Ion Trap Mass Spectrometer Research Articles

A Conjoined Rectilinear Collision Cell and Pulsed Extraction Ion Trap with Auxiliary DC Electrodes.

Ion traps are routinely directly coupled to mass analyzers, where they serve to suitably cool and shape an ion population prior to pulsed extraction into the analyzer proper. Such devices benefit from high duty cycle and transmission but suffer slow ion processing times caused by a compromise in the buffer gas pressure range that suitably dampens the ion kinetic energy without causing excessive scatter during extraction or within the analyzer. A rectilinear RF quadrupole ion trap has been characterized, conjoining a pressurized collision region with a pumped extraction region, and an unbroken RF interface for seamless ion transfer between them. Auxiliary electrodes mounted between the RF electrodes provide DC voltage gradients that serve to both guide ions through the device and position them at the extraction slot. The influence of the auxiliary DC upon the trapping RF field was measured, and suitable parameters were defined. A mode of operation was developed that allowed parallel processing of ions in both regions, enabling a repetition rate of 200 Hz when the device was coupled to a high-resolution accurate-mass analyzer.

Synchronous observation of information loss generating among ions in a long-range Paul trap chain

A one-dimensional chain of long-range vibrational trapped ions at low phonon temperatures is employed to simulate the arising and robustness of the information of nonlocal correlations among correlated and uncorrelated sites. We demonstrate that the direction of the acting global magnetic field in Paul’s trap controls the dynamics of correlations and entanglement between ions. Also, we analyze the robustness of the nonlocal correlations in the trap under the impact of ions vibrating and the interaction strength of ions by considering the distance between them. The criteria of concurrence entanglement, Bell inequality, and uncertainty-induced nonlocality are studied to detect the nonlocal correlations among ions that decide the fundamental resources of information in the chain. Furthermore, the analytical solution describing the decoherence equation under the ionic vibration in Paul’s trap is found to track encoded information in the chain.

The Beta-decay Paul Trap Mk IV: Design and commissioning

The Beta-decay Paul Trap is an open-geometry, linear trap used to measure the decays of 8Li and 8B to search for a tensor contribution to the weak interaction. In the latest 8Li measurement of Burkey et al. (2022), β scattering was the dominant experimental systematic uncertainty. The Beta-decay Paul Trap Mk IV reduces the prevalence of β scattering by a factor of 4 through a redesigned electrode geometry and the use of glassy carbon and graphite as electrode materials. The trap has been constructed and successfully commissioned with 8Li in a new data campaign that collected 2.6 million triple coincidence events, an increase in statistics by 30% with 4 times less β scattering compared to the previous 8Li data set.

Radial Electric Field Driven Collision-Induced Dissociation in a Miniature Continuous Atmospheric Pressure Interfaced Ion Trap Mass Spectrometer.

Miniature ion trap mass spectrometry with the unique ability of tandem-in-time analysis is extensively used in public security and environmental pollution detection. In this study, a novel radial electric field driven collision-induced dissociation (REFD-CID) is presented with high fragmentation efficiency for different species by adjusting the float DC, the initial kinetic energy of ions, and the pressure in a miniature continuous atmospheric pressure interfaced ion trap mass spectrometer (CAPI-ITMS). It is noteworthy that multiple fragment ions ([M+H-nC2H4]+, where n = 1, 2, 3) of triethyl phosphate were observed with a single injection of ions. The underlying mechanism of the REFD-CID revealed that the enhanced radial electric field by modulation of the float DC drove ions toward regions of intense RF field where broadband heating and dissociation of ions took place through theoretical simulations. Finally, the REFD-CID was utilized to improve the instrument performances. The existence of reagent ions led to a severe space charge effect as the ion injection duration of the CAPI-ITMS was extended to enhance the sensitivity of aniline. Through selective fragmentation of reagent ions, peak broadening and mass shift were eliminated, and meanwhile, a 28-fold improvement of aniline in a signal-to-noise ratio was achieved with the ion injection duration varying from 50 to 2500 ms. Moreover, isomeric illicit drugs (JWH-018 and acetylcodeine) were distinguished by generating multiple characteristic fragment ions, demonstrating potential applications in the identification of synthetic illicit drugs.

