Laser Ionization Mass Spectrometry Research Articles

Machine Learning for Characterizing Biofuels Based on Femtosecond Laser Ionization Mass Spectrometry.

A sample mixture of fatty acid methyl esters (FAMEs) was measured by femtosecond laser ionization mass spectrometry (fsLIMS) using the fifth (206 nm) and fourth (257 nm) harmonic emissions of an ytterbium (Yb) laser (1030 nm). Molecular ions were observed as the major signals in this technique, providing valuable information concerning the molecular weight and the number of double bonds in the molecule. The mass spectral data were then used as explanatory variables in machine learning based on artificial intelligence (AI) to correlate with objective variables such as the cetane number, kinematic viscosity, specific gravity, a higher heating value, an iodine value, flash point, oxidative stability index, and a cloud point measured for reference biofuel samples containing various FAMEs. The properties of biofuels, i.e., the objective variables, were evaluated from the mass spectral data obtained for unknown samples. The errors in the evaluation were a few percent when the distribution of the FAMEs in the unknown biofuel sample was similar to those of the biofuels used for machine learning. As demonstrated herein, the present approach, involving a combination of fsLIMS and AI, has the potential for use in evaluating the properties of a biofuel and then in solving of environmental issues associated with global warming.

Tailoring Titanium Carbide Clusters for New Materials: from Met-Cars to Carbon-Doped Superatoms.

Tailoring materials with prescribed properties and regular structures is a critical and challenging research topic. Early transition metals were found to form supermagic M8C12 metallocarbohedrenes (Met-Cars); however, stable metal carbides are not limited to this common stoichiometry. Utilizing self-developed deep-ultraviolet laser ionization mass spectrometry, here, we report a strategy to generate new titanium carbides by reacting pure Tin clusters with acetylene. Interestingly, two products corresponding to Ti17C2 and Ti19C10 exhibit superior abundances in addition to the Ti8C12 Met-Cars. Using global-minimum search, the structures of Ti17C2 and Ti19C10 are determined to be an ellipsoidal D4d and a rod-shaped D5h geometry, respectively, both with carbon-capped Ti4C moieties and superatomic features. We illustrate the electronic structures and bonding nature in these carbon-doped superatoms concerning their enhanced stability and local aromaticity, shedding light on a new class of metal-carbide nanomaterials with atomic precision.

