is set in the central hole of the cathode. The current emitted from the cathode surface is about 2A, when the operating voltage is 25 kV. Three simulation codes, Egun, Superfish, and CST, are used for designing the electron gun and the permanent magnet focusing system (PMFS). Some sensitivity analyses with respect to the PMFS’s critical parameters are presented. The simulation shows the dc beam transmission is 100%. The electron beam, confined by 6000 Gauss uniform field, propagates through the drift tube of 37 mm with good laminarity and small ripple. The emission current can be suppressed when the voltage of the FEs is −3.4 kV. According to the results of simulation, the Ka-band EIK had been constructed and the hot-test experiments had been fulfilled in succession. The experimental results exhibit that the dc beam transmission is about 99% and the beam can sustain 98% transmission at high frequency (HF) operation. In addition, the output power is higher than 8 kW in the bandwidth of over 100 MHz.

Rapid HILIC-Z ion mobility mass spectrometry (RHIMMS) method for untargeted metabolomics of complex biological samples

IntroductionRecent advances in high-throughput methodologies in the ‘omics’ and synthetic biology fields call for rapid and sensitive workflows in the metabolic phenotyping of complex biological samples.ObjectiveThe objective of this research was to evaluate a straightforward to implement LC–MS metabolomics method using a commercially available chromatography column that provides increased throughput. Reducing run time can potentially impact chromatography and therefore the effects of ion mobility spectrometry to expand peak capacity were also evaluated. Additional confidence provided via collision cross section measurements for detected features was also explored.MethodsA rapid untargeted metabolomics workflow was developed with broad metabolome coverage, combining zwitterionic-phase hydrophilic interaction chromatography (HILIC-Z) with drift tube ion mobility-quadrupole time-of-flight (DTIM-qTOF) mass spectrometry. The analytical performance of our method was explored using extracts from complex biological samples, including a reproducibility study on chicken serum and a simple comparative study on a bacterial metabolome.ResultsThe method is acronymised RHIMMS for rapid HILIC-Z ion mobility mass spectrometry. We present the RHIMMS workflow starting with data acquisition, followed by data processing and analysis. RHIMMS demonstrates improved chromatographic separation for a selection of metabolites with wide physicochemical properties while maintaining reproducibility at better than 20% over 200 injections at 3.5 min per sample for the selected metabolites, and a mean of 13.9% for the top 50 metabolites by intensity. Additionally, the combination of rapid chromatographic separation with ion mobility allows improved annotation and the ability to distinguish isobaric compounds.ConclusionOur results demonstrate RHIMMS to be a rapid, reproducible, sensitive and high-resolution analytical platform that is highly applicable to the untargeted metabolomics analysis of complex samples.

Portable nanoelectrospray periodic focusing differential ion mobility spectrometer for the rapid screening of illicit drugs

The spread of illicit drug abuse is a major public health issue in most countries. Law enforcement personnel on drug abuse need a tool to confiscate and block illicit trade of illicit drug or monitoring drug impaired driving. Therefore, affordable and portable instruments for illegal drug detection are in critical need. In this study, we developed a portable periodic focusing differential ion mobility (PFDMA) spectrometer for in situ motoring illicit drugs. The device comprised an ionization source, drift cell, air blower, voltage divider board and electronic control board. In general, an ion mobility spectrometer (IMS) is able to work with air as a buffer gas at atmospheric pressure. There is no need to install heavy mechanical and/or expensive turbo molecular pumps. For our instrument, a small air blower was used to generate laminar counterflow. The whole device is compact with a size of 150 × 200 × 280 (WLH, mm) and a weight of 2.5 kg. In general, most commercial drift tube ion mobility spectrometers use radioactive or corona discharge ionization. In this work, we utilized a different approach to analyze liquid samples. The device was equipped with a nanoelectrospray ionization source. To avoid memory effects, a disposable micropipette was used. An aluminum-coated tip with an ID of 2 μm was applied with a high voltage to achieve nanoelectrospray ionization without sheath gas. Advantages of PFDMA are to isomer separation and better sensitivity compared to other types of ion mobility spectrometers. Most illicit drugs could be detected by this homemade device. The detection limit is lower than the level allowed by law. With our device, the detection limit of methamphetamine is ∼10 ng/ml.

Characterization of compositional variability in petroleum substances

In the process of registration of substances of Unknown or Variable Composition, Complex Reaction Products or Biological Materials (UVCBs), information sufficient to enable substance identification must be provided. Substance identification for UVCBs formed through petroleum refining is particularly challenging due to their chemical complexity, as well as variability in refining process conditions and composition of the feedstocks. This study aimed to characterize compositional variability of petroleum UVCBs both within and across product categories. We utilized ion mobility spectrometry (IMS)-MS as a technique to evaluate detailed chemical composition of independent production cycle-derived samples of 6 petroleum products from 3 manufacturing categories (heavy aromatic, hydrotreated light paraffinic, and hydrotreated heavy paraffinic). Atmospheric pressure photoionization and drift tube IMS-MS were used to identify structurally related compounds and quantify between- and within-product variability. In addition, we determined both individual molecules and hydrocarbon blocks that were most variable in samples from different production cycles. We found that detailed chemical compositional data on petroleum UVCBs obtained from IMS-MS can provide the information necessary for hazard and risk characterization in terms of quantifying the variability of the products in a manufacturing category, as well as in subsequent production cycles of the same product.

Dual-Polarity Ion Drift Chamber: A new system to measure the mobility of positive and negative ions

A new experimental system was recently developed to measure the mobility of both positive and negative ions: the Dual-Polarity Ion Drift Chamber (DP-IDC). In this work, we present a detailed description of the experimental setup and technique used, as well as the initial studies carried out. The reduced ion mobilities of SF5− and SF6− were measured in pure SF6, SF6-CF4 and SF6-N2, for pressures between 10 and 30 Torr and reduced electric fields ranging from 10 to 40 Td. The results were compared with experimental and theoretical data available, and a good performance was found. The study of the mobility of positive ions in Ne-CF4 gas mixtures was also performed, with the results obtained showing a good agreement with those determined in a similar setup previously developed by our group. The importance of this type of studies is also discussed, along with the future prospects for this experimental system.

Electron collisions with dimethylamine and trimethylamine molecules and molecular ions

Experiments are described in which the dissociative recombination of trimethylamine and dimethylamine ions and related product ions, was studied using a Flowing Afterglow Langmuir Probe- Mass Spectrometer (FALP-MS) apparatus. The technique used in this experiment is based on the measurement of the decay of the electron density as an afterglow plasma flows along a drift tube. The results obtained for the DR for dimethylamine and trimethylamine ions were measured using three different methods. The results for trimethylamine ions are in reasonable accord with those for other polyatomic ions while for dimethylamine ions, are unreasonably high and this was explained by the competition from electron capture by neutral dimethylamine molecules.