Systematic investigations on ion dynamics with noises in Paul trap

Ions confined in a Paul trap serve as crucial platforms in various research fields, including quantum computing and precision spectroscopy. However, the ion dynamics is inevitably influenced by different types of noise, which require accurate computations and general analytical analysis to facilitate diverse applications based on trapped ions with white or colored noise. In the present work, we investigate the motion of ions in a Paul trap via the Langevin equation using both analytical and numerical methods, systematically studying three different types of noise: the white noise, the colored noise via the Ornstein–Uhlenbeck process and the Wiener process. For the white noise of the case, we provide a recursion method to calculate ion motion for a wide range of parameters. Furthermore, we present an analytical solution to the more realistic stochastic process associated with the colored noise, verified by the Monte Carlo simulation. By comparing the results of the colored noise with those of the white noise, and additionally considering another limit of noise parameters corresponding to the Wiener process, we summarize the effects of different noise types on the ion dynamics.

Ultraviolet photodissociation and collision-induced dissociation for qualitative/quantitative analysis of low molecular weight compounds by liquid chromatography-mass spectrometry

Collision-induced dissociation (CID) is the most wildly used fragmentation technique for qualitative and quantitative determination of low molecular weight compounds (LMWC). Ultraviolet photodissociation (UVPD) has been mainly investigated for the analysis of peptides and lipids while only in a limited way for LMWC. A triple quadrupole linear ion trap instrument has been modified to allow ultraviolet photodissociation (UVPD) in the end of the q2 region enabling various workflows with and without data-dependent acquisition (DDA) combining CID and UVPD in the same LC–MS analysis. The performance of UVPD, with a 266-nm laser, is compared to CID for a mix of 90 molecules from different classes of LMWC including peptides, pesticides, pharmaceuticals, metabolites, and drugs of abuse. These two activation methods offer complementary fragments as well as common fragments with similar sensitivities for most analytes investigated. The versatility of UVPD and CID is also demonstrated for quantitative analysis in human plasma of bosentan and its desmethyl metabolite, used as model analytes. Different background signals are observed for both fragmentation methods as well as unique fragments which opens the possibility of developing a selective quantitative assay with improved sample throughput, in particular for analytes present in different matrices.Graphical

Proteomics identification of overexpressed serum proteins in dogs with Babesiacanis infection.

Canine babesiosis, caused by the protozoan parasite Babesia canis, is characterized by clinical manifestations, including hemolytic anemia, thrombocytopenia, multiple organ failure, and may result in death. This disease is detected using conventional blood smears, which are time-consuming and have low sensitivity. This study aimed to investigate a more rapid and sensitive method for detecting B. canis infection in dogs by examining the expressed serum protein profiles using proteomics. We collected six sera samples from three healthy and three B. canis-infected dogs diagnosed using blood smear and polymerase chain reaction. We analyzed the proteins using two-dimensional gel electrophoresis. The candidate spots from the gel were subjected to protein identification using a nano-liquid chromatography system coupled to an ion-trap mass spectrometer equipped with an electrospray ionization nano-sprayer. We found that 10 protein spots were overexpressed in the serum samples from infected dogs compared with healthy dogs, which corresponded to three proteins: serotransferrin, serotransferrin isoforms X1, and hemopexin. Furthermore, analysis of the protein-protein interaction network confirmed that they strongly interacted with each other. This study suggests that high levels of serotransferrin and hemopexin are related to B. canis infection, making these proteins potential candidates for the development of diagnostic molecules or vaccines.

Commissioning the digital mass-filter/ion-trap module for the MS SPIDOC prototype

The combination of a linear quadrupole ion-filter and linear Paul trap operated with a rectangular guiding field for the filtering and accumulation of ions within the Mass Spectrometry for Single Particle Imaging of Dipole Oriented protein Complexes (MS SPIDOC) prototype [T. Kierspel et al., Anal. Bioanal. Chem., published online] is characterized. Using cationic caesium-iodide clusters, the ion-separation performance, ion accumulation, cooling, and ejection via in-trap pin electrodes is evaluated. Furthermore, proof-of-principle measurements are performed with 64 kDa multiply-charged non-covalent protein complexes of human hemoglobin and 804 kDa non-covalent complex of GroEL, to demonstrate that the module meets the criteria to handle high-mass ions which are the main objective of the MS SPIDOC project. The setup's performance is found to be in line with previous results from ion-trajectory simulations [F. Simke et al., Int. J. Mass Spectrom. 473 (2022) 116779].