#2989 SELECTIVE RENAL DISPOSITION OF THE CALCINEURIN INHIBITORS VOCLSOPORIN, CYCLOSPORINE, AND TACROLIMUS

Abstract Background and Aims The calcineurin inhibitors (CNI) cyclosporine (CSA) and tacrolimus (TAC) were revolutionary immunosuppressants when first introduced for solid organ transplantation in the 1980s. Voclosporin (VCS), a novel CNI, recently became the first oral therapy approved in the United States, Great Britain, and Europe for the treatment of active lupus nephritis based on positive results from Phase 2 and 3 clinical trials. Unlike CSA and TAC, VCS has demonstrated a consistent pharmacokinetic and pharmacodynamic profile, eliminating the need for therapeutic drug monitoring. Further, VCS is associated with a more favorable metabolic profile and has not been associated with electrolyte disturbances. Emerging evidence indicates small molecule therapeutics may display differential disposition within organ tissues. This suggests that CNIs may be differentially distributed and retained in the kidney, potentially explaining the difference in their efficacy and safety profiles. To evaluate renal disposition of CSA, TAC, and VCS, we assessed in mice and humans the disposition of each CNI in the kidney relative to its systemic drug exposure. Method Single 30 mg/kg doses of CSA, TAC and VCS were administered intravenously to mice. Following intravenous administration, kidneys were collected at 15 minutes, 30 minutes, 1 hour and 2 hours, flash frozen in liquid nitrogen, and stored at −20 °C until sectioning. Sections of 10 μm kidney tissue were mounted on indium tin oxide coated glass slides. Matrix of 10 mg/mL α-Cyano-4-hydroxycinnamic acid in 85% acetonitrile/13% ethanol + 2% water + 0.1% trifluoroacetic acid was sprayed on the tissue using an HTX tissue sprayer, dried for 10 minutes in the vacuum, and subjected to Matrix-assisted Laser Desorption and Ionization Mass Spectrometry Imaging (MALDI-MSI). The systemic and renal clearance in humans of CSA and TAC were obtained from the literature; pharmacokinetic data on VCS was obtained from data on file. Renal secretion of each drug was compared to its expected passive filtration based on glomerular filtration rate (GFR), fraction unbound in plasma (fu), and respective systemic drug exposure. Results MALDI-MSI demonstrated significantly higher concentrations of drug and more diffuse tissue disposition of CSA in mouse kidney compared to VCS (Figure 1). CSA was retained in all kidney tissues up to 2 hours post-administration. Higher concentrations and more diffuse disposition of TAC was also noted compared to VCS at 15 and 30 minutes; TAC was distinctively retained in the cortex and medulla. VCS had moderate distribution in the cortex and was rapidly excreted with low levels of drug present in the kidney after 1 hour. According to published data, CSA has a measured renal clearance of 1.48 mL/min in healthy human subjects, representing approximately 10% of expected passive filtration of 12.5 mL/min (Table 1). TAC has a renal clearance of 0.014 mL/min representing <2% of expected passive filtration of 1.25 mL/min. VCS has a renal clearance of 7.82 mL/min representing approximately 200% of its expected passive filtration rate of 3.75 mL/min. Conclusion MALDI-MSI revealed differential retention and distribution of CSA, TAC and VCS in mice, consistent with their respective renal clearances in humans. Higher drug exposure and >90% renal reabsorption was observed for both CSA and TAC in this study, whereas the renal handling of VCS suggested a significant component of tubular secretion. The higher rate of secretion and lower overall exposure of kidney tissue to VCS may be associated with an improved safety profile when compared to the more diffuse distribution and greater renal retention of CSA and TAC.

Trace analysis of nitrated polycyclic aromatic hydrocarbons based on two-color femtosecond laser ionization mass spectrometry

Nitrated polycyclic aromatic hydrocarbons (nitro-PAHs) are suspected to be highly carcinogenic and mutagenic compounds that are present in the environment. Gas chromatography combined with mass spectrometry (GC-MS) is the most frequently used technique for trace analysis. The electron ionization techniques that are currently used in MS, however, typically do not result in the formation of a molecular ion, thus making the determination of these compounds more difficult. In this study, we report on the use of a compact highly-repetitive (low-pulse-energy) ultraviolet (UV) femtosecond laser as the ionization source in combination with a miniature time-of-flight mass analyzer and a time-correlated ion counting system. The UV laser pulses emitted at 343, 257, and 206 nm were produced by harmonic generations of a femtosecond Yb laser emitting at 1030 nm and were utilized for single-color multiphoton ionization. A combination of the 343-nm and 257-nm pulses was further employed to achieve two-color two-photon ionization. This technique was found to be more useful for sensitive detection and also resulted in the formation of a molecular ion. A pump-and-probe technique using these pulses was examined in a proof-of-concept study to measure the femtosecond lifetimes of the nitro-PAHs separated by GC, providing additional information for use in the characterization of the analyte. The developed technique was applied in the analysis of an authentic sample, an organic solvent extract from diesel exhaust particulates. The nitro-PAHs contained in a standard reference material (SRM1975) were determined on a two-dimensional GC-MS display, suggesting that this technique would be useful for the practical trace analysis of nitro-PAHs in environmental samples.

Resolving isobaric interference in the determination of Nd isotopes using laser ionisation mass spectrometry towards atom percent fission measurements

Use of LIMS for determination of Nd in the presence of Sm.

Metal Oxide Laser Ionization Mass Spectrometry Imaging of Fatty Acids and Their Double Bond Positional Isomers.

