Drift Tube Research Articles

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.

Investigating the Potential of Drift Tube Ion Mobility for the Analysis of Oxidized Lipids.

Epilipids, a subset of the lipidome that comprises oxidized, nitrated, and halogenated lipid species, show important biochemical activity in the regulation of redox lipid metabolism by influencing cell fate decisions, including death, health, and aging. Due to the large chemical diversity, reversed-phase liquid chromatography-high-resolution mass spectrometry (RPLC-HRMS) methods have only a limited ability to separate numerous isobaric and isomeric epilipids. Ion mobility spectrometry (IMS) is a gas-phase separation technique that can be combined with LC-HRMS to improve the overall peak capacity of the analytical platform. Here, we illustrate the advantages and discuss the current limitations of implementing IMS in LC-HRMS workflows for the analysis of oxylipins and oxidized complex lipids. Using isomeric mixtures of oxylipins, we demonstrated that while deprotonated ions of eicosanoids were poorly resolved by IMS, sodium acetate and metal adducts (e.g., Li, Na, Ag, Ba, K) of structural isomers often showed ΔCCS% above 1.4% and base peak separation with high-resolution demultiplexing (HRDm). The knowledge of the IM migration order was also used as a proof of concept to help in the annotation of oxidized complex lipids using HRDm and all-ion fragmentation spectra. Additionally, we used a mixture of deuterium-labeled lipids for a routine system suitability test with the purpose of improving harmonization and interoperability of IMS data sets in (epi)lipidomics.

Study and design of the coupled cavity with ladder RFQ and IH DTL structure for transportable neutron source

A transportable accelerator-driven neutron source is under development in Xi'an Jiaotong University (X-TANS), aiming at realizing various outdoor applications, such as on-site degradation diagnosis of concrete infrastructures and analysis of raw materials. To downsize the accelerator cavity for X-TANS, we coupled the Ladder RFQ and an Interdigital H-type Drift tube linac (IH-DTL) into a single cavity to combine the strength of the RFQ's efficient bunching efficiency and DTL's high accelerating gradient and to distantly reduce the weight and size of the linac. To achieve electromagnetic resonance between two structures and a high coupling factor, a novel coupled structure was adopted by adjusting the last supporting plate at the exit of RFQ. The mode separation between 0-mode and π-mode was expanded to 7.96 MHz. Consequently, the 15 mA proton beam can be accelerated to 2.5 MeV with a length of 1.73 m and the effective transmission of above 90%. The dissipated cavity power was 96.87 kW with an operation frequency of 200 MHz and a duty factor of 3%. The design concept of the coupled structure and the results of the beam dynamics design, electromagnetic simulation and multi-physics will be comprehensively presented in this paper.

Fast kernel methods for data quality monitoring as a goodness-of-fit test

We propose an accurate and efficient machine learning approach for monitoring particle detectors in real-time. The goal is to assess the compatibility of incoming experimental data with a reference dataset, characterising the data behaviour under normal circumstances, via a likelihood-ratio hypothesis test. The model is based on a modern implementation of kernel methods, nonparametric algorithms that can learn any continuous function given enough data. The resulting approach is efficient and agnostic to the type of anomaly that may be present in the data. Our study demonstrates the effectiveness of this strategy on multivariate data from drift tube chamber muon detectors.

The development and validation of a novel, green, sustainable and eco-friendly HPLC-ELSD method approach for the simultaneous determination of seven artificial sweeteners in various food products: An assessment of the greenness profile of the developed method with an analytical eco-scale, NEMI, GAPI and AGREE

