Linear Ion Trap Mass Analyzer Research Articles

Concept and simulation of a novel dual-layer linear ion trap mass analyzer for micro-electromechanical systems mass spectrometry.

This paper proposed a dual-layer linear ion trap mass analyzer (dLIT) based on micro-electromechanical systems (MEMS) technology and stacked-layer structure for the development of MEMS mass spectrometry. Its basic performance and potential capabilities were explored by ion trajectory simulations. The theoretical formulas were modified by implementing multipole expansion. The simulation results were confirmed to be highly consistent with theoretical calculations in multiple aspects, including stability diagram, secular frequencies, and mass linearity, with only a deviation of 1-2%. In the boundary ejection mode, close to 100% ejection was achieved in a single dimension by applying extra quadrupole DC voltage. Preliminary simulation results showed that dLIT can achieve a peak width of ∼2 mass units (full width at half maximum, FWHM) for m/z 60 ions even at pressures as high as 50 Pa. Furthermore, the application of AC frequency scanning mode in dLIT was also evaluated, and preliminary simulation results yield a peak width of 0.3-0.4 mass units (FWHM). The dLIT offered several advantages, including high-precision fabrication at the sub-millimeter scale, excellent high-pressure performance, and a clear physical model. It preliminarily proved to be an ideal mass analyzer for MEMS mass spectrometry.

Linear Ion Trap Mass Spectrometer (LITMS) Instrument Field and Laboratory Tests as Part of the ARADS Field Campaigns.

The highly compact Linear Ion Trap Mass Spectrometer (LITMS), developed at NASA Goddard Space Flight Center, combines Mars-ambient laser desorption-mass spectrometry (LD-MS) and pyrolysis-gas chromatography-mass spectrometry (GC-MS) through a single, miniaturized linear ion trap mass analyzer. The LITMS instrument is based on the Mars Organic Molecule Analyser (MOMA) investigation developed for the European Space Agency's ExoMars Rover Mission with further enhanced analytical features such as dual polarity ion detection and a dual frequency RF (radio frequency) power supply allowing for an increased mass range. The LITMS brassboard prototype underwent an extensive repackaging effort to produce a highly compact system for terrestrial field testing, allowing for molecular sample analysis in rugged planetary analog environments outside the laboratory. The LITMS instrument was successfully field tested in the Mars analog environment of the Atacama Desert in 2019 as part of the Atacama Rover Astrobiology Drilling Studies (ARADS) project, providing the first in situ planetary analog analysis for a high-fidelity, flight-like ion trap mass spectrometer. LITMS continued to serve as a laboratory tool for continued analysis of natural Atacama samples provided by the subsequent 2019 ARADS final field campaign.

Simulation of double resonant excitation of ions in an asymmetric linear ion trap mass analyzer.

Improving the analytical performance of linear ion traps (LITs) is crucial for the advancement of high-performance LIT mass spectrometers. In this study, a double resonant excitation method was employed in an asymmetric LIT to achieve high ion unidirectional ejection efficiency and enhanced mass resolution. The asymmetric trapping field was generated by stretching one x electrode with a distance α. The double resonant excitation was achieved by applying an alternating voltage out of phase and a supplementary alternating voltage in phase to the x and y electrode pairs of the LIT, respectively. Numerical simulations of ion trajectories were performed to validate the effectiveness of this method. The mass resolution of the asymmetric LIT with double resonant excitation could be improved to ~3800, which was over two times compared to that with only dipolar resonant excitation, while both reached ~90% in ion unidirectional ejection efficiency. By employing the double resonant excitation method, the mass resolution could be improved significantly in the asymmetric LIT, while maintaining a considerably high ion unidirectional ejection efficiency. This method might provide a general solution for enhancing ion detection efficiency and mass resolution of LIT mass spectrometers.