Differentiation of aminohydroxypropanesulfonic acid structural isomers using tandem mass spectrometry-based methods

d-Cysteinolic acid (D-CA) is an important metabolite within the biosulfur cycle. A structural isomer, (R)-3-amino-2-hydroxypropanesulfonate ((R)-AHPS), is less common in nature but potentially can be misidentified as D-CA due to their many shared physical properties. To support confident assignment of these two isomers by use of mass spectrometry alone, this study explores the fragmentation reactions of their [M+H]+ and [M−H]− ions using collision-induced dissociation (CID). Electrospray ionization mass spectrometry (ESI-MS) experiments were conducted on authentic standards using an ion trap mass spectrometer, while a triple-quadrupole (QqQ) mass spectrometer was used in the selective reaction monitoring (SRM) mode to record energy-resolved CID. Density-functional theory (DFT) calculations were carried out at the M06/6-31+G* level of theory to study gas-phase fragmentation mechanisms. The data generated revealed kinetically-controlled fragmentations involving participation of neighboring amino groups in the positive ion mode. Negative ion mode MS analysis could distinguish the structural isomers through different collision energy-resolved results for m/z 95 product ions, CH3SO3−. DFT calculations revealed an enthalpy (ΔH) (Gibbs energy (ΔG)) gap of 31.8 (31.4) kJ/mol between transition state barriers of a concerted mechanism for D-CA, and a more preferred stepwise mechanism for (R)-AHPS.

Gas-Phase Fragmentation as a Probe of G-Quadruplex Formation.

G-quadruplex (G4) DNA is found in oncogene promoters and human telomeres and is an attractive anticancer target. Stable G4 structures form in guanine-rich sequences in the presence of metal cations and can stabilize further with specific ligand adduction. To explore the preservation and stability of this secondary structure with mass spectrometry, gas-phase collision-induced dissociation kinetics of G4-like and non-G4-like ion structures were determined in a linear quadrupole ion trap. This study focused on a sequence from the promoter of the MYC oncogene, MycG4, and a mutant non-G4-forming sequence, MycNonG4. At relatively high ion activation energies, the backbone fragmentation patterns of the MycG4 and MycNonG4 are similar, while potassium ion-stabilized G4-folded [MycG4 + 2K-7H]5- and counterpart [MycG4-5H]5- ions are essentially indistinguishable, indicating that high-energy fragmentation is not sensitive to the G4 structure. At low energies, the backbone fragmentation patterns of MycG4 and MycNonG4 are significantly different. For MycG4, fragmentation over time differed significantly between the potassium-bound and free structures, reflecting the preservation of the G4 structure in the gas phase. Kinetic measurements revealed the [MycG4 + 2K-7H]5- ions to fragment two to three times more slowly than the [MycG4-5H]5-. Results for the control MycNonG4 indicated that the phenomena noted for [MycG4 + 2K-7H]5- ions are specific to G4-folding. Therefore, our data show that gentle activation conditions can lead to fragmentation behavior that is sensitive to G-quadruplex structure, revealing differences in kinetic stabilities of isomeric structures as well as the regions of the sequence that are directly involved in forming these structures.

Simulations and theory of power spectral density functions for time-dependent and anharmonic Langevin oscillators.

Simulations and theory are presented for the power spectral density functions (PSDs) of particles in time-dependent and anharmonic potentials, including the effects of a thermal environment leading to damping and fluctuating forces. We investigate three one-dimensional perturbations to the harmonic oscillator of which two are time-dependent changes in the natural frequency of the oscillator, while the other is a time-independent extension of the quadratic potential to include a quartic term. We investigate the effect of these perturbations on two PSDs of the motion that are used in experiments on trapped nano-oscillators. We also derive and numerically test the PSDs for the motion of a spherical nanoparticle in a Paul trap. We found that the simple harmonic Langevin oscillator's PSDs are good approximations for the x and y coordinates' PSDs for small values of the parameter q of the Mathieu equation, but the difference can be more than a factor of two as "q" increases. We also numerically showed that the presence of a permanent electric dipole on the nanosphere can significantly affect the PSDs in the x and y coordinates.

Trapping and Ground-State Cooling of a Single H_{2}^{+}.

We demonstrate co-trapping and sideband cooling of a H_{2}^{+}-^{9}Be^{+} ion pair in a cryogenic Paul trap. We study the chemical lifetime of H_{2}^{+} and its dependence on the apparatus temperature, achieving lifetimes of up to 11_{-3}^{+6} h at 10K. We demonstrate cooling of two of the modes of translational motion to an average phonon number of 0.07(1) and 0.05(1), corresponding to a temperature of 22(1) and 55(3) μK, respectively. Our results provide a basis for quantum logic spectroscopy experiments of H_{2}^{+}, as well as other light ions such as HD^{+}, H_{3}^{+}, and He^{+}.

Rapid analysis of pharmaceutical and personal care products by soft microwave-based plasma ionization-linear ion trap mass spectrometer (SMPI-LTQ) in natural water.