We present a novel combination of a metal oxide laser ionization mass spectrometry imaging (MOLI MSI) technique with off-line lipid derivatization by ozone for the detection of fatty acids (FA) and their carbon-carbon double bond (C═C) positional isomers in biological tissues. MOLI MSI experiments were realized with CeO2 and TiO2 nanopowders using a vacuum matrix-assisted laser desorption/ionization time-of-flight (MALDI TOF) mass spectrometer in the negative mode. The catalytic properties of these metal oxides allow FA cleavage from phospholipids under UV laser irradiation. At the same time, fragile ozonides produced at the sites of unsaturation decomposed, yielding four diagnostic ions specific for the C═C positions. Advantageously, two MOLI MSI runs from a single tissue sprayed with the metal oxide suspension were performed. The first run prior to ozone derivatization revealed the distribution of FAs, while the second run after the reaction with ozone offered additional information about FA C═C isomers. The developed procedure was demonstrated on MSI of a normal mouse brain and human colorectal cancer tissues uncovering the differential distribution of FAs down to the isomer level. Compared to the histological analysis, MOLI MSI showed the distinct distribution of specific FAs in different functional parts of the brain and in healthy and cancer tissues pointing toward its biological relevance. The developed technique can be directly adopted by laboratories with MALDI TOF analyzers and help in the understanding of the local FA metabolism in tissues.

Detection of Cosmic Fullerenes in the Almahata Sitta Meteorite: Are They an Interstellar Heritage?

Buckminsterfullerene, C60, is the largest molecule observed to date in interstellar and circumstellar environments. The mechanism of formation of this molecule is actively debated. Despite targeted searches in primitive carbonaceous chondrites, no unambiguous detection of C60 in a meteorite has been reported to date. Here we report the first firm detection of fullerenes, from C30 to at least C100, in the Almahata Sitta (AhS) polymict ureilite meteorite. This detection was achieved using highly sensitive laser desorption laser ionization mass spectrometry. Fullerenes have been unambiguously detected in seven clasts of AhS ureilites. Molecular family analysis shows that fullerenes are from a different reservoir compared to the polycyclic aromatic hydrocarbons detected in the same samples. The fullerene family correlates best with carbon clusters, some of which may have been formed by the destruction of solid carbon phases by the impacting laser. We show that the detected fullerenes are not formed in this way. We suggest that fullerenes are an intrinsic component of a specific carbon phase that has yet to be identified. The nondetection of fullerenes in the Murchison and Allende bulk samples, while using the same experimental conditions, suggests that this phase is absent or less abundant in these primitive chondrites. The former case would support the formation of fullerenes by shock-wave processing of carbonaceous phases in the ureilite parent body. However, there are no experimental data to support this scenario. This leaves open the possibility that fullerenes are an interstellar heritage and a messenger of interstellar processes.

Changes in the urine volatile metabolome throughout growth of transplanted hepatocarcinoma

Trained detection dogs distinguish between urine samples from healthy organisms and organisms with malignant tumors, suggesting that the volatile urine metabolome contains information about tumor progression. The aim of this study was to determine whether the stage of tumor growth affects the chemical differences in the urine of mice and to what extent the "olfactory image of disease" perceived by dogs coincides with the "image of disease" recorded by the mass spectrometer. We used a novel laser ionization mass spectrometry method and propose a mass spectrometric analysis without detailed interpretation of the spectrum of volatile metabolomes in urine. The mass spectrometer we use works without sample preparation and registers volatile organic compounds in air at room temperature without changing the pH of the sample, i.e. under conditions similar to those in which dogs solve the same problem. The experimental cancer models were male BDF-f1 hybrid mice transplanted with hepatocarcinoma tissue, and similar mice transplanted with healthy liver tissue were used as controls. Our data show that both dogs and our proposed laser mass spectrometry method are able to detect both the entire spectrum of volatile organic compounds associated with the disease and minor changes in this spectrum during its course.