Development of a linear ion trap mass spectrometer capable of analyzing megadalton MALDI ions

Detecting megadalton matrix-assisted laser desorption/ionization (MALDI) ions in an ion trap mass spectrometer is a technical challenge. In this study, megadalton protein and polymer ions were successfully measured by MALDI linear ion trap mass spectrometer (LIT-MS) for the first time. The LIT-MS is comprised of a Thermo linear ion trap mass analyzer and a highly sensitive charge-sensing particle detector (CSPD). A newly designed radio frequency (rf) scan mode with dipolar resonance ejection techniques is proposed to extend the mass range of LIT-MS up to one million Thomson (Th). We analyze high mass ions with mass-to charge (m/z) ratios ranging from 100 kTh to 1 MTh, including thyroglobulin, alpha-2-macroglobulin, immunoglobulins (e.g., IgG and IgM), and polymer (∼ 940 kTh) ions. Besides, it is also very challenging for ion trap mass spectrometry to detect megadalton ions at low concentrations. By adopting high affinity carboxylated/oxidized detonation nanodiamonds (oxDNDs) to enrich IgM molecules and form antibody-nanodiamond conjugates, we have successfully reached ∼ 5 nM (5 μg/mL) concentration which is better than that by the other techniques.

High Sensitivity Limited Material Proteomics Empowered by Data-Independent Acquisition on Linear Ion Traps.

In recent years, the concept of cell heterogeneity in biology has gained increasing attention, concomitant with a push toward technologies capable of resolving such biological complexity at the molecular level. For single-cell proteomics using Mass Spectrometry (scMS) and low-input proteomics experiments, the sensitivity of an orbitrap mass analyzer can sometimes be limiting. Therefore, low-input proteomics and scMS could benefit from linear ion traps, which provide faster scanning speeds and higher sensitivity than an orbitrap mass analyzer, however at the cost of resolution. We optimized an acquisition method that combines the orbitrap and linear ion trap, as implemented on a tribrid instrument, while taking advantage of the high-field asymmetric waveform ion mobility spectrometry (FAIMS) pro interface, with a prime focus on low-input applications. First, we compared the performance of orbitrap- versus linear ion trap mass analyzers. Subsequently, we optimized critical method parameters for low-input measurement by data-independent acquisition on the linear ion trap mass analyzer. We conclude that linear ion traps mass analyzers combined with FAIMS and Whisper flow chromatography are well-tailored for low-input proteomics experiments, and can simultaneously increase the throughput and sensitivity of large-scale proteomics experiments where limited material is available, such as clinical samples and cellular subpopulations.

Two-Dimensional Partial Covariance Mass Spectrometry for the Top-Down Analysis of Intact Proteins.

Two-dimensional partial covariance mass spectrometry (2D-PC-MS) exploits the inherent fluctuations of fragment ion abundances across a series of tandem mass spectra, to identify correlated pairs of fragment ions produced along the same fragmentation pathway of the same parent (e.g., peptide) ion. Here, we apply 2D-PC-MS to the analysis of intact protein ions in a standard linear ion trap mass analyzer, using the fact that the fragment-fragment correlation signals are much more specific to the biomolecular sequence than one-dimensional (1D) tandem mass spectrometry (MS/MS) signals at the same mass accuracy and resolution. We show that from the distribution of signals on a 2D-PC-MS map it is possible to extract the charge state of both parent and fragment ions without resolving the isotopic envelope. Furthermore, the 2D map of fragment-fragment correlations naturally separates the products of the primary decomposition pathways of the molecular ions from those of the secondary ones. We access this spectral information using an adapted version of the Hough transform. We demonstrate the successful identification of highly charged, intact protein molecules bypassing the need for high mass resolution. Using this technique, we also perform the in silico deconvolution of the overlapping fragment ion signals from two co-isolated and co-fragmented intact proteins, demonstrating a viable new method for the concurrent mass spectrometric identification of a mixture of intact protein ions from the same fragment ion spectrum.

Investigation of the effect of an octopole electric field on a linear ion trap and an asymmetric semi-circular linear ion trap analyzer.