Minimizing the generation of hazardous chemical waste in routine chromatographic separations has become a critical issue. Here, we introduce a totally green, eco-friendly, novel, sensitive, rapid, robust and simple HPLC-ELSD approach for the simultaneous determination of seven artificial sweeteners which are commonly used in various food samples. The mobile phase was totally free from any toxic solvents or additives. Only water and ethanol were used as the best green alternative solvents for each step of the analysis. Separations were carried out on a C18 column (3.5 μm particle size, 150 mm × 4.6 mm id.) by gradient elution using water–ethanol mixture as a mobile phase. The drift tube of ELSD temperature was adjusted to 50 °C and the N2 gas pressure was adjusted to 350 kPa, the Gain value to 7, and the Filter value to 10 on the HPLC-ELSD system. The developed and validated HPLC-ELSD method provided LOD and LOQ in the range of 1.40–2.23 µg mL−1, 4.67–7.43 µg mL−1 respectively, with recoveries between 98.06 and 102.43%. The method precision (RSD) was found to be lower than 1.0%. The applied HPLC-ELSD method permitted the simultaneous determination of seven artificial sweeteners in under fifteen minutes, consuming only 4.3 mL of a green organic solvent (Ethanol). Moreover, the Greenness assessment of the present HPLC-ELSD method was evaluated using NEMI, Analytical Eco-scale, AGREE and GAPI.

Surveying the mugineic acid family: Ion mobility – quadrupole time-of-flight mass spectrometry (IM-QTOFMS) characterization and tandem mass spectrometry (LC-ESI-MS/MS) quantification of all eight naturally occurring phytosiderophores

Phytosiderophores (PS) are root exudates released by grass species (Poaceae) that play a pivotal role in iron (Fe) plant nutrition. A direct determination of PS in biological samples is of paramount importance in understanding micronutrient acquisition mediated by PS. To date, eight plant-born PS have been identified; however, no analytical procedure is currently available to quantify all eight PS simultaneously with high analytical confidence. With access to the full set of PS standards for the first time, we report comprehensive methods to both fully characterize (IM-QTOFMS) and quantify (LC-ESI-MS/MS) all eight naturally occurring PS belonging to the mugineic acid family. The quantitative method was fully validated, yielding linear results for all eight analytes, and no unwanted interferences with soil and plant matrices were observed. LOD and LOQ values determined for each PS were below 11 and 35 nmol L−1, respectively. The method's precision under reproducibility conditions (intra- and inter-day) of measurement was less than 2.5% RSD for all analytes. Additionally, all PS were annotated with high-resolution mass spectrometric fragment spectra and further characterized via drift tube ion mobility-mass spectrometry. The collision cross-sections obtained for primary ion species yielded a valuable database for future research focused on in-depth PS studies. The new quantitative method was applied to analyse root exudates from Fe-controlled and deficient barley, oat, rye, and sorghum plants. All eight PS, including mugineic acid (MA), 3"-hydroxymugineic acid (HMA), 3"-epi-hydroxymugineic acid (epi-HMA), hydroxyavenic acid (HAVA), deoxymugineic acid (DMA), 3"-hydroxydeoxymugineic acid (HDMA), 3"-epi-hydroxydeoxymugineic acid (epi-HDMA) and avenic acid (AVA) were for the first time successfully identified and quantified in root exudates of various graminaceous plants using a single analytical procedure. These newly developed methods can be applied to studies aimed at improving crop yield and micronutrient grain content for food consumption via plant-based biofortification.

Additive Manufacturing of an IH-Type Linac Structure from Stainless Steel and Pure Copper

Additive manufacturing (AM) of metals has the potential to provide significant benefits for the construction of future particle accelerators. The combination of low cost manufacturing of complex geometries in combination with efficiency gains from improved linac design enabled by AM may be one way towards future cost-effective green accelerator facilities. As a proof of concept, we present a high-efficiency Zeff=280 MΩ/m, 433.632 MHz IH-DTL cavity based on an AM design. In this case, the complex internal drift tube structures with internal cooling channels have been produced from 1.4404 stainless steel and from pure copper using AM. The prototype cavity, as well as stainless steel AM parts have been electroplated with copper. We present results from successful vacuum tests, low level RF measurements of the cavity, as well as the status of preparations for high-power RF tests with a 30 kW pulsed power amplifier.