In this study, a soft microwave plasma torch (SMPT) combined with a mass spectrometer (MS) was used for the first time as an analytical method to detect and analyze various pharmaceutical and personal care products (PPCPs) in aquatic environments without the need for sample pretreatment. For this purpose, ambient SMPT was used to generate plasma for ionizing the analyte molecules. Accordingly, nine PPCPs were identified by the SMPT-MS, and their identification was verified by collision-induced dissociation (CID). The technique's performance was verified with known PPCP samples, and the limits of detection (LOD) and quantification (LOQ) obtained over a linear range of 50-1 μg/L were 1.56 to 2.81 and 2.07 to 3.62 μg/L, respectively, with the standard addition recovery rate falling between 87.14 and 115.16%. These results show that the method has excellent sensitivity and selectivity, suggesting that SMPT can rapidly and directly detect PPCPs in environmental water, making it a promising method for rapid water quality inspection.

Floating plastics as integrative samplers of organic contaminants of legacy and emerging concern from Western Mediterranean coastal areas

This study investigates the role of floating plastics as integrative samplers of organic contaminants. To this end, plastics items were collected in two Western Mediterranean coastal areas: the Mar Menor lagoon, and the last transect of Ebro river. Floating plastics were identified and characterized by attenuated total reflection Fourier-transform infrared spectrometry. Then, organic contaminants were extracted from plastic items by ultrasonic extraction with methanol, and the concentrations of 168 regulated and emerging contaminants were analysed. These compounds were analysed by stir bar sorptive extraction coupled to gas chromatography–mass spectrometry (GC–MS), except for bisphenol analogues, which were analysed with a ultraperformance liquid chromatography pump coupled to a triple quadrupole mass spectrometer (UHPLC-MS/MS), and pharmaceutical compounds, determined by UPLC coupled to hybrid triple quadrupole-linear ion trap mass spectrometer (UPLC-MS/MS). All the contaminants groups considered were detected in the samples, being particularly relevant the contribution of plastic additives. The most frequently detected contaminants were UV-filters, PAHs, pharmaceuticals and synthetic musks. Apart from plasticizers, the individual contaminants octocrylene, homosalate, galaxolide, salycilic acid and ketoprofen were frequently detected in plastics items. The results pointed out to urban and touristic activities as the main sources of pollution in the coastal areas investigated. The utility of floating plastics as integrative samplers for the detection of organic contaminants in aquatic ecosystems has been demonstrated.

Identification strategy of Fructus Gardeniae and its adulterant based on UHPLC/Q-orbitrap-MS and UHPLC-QTRAP-MS/MS combined with PLS regression model

Fructus Gardeniae (FG) is the desiccative and ripe fruits of Gardenia jasminoides Ellis in the Rubiaceae family, which is a commonly used in traditional Chinese medicine (TCM) for clearing away heat, detoxification, relieving restlessness, and eliminating blood stasis. At the same time, it has also been announced as the first batch of TCM with homology of medicine and food. Fructus Gardeniae Grandiflorae (FGG), the fruit of Gardenia jasminoides Ellis var. grandiflora Nakai (Rubiaceae), is a common counterfeit herbal medicine of FG, which still appears in the TCM market, and causes a certain degree of confusion. In order to effectively distinguish FG and its adulterant, the compounds in these two species were thoroughly characterized firstly by ultrahigh-performance liquid chromatography/quadrupole–orbitrap mass spectrometry (UHPLC/Q-Orbitrap MS). Furthermore, a pseudo-targeted metabonomics method with 60 targeted ion pairs was established based on UHPLC-triple quadrupole-linear ion trap mass spectrometry (UHPLC-QTRAP-MS) for discrimination. Multivariate statistical analysis showed that FG and FGG were clustered obviously, and 13 significantly differential markers were screened out by variable importance for projection (VIP) > 1 and p < 0.05 for the construction of the partial least squares (PLS) regression prediction model. The validation of the model proved that its prediction ability was quite satisfactory. Moreover, based on the absolute quantitative analysis of these 13 characteristics, the quality control standards of FG and FFG were established. In summary, an integral method of pseudo-targeted metabonomics combined with chemometrics analysis and a PLS regression model was proposed to provide an effective identification strategy for discrimination FG and FGG.

Tandem Mass-Selective Cryogenic Digital Ion Traps for Enhanced Cluster Formation.