Linear ion trap mass analyzer could improve analytical performance compared to the traditional three-dimensional ion trap. In this study, a systematic investigation of the effect of octopole field on the performance of linear quadrupole ion trap was studied by both theoretical simulations and experiments. An asymmetric semi-circular linear ion trap (AsC-LIT) analyzer was designed and tested based on the theoretical results. The AsC-LIT consists of one pair of larger semi-circular rods with radius Ry and one pair of smaller semi-circular rods with radius Rx (Ry > Rx) in the cross section for introducing the quantitative octopole field. The analytical performances of these simplified AsC-LITs with different amounts of octopole fields were carefully investigated using both theoretical simulations and experimental validation. Experimental results showed that it could have a mass resolution of 1645 at m/z 175 (arginine); furthermore, the low mass cutoff and CID efficiency can be significantly improved when some positive octopole is added. The simulative results indicated that 2.56% octopole component was the best choice for achieving higher analytical performances. The theoretical and experimental studies of this work could certainly enrich the knowledge of a higher order electric field effect on the linear ion trap, furthermore, the simple geometric design and performance characteristics of this new AsC-LIT make it particularly attractive in the development of miniaturized mass spectrometers.

Ambient Lipidomic Analysis of Single Mammalian Oocytes and Preimplantation Embryos Using Desorption Electrospray Ionization (DESI) Mass Spectrometry.

Desorption electrospray ionization (DESI) is a spray-based ambient ionization method for mass spectrometry (MS) that generates ions in native atmospheric conditions (e.g., pressure and temperature). Ambient ionization allows in situ analysis of unmodified samples by eliminating analyte extraction and separation steps before MS. Lipid analysis of individual mammalian oocytes and preimplantation embryos is challenging because of their complex chemical composition and minute dimensions (100-300μm in diameter). Nonetheless, DESI-MS can provide comprehensive lipidomic profiles of individual oocytes or embryos using a fast and simple workflow. DESI-MS lipid profiles include many classes of lipids such as phosphatidylcholines (PC), triacylglycerols (TAG), free fatty acids (FFA), phosphatidylethanolamines (PE), phosphatidylinositols (PI), phosphatidylserines (PS), diacylglycerols (DAG), ubiquinone, cholesterol and cholesterol derivatives (e.g., cholesterol sulfate and cholesterol esters). Depending on the mass spectrometer used, there is the additional possibility of obtaining structural information of lipids via MSn, and molecular formulae via high resolution MS. Here, we describe the procedures for sample handling, the DESI-MS experimental arrangement, and the data collection and data analysis using low and high-resolution mass spectrometers (such as a linear ion trap and Orbitrap mass analyzer, respectively), as well as strategies for structural characterization of lipids. Lastly, we detail our workflow for relating the chemical information obtained by DESI-MS into the biological context of oocyte and embryo metabolism.

Pseudo-Multiple Reaction Monitoring (Pseudo-MRM) Mode on the "Brick" Mass Spectrometer, Using the Grid-SWIFT Waveform.

Besides portability and increasingly improved performances, the ability of screening target analyte from complex compounds is a crucial function of miniature mass spectrometers, especially for in situ analysis. Selected reaction monitoring (SRM) and multiple reaction monitoring (MRM) operation modes are the most widely used mass spectrometry operation methods for target analyte quantitation. As a continuous effort to improve the analytical performances of the "brick" mass spectrometer, built in-house, pseudo-SRM and pseudo-MRM modes were realized on the linear ion trap mass analyzer in the device. A broadband excitation waveform in both time and frequency domains, namely, the Grid-SWIFT waveform, was constructed and compared with the conventional SWIFT waveform. By isolating target ions during the ion introduction period using the Grid-SWIFT waveform, target ions could be efficiently accumulated inside the ion trap without experiencing space charge effects and interferences from nontarget ions in the samples. As a result, not only the detection sensitivity of the target analyte could be increased, but also the quantitation accuracy over a relatively wide concentration range could be improved.

Simulation of Unidirectional Ion Ejection in an Asymmetric Half-Round Rod Electrode Linear Ion Trap Mass Analyzer.