Debugging the FUMILIM minimization package

The suggested package FUMILIM, based on famous FUMILI minimization package, has the following advantages.Unlimited number of parameters (multi-set tasks).Ability to work with multidimensional experimental points, described by a vector function.The preliminary scan is envisaged for complicated tasks.For heavy user's functions the parallel fit is envisaged with the help of OpenMP service.Multi-optional user interface, including the option to ignore wrong experimental points.The package contains popular intrinsic user's functions. All of them can be used without the definition of the parameter initial values.There is a package of fast track reconstruction programs for working with detectors, including drift chambers. The capacity of these programs is about of 106 tracks per second (at 2.8 GHz).In the corrected version a number of bugs is fixed.The service for multi-set tasks has been essentially expanded.Information support of poorly converged tasks and removing of wrong experimental points is expanded.All programs are written in FORTRAN-90. New version program summaryProgram Title: FUMILIM v4CPC Library link to program files:https://doi.org/10.17632/xphc8ctxr3.3Licensing provisions: GPLv3Programming language: Fortran-90Journal reference of previous version: Comput. Phys. Commun. 251 (2020) 107202Does the new version supersede the previous version?: Yes.Reasons for the new version: To extend the class of solvable tasks, fixing a number of bugs.Summary of revisions:• A number of bugs is fixed.• The service for multi-set tasks has been essentially expanded.• Information support of poorly converged task and removing WP is expanded.• Fast programs are accelerated by ≃15%.• Organization of output options is slightly revised, which provided better comfort for users.• Settings of the package through the redefinition of numbers in common-blocks are replaced by calls to short subroutines. This makes the main program more compact. The old way of setting still works.Nature of problem: To minimize χ2-functional.Solution method: Least square method.

Simulation and validation studies of a large drift tube muon tracker.

Cosmic ray muons are massive, charged particles created from high energy cosmic rays colliding with atomic nuclei in Earth's atmosphere. Because of their high momenta and weak interaction, these muons can penetrate through large thicknesses of dense material before being absorbed, making them ideal for nondestructive imaging of objects composed of high-Z elements. A Giant Muon Tracker with two horizontal 8 × 6 in.2 and two vertical 6 × 6 in.2 modules of drift tubes was used to measure muon tracks passing through samples placed inside the detector volume. The experimental results were used to validate a Monte Carlo simulation of the Giant Muon Tracker. The imaging results of simulated samples were reconstructed and compared with those from the experiment, which showed excellent agreement.

High-Energy Part of the Accelerator for the DARIA Compact Neutron Source: Drift Tube Linac

High-Energy Part of the Accelerator for the DARIA Compact Neutron Source: Drift Tube Linac

Publisher’s Note: “Simulation and validation studies of a large drift tube muon tracker” [Rev. Sci. Instrum. 94, 083301 (2023)

Publisher’s Note: “Simulation and validation studies of a large drift tube muon tracker” [Rev. Sci. Instrum. 94, 083301 (2023)

Measured and projected beam backgrounds in the Belle II experiment at the SuperKEKB collider

The Belle II experiment at the SuperKEKB electron–positron collider aims to collect an unprecedented data set of 50ab−1 to study CP-violation in the B-meson system and to search for Physics beyond the Standard Model. SuperKEKB is already the world’s highest-luminosity collider. In order to collect the planned data set within approximately one decade, the target is to reach a peak luminosity of 6 × 1035cm−2s−1 by further increasing the beam currents and reducing the beam size at the interaction point by squeezing the betatron function down to βy∗=0.3mm. To ensure detector longevity and maintain good reconstruction performance, beam backgrounds must remain well controlled. We report on current background rates in Belle II and compare these against simulation. We find that a number of recent refinements have significantly improved the background simulation accuracy. Finally, we estimate the safety margins going forward. We predict that backgrounds should remain high but acceptable until a luminosity of at least 2.8 × 1035cm−2s−1 is reached for βy∗=0.6mm. At this point, the most vulnerable Belle II detectors, the Time-of-Propagation (TOP) particle identification system and the Central Drift Chamber (CDC), have predicted background hit rates from single-beam and luminosity backgrounds that add up to approximately half of the maximum acceptable rates.