We present the implementation of tandem mass-selective cryogenic ion traps, designed to enhance the range of ion processing capabilities that can be performed prior to spectroscopic interrogation. We show that both the formation of ion clusters and mass filtering steps can be combined in a single cryogenic linear quadrupole ion trap driven by RF square waves. Mass filtering and mass isolation can be achieved by manipulation of the RF frequency and duty cycle. Very importantly, this scheme circumvents the need for high-amplitude RF voltages that can be incompatible with typical cryogenic ion processing conditions. In addition, proper adjustment of the stability boundaries during the clustering process allows for the preferential formation of a specific cluster size rather than a broad distribution of sizes. Lastly, we show that a specific cluster size can be formed, mass-selected, and then transferred to another ion trap for a second completely separate ion processing step. The instrumentation and modular design developed here expand the scope of ionic species and clusters that can be accessed by processing electrosprayed ions.

Nonlinear Resonance in Dual-Frequency Paul Trap on Account of Hexapole Field Aberrations

Nonlinear Resonance in Dual-Frequency Paul Trap on Account of Hexapole Field Aberrations

Absolute Frequency Measurements of the D Lines in ^{9}Be^{+} Using a Single Trapped Ion.

Optical frequencies of the D line transitions in ^{9}Be^{+} were measured with a relative uncertainty of Δν/ν=5×10^{-11}. The results represent the highest accuracy achieved on a broad electric dipole-allowed (E1) transition in a trapped ion experiment to date, enabled in part by detailed consideration of photon recoil and quantum interference. Measurements were made on a single laser-cooled ion stored in a radio frequency Paul trap, using a spectroscopy laser stabilized to an optical frequency comb and referenced to UTC (NIST). The uncertainties in the D_{1} and D_{2} lines have been reduced by a factor of 10 and 30, respectively, compared to previous work. We have extracted the ^{2}P fine structure splitting, Δν_{fs}=197 064.54(7) MHz, and the ^{2}P_{1/2} hyperfine constant, A_{P_{1/2}}=-117.92(4) MHz.

Development of a High-Field "Brick" Mass Spectrometer with Extended Mass Range and Capable of Characterizing Native Proteins.

One of the main challenges of analyzing intact proteins on an ion trap mass spectrometer is the mass range limitation, especially for miniature mass spectrometers. In this study, a high-field frequency scanning ion trap miniature mass spectrometer, namely the high-field "Brick" mass spectrometer, was developed to analyze intact proteins. A high-voltage broadband radio frequency (rf) amplifier was designed with a maximum output of 900 Vp-p over a frequency range of 130-700 kHz. Compared to the 600 Vp-p rf amplifier equipped in the conventional "Brick" mass spectrometer, the mass range of the instrument could be extended from 2000 to over 8000 Th. Sensitivity and mass resolution for native protein analyses were also evaluated and compared. Various proteins as well as their mixtures were analyzed on the high-field "Brick" mass spectrometer. The noncovalent interaction between protein-ligand complexes, lysozyme with triN-acetylchitotriose, was also analyzed. In addition, a hybrid ion scan mode was explored to further expand the mass range of the instrument at both low- and high-mass ends. In the hybrid ion scan mode, both rf frequency and amplitude were tuned, and a mass range from 100 to 12,000 Th was realized. As a result, both small drugs and proteins could be analyzed in a single mass scan. As proof-of-concept demonstrations, a mixture of atenolol and bovine serum albuminand oligomers of transferrin were analyzed.

The elucidation of plasma lipidome profiles during severe influenza in a mouse model

Although influenza virus infection has been shown to affect lipid metabolism, details remain unknown. Therefore, we elucidated the kinetic lipid profiles of mice infected with different doses of influenza virus A/Puerto Rico/8/34 (H1N1) (PR8) by measuring multiple lipid molecular species using untargeted lipidomic analysis. C57BL/6 male mice were intranasally infected with PR8 virus at 50 or 500 plaque-forming units to cause sublethal or lethal influenza, respectively. Plasma and tissue samples were collected at 1, 3, and 6 days post-infection (dpi), and comprehensive lipidomic analysis was performed using high-performance liquid chromatography–linear trap quadrupole–Orbitrap mass spectrometry, as well as gene expression analyses. The most prominent feature of the lipid profile in lethally infected mice was the elevated plasma concentrations of phosphatidylethanolamines (PEs) containing polyunsaturated fatty acid (PUFA) at 3 dpi. Furthermore, the facilitation of PUFA-containing phospholipid production in the lungs, but not in the liver, was suggested by gene expression and lipidomic analysis of tissue samples. Given the increased plasma or serum levels of PUFA-containing PEs in patients with other viral infections, especially in severe cases, the elevation of these phospholipids in circulation could be a biomarker of infection and the severity of infectious diseases.