An asymmetric trapping field was generated from an asymmetric half-round rod electrode linear ion trap (A-HreLIT), and its performance of unidirectional ion ejection was studied. Two different asymmetric structures of A-HreLITs were constructed, one rotating y electrode pairs toward an x electrode with an angle θ, and the other stretching one x electrode with a distance α. The center of trapping field was displaced away from the geometrical center of the ion trap, defined to be the midpoint along the axis of y between x electrodes, which leads to unidirectional ion ejection through one x electrode. Computer simulations were used to investigate the relationship between asymmetric geometric parameter of θ (or α) and analytical performance. Both structures could result in similar asymmetric trapping fields, which mainly composed of dipole, quadrupole, and hexapole fields. The dipole and hexapole fields were approximately proportional to the asymmetric geometric parameter of rotation angle θ (or stretch distance α). In simulation, ion trajectories and ion kinetic energy were calculated. For ions with m/z 609Th, the simulation results showed that mass resolution of over 2400 (FWHM) and ion unidirectional ejection efficiency of nearly 90% were achieved in an optimized A-HreLIT. Ion detection efficiency of A-HreLIT could be improved significantly with only one ion detector, while maintaining a considerable mass resolution. Furthermore, the A-HreLIT could be driven by a traditional balanced RF power supply. These advantages make A-HreLIT suitable for developing miniaturized mass spectrometer with high performance. Graphical Abstract ᅟ.

Optimization of Linear Ion Trap Mass Analyzer with Triangular Electrodes by Simulation

Abstract As a novel linear ion trap, the triangular-electrode linear ion trap (TeLIT) has simple structure and good analysis capacity. To enhance the analysis capacity of TeLIT, the relationship between its geometry and performance was investigated, and the ion trajectories and mass peaks of TeLIT with different ratio of field radius (rx/ry) was analyzed using simulation software SIMION and AXSIM. The results showed that the analytical performance of the TeLIT could be enhanced by optimizing rx/ry to improve the internal electric fields distribution. As a result, the optimum mass resolution of the ion with m/z 1892 Th could reach 8387 when rx/ry = 5.75/5 and scan rate was 1500 Th s−1. Meanwhile, the resolution of the mass spectrum was in excess of 23000 when the scan rate was decreased to about 300 Th s−1.

Structure and Property of Ladder Electrode Linear Ion Trap Mass Analyzer

Abstract The theoretical simulation and optimization of a new linear ion trap mass analyzer-ladder electrode ion trap mass analyzer (LeLIT) was described. The LeLIT was consisted of two pairs of ladder electrodes and one pair of end-electrodes. Compared with conventional rectilinear ion trap (ReLIT) which is built with plate electrodes, LeLIT can adjust and optimize the electric field distribution to obtain optimal performance. Meanwhile, the structure of LeLIT is more similar to the geometrical structure of hyperbolic electrode than that of ReLIT, but it is much easier for processing compared with hyperbolic electrode. According to the simulation results, the optimization of electric field distribution inside the ion trap could be realized through adjusting its geometric parameters such as height, width and field radius ratio of ladder electrodes, which was expected to further optimize the mass spectrometry performance of ion trap. As indicated by theoretical simulation results, mass resolution of 10150 at the scanning speed of 225 Da s−1 was obtained with a LeLIT (dimension of X0 × Y0 = 9 mm × 5 mm). LeLIT can significantly improve the mass resolution while maintaining its simple structure. As indicated by the preliminary experiment results, LeLIT has a good analyzing performance as tandem mass spectrometry.

Real Time Online Correction of Mass Shifts and Intensity Fluctuations in Extractive Electrospray Ionization Mass Spectrometry.

Real time online calibration of mass shift and intensity fluctuation to improve the accuracy of measurements for identification and quantitation in trace mass spectrometric analysis was demonstrated using extractive electrospray ionization mass spectrometry (EESI-MS). The signals of authentic compounds (e.g., lysine (Lys), proline (Pro), and histidine (His)) spiked into the extractive solution for the EESI process were used as the references to calibrate the signal of analytes (e.g., methionine (Met)) in the untreated sample solution. The intensity of the analyte signal was recorded simultaneously with the reference signals. The analyte signals at a given time point were calibrated on the basis of these correlation factors and real time signal response of the reference. The calibrated signal of Met at 10 μg L(-1) was improved with a better signal-to-noise ratio (S/N from 2.3 to 4.3), better linearity (R(2) from 0.9758 to 0.9980), and reduced relative standard deviation (RSD from 9.8% to 6.0%). The shift of mass-to-charge ratio of Met signal between the detected and theoretical values was decreased from 247 ± 133 to -7 ± 167 ppm for 50 min of detection using a linear ion trap mass analyzer and was reduced from -0.27 ± 0.60 to -0.12 ± 0.23 ppm for 50 min of detection using an Orbitrap mass analyzer (P = 95%). This method has been validated using a certified standard amino acids solution (GBW(E)100062) and applied for quantitative detection of amino acids in chicken feed, urine, nutritional drink, and facial mask samples, showing that the method is useful to improve the accuracy of mass spectrometric analysis.