Improved separation of fentanyl isomers using metal cation adducts and high-resolution ion mobility-mass spectrometry.

Fentanyl is a potent synthetic opioid that has attracted significant attention due to its illegal production and distribution, resulting in misuse, overdose, and fatalities. Because numerous fentanyl analogs, including structural isomers, with different potency have been discovered in the field, there is a critical need to continue developing analytical methodologies capable of accurate identification in forensic and clinical laboratories. This study aimed to develop a rapid method for detecting and separating fentanyl isomers based on ion mobility-mass spectrometry (IM-MS), where IM separates gas-phase ions based on differences in their size, shape, and charge. Several strategies for improved differentiation were implemented, including using unconventional cation adducts (e.g., alkali and transition metals) and data post-processing by high-resolution demultiplexing. A collection of collision cross section (CCS) values for the various metal ion adducts was gathered, which can be used to improve confidence of identification in future samples. Notable examples, such as [M + Cu]+ and [M + Ag]+ adducts, contributed to significant improvement of resolution between isomers. Furthermore, the addition of high-resolution post-processing provided resolving power of >150, which constitutes a significant increase in comparison with the normal 50-60 obtained with low-resolution drift tube instruments. Collectively, these improved separation strategies allowed for confident detection and subsequent quantitative analysis. The optimized IM-MS method resulted in quantification of fentanyl in human urine with limits of detection and quantification of 13 pg/mL and 40 pg/mL, respectively.

Determination of Organic Acids in Cucumber Leaves by Solid Phase Extraction–Electrospray Ionization–Ion Mobility Spectrometry (SPE-ESI-IMS)

A solid phase extraction-electrospray ionization-ion mobility spectrometry (SPE-ESI-IMS) method was developed to determine six organic acids in cucumber leaves. The multiplexing IMS using correlation technique was adopted to optimize the signal-to-noise ratio (SNR) and resolution. 90% methanol/water was selected to be the solvent, the flow rate was 120 µL·h−1, the stop frequency of ion gate was 5000 Hz, the ion gate opening period was 0.1 ms, the air flow velocity was 2.0 L·min−1, the electrospray voltage was 3.5 kV, and the drift tube temperature was 90 °C. The cucumber leaves were treated with ultrasound in 50% methanol/water. The analytes were subsequently eluted from an SPE cartridge with 0.1 mol·L−1 HCl, and the extract was neutralized to pH 2–3 with ammonia before freeze-drying. SPE-ESI-IMS enabled the effective determination of citric acid, fumaric acid, lactic acid, malic acid, pyruvic acid, and succinic acid based upon the drift time. The limits of detection were from 0.008 µg·mL−1 to 0.2 µg·mL−1, and the recoveries of spiked samples were from 87.00% to 107.20%. The convenient, sensitive, and efficient developed SPE-ESI-IMS method may be applicable for the determination of organic acids in leaves.

First Measurement of the Michel Parameter ξ^{'} in the τ^{-}→μ^{-}ν[over ¯]_{μ}ν_{τ} Decay at Belle.

We report the first measurement of the Michel parameter ξ^{'} in the τ^{-}→μ^{-}ν[over ¯]_{μ}ν_{τ} decay with a new method proposed just recently. The measurement is based on the reconstruction of the τ^{-}→μ^{-}ν[over ¯]_{μ}ν_{τ} events with subsequent muon decay in flight in the Belle central drift chamber. The analyzed data sample of 988 fb^{-1} collected by the Belle detector corresponds to approximately 912×10^{6} τ^{+}τ^{-} pairs. We measure ξ^{'}=0.22±0.94(stat)±0.42(syst), which is in agreement with the standard model prediction of ξ^{'}=1. Statistical uncertainty dominates in this study, being a limiting factor, while systematic uncertainty is well under control. Our analysis proved the practicability of this promising method and its prospects for further precise measurement in future experiments.