Prato cheese with addition of Lactobacillus helveticus: Effect of culture preparation on peptide profile

This study evaluated the effect of the activation of Lactobacillus helveticus LH-B02 (40°C/18h), before its addition to Prato cheese manufacturing vat as an adjunct culture, on the cheese peptide profile. 62 peaks were detected in the cheese's peptide extracts by matrix-assisted laser ionization mass spectrometry (MALDI-MS) and the chemometric analysis of mass spectral data revealed that the addition of the adjunct culture to the cheese vat, either previously activated or not, modified the peptide profile of Prato cheese after 30 days of ripening. In general, the adjunct culture addition favored the release of β-casein derived peptides, particularly from β-casein C-terminal fraction, while reduced the relative intensity of αs1-casein derived peptides. The activation of the adjunct culture before its addition to the cheese vat resulted in higher differences in the peptides relative intensities than the direct addition of the adjunct culture without prior activation, when compared to the control Prato cheese.

Miniature time-of-flight mass analyzer for use in combination with a compact highly-repetitive femtosecond laser ionization source

In most cases, a molecular ion is observed in femtosecond laser ionization mass spectrometry, which provides information concerning the molecular weight of the analyte. However, the Ti:sapphire laser currently used as the ionization source is costly and involves special skills for operation and maintenance, which prevents its practical use in many applications. In this study, we report on the development of a miniature time-of-flight mass analyzer with a flight tube length of 65 mm for use in combination with a compact highly-repetitive (120–560 kHz) femtosecond Yb laser and a time-correlated single ion counting system. The fundamental beam (1030 nm) was converted into ultraviolet beams emitting at 343, 257, and 206 nm, which was utilized as an efficient two-photon ionization source. A mass resolution of 670 was achieved for the molecular ion of chlorobenzene, the minimum time for measuring a mass spectrum being 0.1 s. This mass spectrometer was used in the on-site real-time monitoring of products appeared by the combustion of plastic, some nerve agent analogs, and an explosive in the air. The interference arising from nitrogen and oxygen in the air was suppressed, since they require nonresonant four- and three-photon ionizations, respectively. The mass spectrometer was combined with a gas chromatograph and used for the comprehensive analysis of polycyclic aromatic hydrocarbons, suggesting its potential advantage for use in the practical trace analysis of organic compounds in the environmental and forensic sciences.

Fluorinated boron nitride nanosheets as an inorganic matrix for the MALDI mass spectrometry analysis of perfluoroalkyl acids

We report, for the first time, the application of fluorinated hexagonal boron nitride nanosheets (F-BNNs) as an effective inorganic matrix for matrix-assisted laser desorption and ionization mass spectrometry (MALDI-MS) analysis of perfluoroalkyl acids (PFAAs). Fluoride modification of F-BNNs increases both enrichment ability and ionization efficiency. The method was validated using environmental water, milk, human serum samples, and zebrafish imaging that has been previously exposed to PFAAs. The method provided in this work holds considerable promise in term of rapid analysis, sample requirement, and practicability.

Measuring Pb, Th, and U inter-element ratios in geological materials using extreme ultraviolet laser ablation and ionization mass spectrometry

An extreme ultraviolet laser, operating at a wavelength of 46.9 nm, is used to ablate and ionize glasses and minerals at the microscale followed by mass analysis using time-of-flight mass spectrometry to directly measure Pb-Th-U inter-element ratios.

In situ spatial glycomic imaging of mouse and human Alzheimer's disease brains.

N-linked protein glycosylation in the brain is an understudied facet of glucose utilization that impacts a myriad of cellular processes including resting membrane potential, axon firing, and synaptic vesicle trafficking. Currently, a spatial map of N-linked glycans within the normal and Alzheimer's disease (AD) human brain does not exist. A comprehensive analysis of the spatial N-linked glycome would improve our understanding of brain energy metabolism, linking metabolism to signaling events perturbed during AD progression, and could illuminate new therapeutic strategies. Herein we report an optimized in situ workflow for enzyme-assisted, matrix-assisted laser desorption and ionization (MALDI) mass spectrometry imaging (MSI) of brain N-linked glycans. Using this workflow, we spatially interrogated N-linked glycan heterogeneity in both mouse and human AD brains and their respective age-matched controls. We identified robust regional-specific N-linked glycan changes associated with AD in mice and humans. These data suggest that N-linked glycan dysregulation could be an underpinning of AD pathologies.