Design and performance evaluation of a linear ion trap mass analyzer featuring half round rod electrodes.

A novel linear ion trap mass analyzer featuring half round rod electrodes (HreLIT) has been built. It is mainly composed of two pairs of stainless steel electrodes which have a cross-section of half round rod and a pair of end electrodes. The HreLIT has a simple structure and so it could be assembled by hand with relatively high mechanical accuracy. The external dimension of HreLIT is 50mm × 29.5mm × 28mm (length × width × height) and its internal volume is about 3.8cm(3). A home-made HreLIT mass spectrometer with three-stage vacuum system was built and the performance of HreLIT was characterized using reserpine solution and PPG standard solution. When the scan rate was 254u/s, mass peak with FWHM of 0.14u was achieved for ions with m/z 609, which corresponds to a mass resolution of 4350. The HreLIT was also operated at a low q value of 0.28 to extend its mass range. The experiment result showed a mass range of over 2800u and the amplitude of radio frequency (rf) signal was only 1560V (0-p). Three-stage tandem mass spectrometry was successfully performed in the HreLIT, and the collision-induced dissociation (CID) efficiencies of MS(2) (CID of ions with m/z 609) and MS(3) (CID of ions with m/z 448) were 78% and 59%, respectively.

Novel linear ion trap mass analyzer built with triangular electrodes.

A novel linear ion trap mass analyzer built with four triangular electrodes, the triangular-electrode linear ion trap (TeLIT), has been built and its performance has been characterized. The TeLIT has all the properties of a conventional LIT mass analyzer, performing ion trapping, mass analysis, and tandem mass spectrometry functions. The TeLIT was constructed with four identical triangular cross-section shaped electrodes and two planar electrodes. Unlike commercial LITs, which have very well-defined hyperbolic shaped electrodes, the TeLIT electrodes have a much simpler geometric structure and larger mechanical tolerances. The electric field distribution inside the IT region was simulated and there are more quadrupole field components and less higher order fields compared with those in other simplified ITs, such as cylindrical ion trap and rectilinear ion trap; hence, the instrument would potentially offer a relatively high mass resolution. In routine measurement, mass analysis with a resolving power of over 1500 at m/z = 609 Th was obtained. The TeLIT was shown to perform basic mass spectrometer functions such as mass-selected isolation, mass-selected ejection and collision-induced dissociation (CID) of ions comparable to other available LITs. Moreover, given the small size of the TeLIT and its simple structure and good analytical performance, further miniaturization and use as a portable mass spectrometer are envisaged.

Optimized DLP linear ion trap for a portable non-scanning mass spectrometer

This work reports implementation of an optimized linear ion trap (LIT) mass analyzer manufactured using digital light processing (DLP), a low cost rapid prototyping technique. To satisfy requirements for a portable commercial instrument, our previous DLP LIT has been improved by using polymer material for electrodes and housing with higher heat deflection temperature and much improved metal coating of the electrodes. In this way, a polymer-based LIT can operate at higher pressures with more stable voltages, low outgassing and with much longer electrode lifetime. This paper demonstrates non-scanning operation of a DLP LIT based on ceramic resin with specially electroplated electrodes. Non-scanning mode is suitable for applications in which only specific mass fragments are targeted such as security and forensics. Experimental results from a DLP LIT are therefore shown for simulants of cocaine, TNT and sarin.

