Types Of Mass Spectrometers Research Articles

Analysis of Rare Earth Elements in Rock and Mineral Samples by ICP-MS and LA-ICP-MS

AbstractThe group of the rare earth elements (REEs) serves as valuable indicator of numerous geological processes such as magma formation or fluid–rock interaction. The decay systems of the radioactive REE isotopesThe inductively coupled plasma (ICP) ion source and various types of mass spectrometers (MS) represent the basis to fulfil the analytical requirements of geoscientific studies. Today, ICP-quadrupole MS and ICP-sector field MS (SFMS) with a single detector or multiple ion collection (MC-ICP-MS) are standard instruments for REE analyses in the geosciences. Due to the need for in situ analysis, laser ablation (LA)-ICP-MS has become an important trace element microprobe technique, which is widely applied for determination of REE concentrations and isotope compositions in geoscientific laboratories.The quality of concentration analysis or isotope ratio determination of REEs by ICP-MS and LA-ICP-MS is affected by many parameters. Most significant are interferences caused by polyatomic oxide and hydroxide ion species formed in the plasma as well as fractionation effects leading to non-stoichiometric behaviour during element determination or to biased isotope ratio measurements. Laser-induced fractionation and isobaric interferences have to be considered as additional effects for LA-ICP-MS. As analyte elements and matrix are unseparated, mineral standards matching the matrix of samples are a prerequisite for accurate and precise REE concentration and isotope ratio determination. Application of fs lasers instead of the more common ns lasers in LA-ICP-MS systems turns out to be a significant step to reduce laser-induced fractionation and to overcome effects of sample matrices.

Foodomics and Food Safety: Where We Are.

The power of foodomics as a discipline that is now broadly used for quality assurance of food products and adulteration identification, as well as for determining the safety of food, is presented. Concerning sample preparation and application, maintenance of highly sophisticated instruments for both high-performance and high-throughput techniques, and analysis and data interpretation, special attention has to be paid to the development of skilled analysts. The obtained data shall be integrated under a strong bioinformatics environment. Modern mass spectrometry is an extremely powerful analytical tool since it can provide direct qualitative and quantitative information about a molecule of interest from only a minute amount of sample. Quality of this information is influenced by the sample preparation procedure, the type of mass spectrometer used and the analyst's skills. Technical advances are bringing new instruments of increased sensitivity, resolution and speed to the market. Other methods presented here give additional information and can be used as complementary tools to mass spectrometry or for validation of obtained results. Genomics and transcriptomics, as well as affinity-based methods, still have a broad use in food analysis. Serious drawbacks of some of them, especially the affinity-based methods, are the cross-reactivity between similar molecules and the influence of complex food matrices. However, these techniques can be used for pre-screening in order to reduce the large number of samples. Great progress has been made in the application of bioinformatics in foodomics. These developments enabled processing of large amounts of generated data for both identification and quantification, and for corresponding modeling.

GroupFilter: A software tool for efficient filtering of Morpheus search engine results

Morpheus is a search algorithm developed recently for high-resolution tandem mass spectra. According to the developers, its intrinsic property is discriminating short sequence length peptides. Therefore, elimination of direct comparisons between peptide spectrum matches (PSMs) for short and long peptides may potentially increase the search sensitivity for a given FDR level. In the proposed approach, all PSMs are grouped according to the number of matched fragment ions, followed by separate filtering of identifications in each group using target-decoy approach. The approach is applied to Morpheus output results and does not cause a significant increase in the overall data analysis time. The proposed approach was implemented as a Python command-line tool, called GroupFilter. Several data sets from different types of mass spectrometers were used for testing of the software, including the data from the original Morpheus search engine paper. Separate FDR filtering for grouped identifications increased the number of identified peptides by up to 18% compared with the default Morpheus post-processing procedure. The proposed approach can be considered as an addition to the Morpheus search engine.

Static mass spectrometers of new type, using Euler’s homogeneous electric and magnetic fields. I. General principle and single-stage systems

Static mass spectrometers are inconspicuous against the background of more modern and more sophisticated mass spectrometers, but their potentiality is far from being exhausted. One of the principle advantages of static mass spectrometers is that they are the only type of mass spectrometers with a “duty cycle” of 100%. However, to implement this advantage, a static mass analyzer should work in a spectrographic mode, covering a considerable range of masses in one measurement. However, systems with good spectrographic properties significantly differ from systems with good spectrometric properties from the optical point of view, and the development of such devices leads to completely new optical problems and, correspondingly, to new approaches to their solution. One of useful tools to solve these problems are specific electrostatic and magnetostatic fields, homogeneous in the Euler terms. In this paper, prospects for the use of Euler’s homogeneous fields in creating static mass analyzers of a new generation are discussed.

On the Statistical Significance of Compressed Ratios in Isobaric Labeling: A Cross-Platform Comparison.