Comprehensive Analysis of Analogues of Amine-Related Psychoactive Substances Using Femtosecond Laser Ionization Mass Spectrometry.

Amine-related psychoactive molecules contain N-Cα and Cα-Cβ bonds, which easily dissociate to form various fragment ions in electron ionization mass spectrometry (EIMS). Therefore, observing a molecular ion and then determining the molecular weight of the analyte is difficult. In this study, we examined phenethylamine, 3,4-methylenedioxyphenethylamine, tryptamine, N-methylephedrine, and nicotine as well as analogues of amine-related psychoactive substances using EIMS and femtosecond laser ionization mass spectrometry (fs-LIMS) combined with gas chromatography for comprehensive analysis. A molecular ion was clearly observed in fs-LIMS for all of these compounds, which was in contrast to EIMS providing fragment ions dominantly (no molecular ion was observed for N-methylephedrine). This favorable result was obtained by adjusting the laser wavelength to the optimal value for two-photon ionization to minimize the excess energy remaining in the molecular ion. It therefore appears that fs-LIMS is superior to EIMS in terms of observing a molecular ion and would be potentially useful for identifying a variety of amine-related psychoactive substances, some of which are illegal and are of interest in the field of forensic science.

Esterification of perfluorinated carboxylic acids with bromomethyl aromatic compounds for gas chromatography combined with laser ionization mass spectrometry

Perfluorinated carboxylic acids (PFCAs) were derivatized with two types of aromatic compounds that contained a bromomethyl group, i.e., 2-(bromomethyl)naphthalene (BMN) and benzyl bromide (BB). The conditions for derivatization were optimized in terms of reaction temperature and time and the concentration of derivatizing reagent. Using these optimal conditions, the PFCAs-MN and PFCAs-B derivatives were measured by gas chromatography (GC) combined with mass spectrometry using an ultraviolet femtosecond laser (267 nm) as the ionization source. The efficiency of derivatization for PFCAs-B was higher than that for PFCAs-MN because of the smaller size of the chromophore (benzene). The ionization efficiency of PFCAs-MN, however, was better than PFCAs-B, since a larger sized chromophore (naphthalene) and then a larger molar absorptivity was preferable for resonance-enhanced two-photon ionization. Due to superior GC separation, BB was successfully used as the derivatizing agent for the trace analysis of PFCAs, with detection limits of 6.0, 8.4, and 9.5 ng/mL for perfluoroheptanoic, perfluorooctanoic, and perfluorononanoic acids, respectively. The other bromomethyl aromatic compounds were evaluated for use as a derivatization reagent in future studies.

Use of MALDI Mass Spectrometry Imaging to Identify Proteomic Signatures in Aortic Aneurysms after Endovascular Repair.

Endovascular repair (EVAR) has become the standard procedure in treating thoracic (TAA) or abdominal aortic aneurysms (AAA). Not entirely free of complications, a persisting perfusion of the aneurysm after EVAR, called Endoleak (EL), leads to reintervention and risk of secondary rupture. How the aortic wall responds to the implantation of a stentgraft and EL is mostly uncertain. We present a pilot study to identify peptide signatures and gain new insights in pathophysiological alterations of the aortic wall after EVAR using matrix-assisted laser desorption or ionization mass spectrometry imaging (MALDI-MSI). In course of or accompanying an open aortic repair, tissue sections from 15 patients (TAA = 5, AAA = 5, EVAR = 5) were collected. Regions of interest (tunica media and tunica adventitia) were defined and univariate (receiver operating characteristic analysis) statistical analysis for subgroup comparison was used. This proof-of-concept study demonstrates that MALDI-MSI is feasible to identify discriminatory peptide signatures separating TAA, AAA and EVAR. Decreased intensity distributions for actin, tropomyosin, and troponin after EVAR suggest impaired contractility in vascular smooth muscle cells. Furthermore, inability to provide energy caused by impaired respiratory chain function and continuous degradation of extracellular matrix components (collagen) might support aortic wall destabilization. In case of EL after EVAR, this mechanism may result in a weakened aortic wall with lacking ability to react on reinstating pulsatile blood flow.