Lipidomic analysis of polyunsaturated fatty acids and their oxygenated metabolites in plasma by solid-phase extraction followed by LC-MS

The present work describes the development of a robust and sensitive targeted analysis platform for the simultaneous quantification in blood plasma of lipid oxygenated mediators and fatty acids using solid-phase extraction (SPE) and high-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS). The concurrent analysis of these lipid mediators is challenging because of their instability, differences in solubility, and the frequent occurrence of isobaric forms with similar fragmentation patterns. Results demonstrated that the reduction of SPE temperature to 4 °C is a critical parameter for preserving the hydroperoxy derivatives. Polymeric HLB cartridges increased 40-50 % ARA, EPA, and DHA sensitivity compared to C18 sorbent and also provided higher global performance for most hydroxides and other oxidation products. The proposed method for the two tested mass analyzers yields high sensitivity, good linearity, and reproducibility, with detection limits ranging 0.002-7 ng/mL and global recoveries as high as 85-112 %. However, the additional advantage of the linear ion trap (LIT) mass analyzer working in full scan product ion mode, compared to the triple quadrupole (QqQ) operating in multiple reaction monitoring (MRM), should be noted: the full scan product ion mode provides the full fragmentation spectra of compounds that allowed the discrimination of coeluting isomers and false positive identifications without additional chromatography development. The proposed lipidomic procedure demonstrates a confident, simple, and sensitive method to profile in plasma a wide range of lipid eicosanoid and docosanoid mediators, including innovatively the analysis of hydroperoxy congeners and nonoxidized PUFA precursors.

Development and Investigation of a Mesh-Electrode Linear Ion Trap (ME-LIT) Mass Analyzer

A mesh-electrode linear ion trap (ME-LIT) mass analyzer was developed and its performance was primarily characterized. In conventional linear ion trap mass analyzers, the trapped ions are mass-selected and then ejected in a radial direction by a slot on a trap electrode. The presence of slots can strongly affect the electric field distribution in the ion trapping region and distort the mass analysis performance. To compensate for detrimental electric field effects, the slot is usually designed and fabricated to be as small as possible, and also has very high mechanical accuracy and symmetry. A ME-LIT with several mesh electrodes was built to compensate for the effects caused by slots. Each mesh electrode was fabricated from a plate electrode with a relatively large slot and the slot was covered with a conductive mesh. Our preliminary experimental results show that the ME-LIT could considerably diminish the detrimental electric field effects caused by slots, and increase the mass resolving power and ion detection efficiency. Even with 4-mm-wide slots, a mass resolution in excess of 600 was obtained using the ME-LIT. Mass resolution could be remarkably improved using mesh electrodes in ion traps with asymmetric electrodes. The stability diagram of the ME-LIT was mapped, and highly efficient tandem mass spectrometry was demonstrated. The ME-LIT was qualified as a LIT mass analyzer. The ME-LIT can improve the mass resolution and decrease the requirements of mechanical accuracy and symmetry of slots, so it shows potential for a wide range of practical uses.

Modeling of an ion source lens system for sensitivity enhancement in a non-scanning linear ion trap

This article presents a novel simulation study for improving the sensitivity of linear ion trap mass spectrometers used for sensing low sample concentrations in field applications. Commercial simulation software using the boundary element method has been used for modeling ion source lens system for externally created ions, which are then injected into a 2D linear ion trap mass analyzer operating in a non-scanning mode. The geometric parameters of the ion source lens system were varied to investigate the effects on ion trap sensitivity by altering the number of ions injected into the analyzer and their focus. The performance results are given for cocaine (m/z 182 and 304) ions, showing significant improvement in sensitivity when the optimized lens system is used.

Laserspray and Matrix-Assisted Ionization Inlet Coupled to High-Field FT-ICR Mass Spectrometry for Peptide and Protein Analysis

We present the first coupling of laser spray ionization inlet (LSII) and matrix assisted ionization inlet (MAII) to high-field Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) for generation of electrospray-like ions to take advantage of increased sensitivity, mass range, and mass resolving power afforded by multiple charging. We apply the technique to top-down protein analysis and characterization of metalloproteins. We also present a novel method for generation of multiply-charged copper-peptide complexes with varying degrees of copper adduction by LSII. We show an application of the generated copper-peptide complexes for protein charge state and molecular weight determination, particularly useful for an instrument such as a linear ion trap mass analyzer.