Bond dissociation energies for Fe2+, Fe2O+, and Fe2O2+ clusters determined through threshold photodissociation in a cryogenic ion trap.

Understanding and controlling the chemical behavior of iron and iron oxide clusters requires accurate thermochemical data, which, because of the complex electronic structure of transition metal clusters, can be difficult to calculate reliably. Here, dissociation energies for Fe2+, Fe2O+, and Fe2O2+ are measured using resonance enhanced photodissociation of clusters contained in a cryogenically cooled ion trap. The photodissociation action spectrum of each species exhibits an abrupt onset for the production of Fe+ photofragments from which bond dissociation energies are deduced for Fe2+ (2.529 ± 0.006eV), Fe2O+ (3.503 ± 0.006eV), and Fe2O2+ (4.104 ± 0.006eV). Using previously measured ionization potentials and electron affinities for Fe and Fe2, bond dissociation energies are determined for Fe2 (0.93 ± 0.01eV) and Fe2- (1.68 ± 0.01eV). Measured dissociation energies are used to derive heats of formation ΔfH0(Fe2+) = 1344 ± 2 kJ/mol, ΔfH0(Fe2) = 737 ± 2 kJ/mol, ΔfH0(Fe2-) = 649 ± 2 kJ/mol, ΔfH0(Fe2O+) = 1094 ± 2 kJ/mol, and ΔfH0(Fe2O2+) = 853 ± 21 kJ/mol. The Fe2O2+ ions studied here are determined to have a ring structure based on drift tube ion mobility measurements prior to their confinement in the cryogenic ion trap. The photodissociation measurements significantly improve the accuracy of basic thermochemical data for these small, fundamental iron and iron oxide clusters.

Electrospray Ion Mobility Spectrometer Based on Flexible Printed-Circuit Board Electrodes with Improved Resolving Power.

An easily built drift tube instrument with ring electrodes made of rolled-up flexible printed circuit boards is reported. Its resolving power was maximized by careful attention to the drift tube geometry and the response time of the detector amplifier and by employing a high separation field strength. The separation of singly charged aliphatic quaternary ammonium ions introduced by electrospray was performed, and the measured resolving power was between 86 and 97% of the theoretical limit for three different drift tube lengths investigated. For the longest drift length of 30 cm, a resolving power of up to 228 was obtained. Three benzalkonium chlorides were also separated with resolving powers of over 210. The tristate injection scheme can also be used, with only a small loss of the separation performance compared to the two-state injection.

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.

Multiparticle events in cosmic rays registered by means of drift chambers

Results of the analysis of multiparticle events in cosmic rays in coordinate-tracking setups on the drift chambers CTUDC and ProtoTREK are presented. The analysis of the ProtoTREK data show that it is possible to reconstruct events with a density of up to 15 particles per square meter. The estimation of the energies of primary cosmic rays responsible for the generation of muon bundles detected in the CTUDC was made.

Implementation of ACTS for STCF track reconstruction

With an electron-positron collider operating at center-of-mass-energy 2–7 GeV and a peak luminosity above 0.5 × 1035 cm-2 s-1, the STCF physics program will provide an unique platform for in-depth studies of hadron structure and non-perturbative strong interaction as well as probing new physics beyond the Standard Model in the τ-Charm sector, succeeding the present Beijing Electron-Positron Collider. To fulfill the physics targets and further maximize the physics potential at STCF, the STCF tracking software should have capability to reconstruct charged particles with high efficiency and excellent momentum resolution, especially for the charged particles with low transverse momentum down to 50 MeV. A Common Tracking Software (ACTS) providing a set of detector-independent tracking algorithms is adopted for reconstructing charged tracks with the information of two sub-detectors, a μRWELL-based inner tracker and a drift chamber, at STCF. This is the first demonstration of ACTS for a drift chamber. The implementation details and performance of track reconstruction are presented.