Isobaric labeling is gaining popularity in proteomics due to its multiplexing capacity. However, copeptide fragmentation introduces a bias that undermines its accuracy. Several strategies have been shown to partially and, in some cases, completely solve this issue. However, it is still not clear how ratio compression affects the ability to identify a protein's change of abundance as statistically significant. Here, by using the "two proteomes" approach (E. coli lysates with fixed 2.5 ratios in the presence or absence of human lysates acting as the background interference) and manipulating isolation width values, we were able to model isobaric data with different levels of accuracy and precision in three types of mass spectrometers: LTQ Orbitrap Velos, Impact, and Q Exactive. We determined the influence of these variables on the statistical significance of the distorted ratios and compared them to the ratios measured without impurities. Our results confirm previous findings1-4 regarding the importance of optimizing acquisition parameters in each instrument in order to minimize interference without compromising precision and identification. We also show that, under these experimental conditions, the inclusion of a second replicate increases statistical sensitivity 2-3-fold and counterbalances to a large extent the issue of ratio compression.

Electric ion dispersion as a new type of mass spectrometer

At the 2014 Fields-MPrime Industrial Problem Solving Workshop, PerkinElmer presented a design problem for mass spectrometry. Traditionally, mass spectrometry is done via three methods: using magnetic fields to deflect charged particles whereby different masses bend differently; using a time-of-flight procedure where particles of different mass arrive at different times at a target; and using an electric quadrupole that filters out all masses except for one very narrow band. The challenge posed in the problem was to come up with a new design for mass spectrometry that did not involve magnetic fields and where mass fractions could be measured in an entire sample on a continuous basis. We found that by sending the sample particles down a channel of line charges oscillations would be induced with a spatial wavelength being mass dependent thereby allowing different masses to be separated spatially and potentially detected on a continuous basis, without the use of magnetic fields. In this paper, we present the analysis of our design and illustrate how this principle could be used for mass spectrometry.

Authentication of Closely Related Fish and Derived Fish Products Using Tandem Mass Spectrometry and Spectral Library Matching

Proteomics methodology has seen increased application in food authentication, including tandem mass spectrometry of targeted species-specific peptides in raw, processed, or mixed food products. We have previously described an alternative principle that uses untargeted data acquisition and spectral library matching, essentially spectral counting, to compare and identify samples without the need for genomic sequence information in food species populations. Here, we present an interlaboratory comparison demonstrating how a method based on this principle performs in a realistic context. We also increasingly challenge the method by using data from different types of mass spectrometers, by trying to distinguish closely related and commercially important flatfish, and by analyzing heavily contaminated samples. The method was found to be robust in different laboratories, and 94-97% of the analyzed samples were correctly identified, including all processed and contaminated samples.

A first dataset toward a standardized community-driven global mapping of the human immunopeptidome.

We present the first standardized HLA peptidomics dataset generated by the immunopeptidomics community. The dataset is composed of native HLA class I peptides as well as synthetic HLA class II peptides that were acquired in data-dependent acquisition mode using multiple types of mass spectrometers. All laboratories used the spiked-in landmark iRT peptides for retention time normalization and data analysis. The mass spectrometric data were deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD001872. The generated data were used to build HLA allele-specific peptide spectral and assay libraries, which were stored in the SWATHAtlas database. Data presented here are described in more detail in the original eLife article entitled ‘An open-source computational and data resource to analyze digital maps of immunopeptidomes’.

Bar Coding MS2 Spectra for Metabolite Identification

Metabolite identifications are most frequently achieved in untargeted metabolomics by matching precursor mass and full, high-resolution MS2 spectra to metabolite databases and standards. Here we considered an alternative approach for establishing metabolite identifications that does not rely on full, high-resolution MS2 spectra. First, we select mass-to-charge regions containing the most informative metabolite fragments and designate them as bins. We then translate each metabolite fragmentation pattern into a binary code by assigning 1’s to bins containing fragments and 0’s to bins without fragments. With 20 bins, this binary-code system is capable of distinguishing 96% of the compounds in the METLIN MS2 library. A major advantage of the approach is that it extends untargeted metabolomics to low-resolution triple quadrupole (QqQ) instruments, which are typically less expensive and more robust than other types of mass spectrometers. We demonstrate a method of acquiring MS2 data in which the third quadrupole of a QqQ instrument cycles over 20 wide isolation windows (coinciding with the location and width of our bins) for each precursor mass selected by the first quadrupole. Operating the QqQ instrument in this mode yields diagnostic bar codes for each precursor mass that can be matched to the bar codes of metabolite standards. Furthermore, our data suggest that using low-resolution bar codes enables QqQ instruments to make MS2-based identifications in untargeted metabolomics with a specificity and sensitivity that is competitive to high-resolution time-of-flight technologies.

Quantitative Profiling of Long-Chain Bases by Mass Tagging and Parallel Reaction Monitoring.