Atmospheric Pressure Single Photon Laser Ionization (APSPLI) Mass Spectrometry Using a 157 nm Fluorine Excimer Laser for Sensitive and Selective Detection of Non- to Semipolar Hydrocarbons

Atmospheric pressure single photon ionization (APSPLI) mass spectrometry utilizing a fluorine excimer laser (157 nm, 7.9 eV) is presented for the first time. For evaluation and optimization, polycyclic aromatic hydrocarbon (PAH) standard mixtures were used. The presented technique allowed for the selective ionization of semi- to nonpolar compounds in a single photon ionization process using VUV photons. Molecular radical cations were found as a base peak, whereas protonated species were almost absent. Although the ionization chamber is flushed by pure nitrogen, remaining oxygen and water traces caused unwanted oxidized ionization artifacts. Installation of water and oxygen filter cartridges significantly reduced the abundance of artifacts. For evaluating complex mixture analysis, APSPLI was applied to characterize a light crude oil. In addition to aromatic hydrocarbons, APSPLI allowed for the sensitive ionization of sulfur-containing aromatic constituents (PASH). A comparison of APSPLI to atmospheric pressure laser ionization (266 nm, 4.7 eV) revealed the additional compositional space accessible by the single photon process. APLI, conducted with UV radiation, is mainly restricted to PAH analysis. APSPLI overcomes this limitation, and PAH and PASH, which often occur simultaneously in complex mixtures, can be detected. This novel ionization concept is envisioned to have a high analytical potential further explored in the future.

Resolving isobaric interference towards the determination of 137Cs and 90Sr using laser-ionization mass spectrometry

Resolving isobaric interference in situ using laser-ionization mass spectrometry (LIMS).

LASER IONIZATION MASS SPECTROMETRY AT 55: QUO VADIS?

Laser ionization mass spectrometry (LIMS) was one of the first practical methods developed for in situ analysis of the surfaces of solid samples. This review will encompass several aspects related to this analytical method. First, we will discuss the process of laser ionization, the influence of the laser type on its performance, and imaging capabilities of this method. In the second chapter, we will follow the historic development of LIMS instrumentation. After a brief overview of the first-generation instruments developed in 1960-1990 years, we will discuss in detail more recent designs, which appeared during the last 2-3 decades. In the last part of our review, we will cover the recent applications of LIMS for surface analysis. These applications include various types of analyses of solid inorganic, organic, and heterogeneous samples, often in combination with depth profiling and imaging capability.

Molecular content of nascent soot: Family characterization using two-step laser desorption laser ionization mass spectrometry

Molecules constituting nascent soot particles have been analyzed by two-step laser desorption laser ionization mass spectrometry. Three samples have been collected from a slightly sooting ethylene/air premixed flame with the aim to investigate soot composition in the transition from nucleated to just-grown soot particles. Sampling locations have been selected based on the evolution of the particle size distribution along the flame axis. The mass spectrometric results point to a strong evolution of the molecular composition. Just-nucleated soot is rich in polycyclic aromatic hydrocarbons (PAHs) dominated by medium sizes from 18 to 40 carbon atoms but containing sizes as large as 90 carbon atoms. Most abundant PAHs are in the form of peri-condensed structures. The presence of a large fraction of odd numbered carbon species shows that pentagonal cycles are a common feature of the detected population. Increasing the distance from the burner outlet, i.e., the particle residence time in flame, leads to an evolution of the chemical composition of this population with a major contribution of carbon clusters including also fullerenes up to about 160 carbon atoms. Our data support a scenario in which large PAHs containing pentagonal rings evolve very efficiently upon thermal processing by a series of dehydrogenation and isomerization processes to form fullerenes. This chemistry happens in the early steps of soot growth showing that carbonization is already active at this stage.