Long-chain bases (LCBs) are both intermediates in sphingolipid metabolism and potent signaling molecules that control cellular processes. To understand how regulation of sphingolipid metabolism and levels of individual LCB species impinge upon physiological and pathophysiological processes requires sensitive and specific assays for monitoring these molecules. Here we describe a shotgun lipidomics method for quantitative profiling of LCB molecules. The method employs a “mass-tag” strategy where LCBs are chemically derivatized with deuterated methyliodide (CD3I) to produce trimethylated derivatives having a positively charged quaternary amine group. This chemical derivatization minimizes unwanted in-source fragmentation of LCB analytes and prompts a characteristic trimethylaminium fragment ion that enables sensitive and quantitative profiling of LCB molecules by parallel reaction monitoring on a hybrid quadrupole time-of-flight mass spectrometer. Notably, the strategy provides, for the first time, a routine for monitoring endogenous 3-ketosphinganine molecules and distinguishing them from more abundant isomeric sphingosine molecules. To demonstrate the efficacy of the methodology we report an in-depth characterization of the LCB composition of yeast mutants with defective sphingolipid metabolism and the absolute levels of LCBs in mammalian cells. The strategy is generic, applicable to other types of mass spectrometers and can readily be applied as an additional routine in workflows for global lipidome quantification and for functional studies of sphingolipid metabolism.

Mass spectrometric signatures of the blood plasma metabolome for disease diagnostics.

In metabolomics, a large number of small molecules can be detected in a single run. However, metabolomic data do not include the absolute concentrations of each metabolite. Generally, mass spectrometry analyses provide metabolite concentrations that are derived from mass peak intensities, and the peak intensities are strictly dependent on the type of mass spectrometer used, as well as the technical characteristics, options and protocols applied. To convert mass peak intensities to actual concentrations, calibration curves have to be generated for each metabolite, and this represents a significant challenge depending on the number of metabolites that are detected and involved in metabolome-based diagnostics. To overcome this limitation, and to facilitate the development of diagnostic tests based on metabolomics, mass peak intensities may be expressed in quintiles. The present study demonstrates the advantage of this approach. The examples of diagnostic signatures, which were designed in accordance to this approach, are provided for lung and prostate cancer (leading causes of mortality due to cancer in developed countries) and impaired glucose tolerance (which precedes type 2 diabetes, the most common endocrinology disease worldwide).

Using Peptide-Level Proteomics Data for Detecting Differentially Expressed Proteins

The expression of proteins can be quantified in high-throughput means using different types of mass spectrometers. In recent years, there have emerged label-free methods for determining protein abundance. Although the expression is initially measured at the peptide level, a common approach is to combine the peptide-level measurements into protein-level values before differential expression analysis. However, this simple combination is prone to inconsistencies between peptides and may lose valuable information. To this end, we introduce here a method for detecting differentially expressed proteins by combining peptide-level expression-change statistics. Using controlled spike-in experiments, we show that the approach of averaging peptide-level expression changes yields more accurate lists of differentially expressed proteins than does the conventional protein-level approach. This is particularly true when there are only few replicate samples or the differences between the sample groups are small. The proposed technique is implemented in the Bioconductor package PECA, and it can be downloaded from http://www.bioconductor.org.

An open port sampling interface for liquid introduction atmospheric pressure ionization mass spectrometry.

A simple method to introduce unprocessed samples into a solvent for rapid characterization by liquid introduction atmospheric pressure ionization mass spectrometry has been lacking. The continuous flow, self-cleaning open port sampling interface introduced here fills this void. The open port sampling interface used a vertically aligned, co-axial tube arrangement enabling solvent delivery to the sampling end of the device through the tubing annulus and solvent aspiration down the center tube and into the ionization source of the mass spectrometer via the commercial APCI emitter probe. The solvent delivery rate to the interface was set to exceed the aspiration rate, creating a continuous sampling interface along with a constant, self-cleaning spillover of solvent from the top of the probe. Using the open port sampling interface with positive ion mode APCI and a hybrid quadrupole time-of-flight mass spectrometer, rapid, direct sampling and analysis possibilities are exemplified with plastics, ballpoint and felt tip ink pens, skin, and vegetable oils. These results demonstrated that the open port sampling interface could be used as a simple, versatile and self-cleaning system to rapidly introduce multiple types of unprocessed, sometimes highly concentrated and complex, samples into a solvent flow stream for subsequent ionization and analysis by mass spectrometry. The basic setup presented here could be incorporated with any self-aspirating liquid introduction ionization source (e.g., ESI, APCI, APPI, ICP, etc.) or any type of atmospheric pressure sampling-ready mass spectrometer system. The open port sampling interface provides a means to introduce and quickly analyze unprocessed solid or liquid samples with the liquid introduction atmospheric pressure ionization source without fear of sampling interface or ionization source contamination.

Overview of peptide and protein analysis by mass spectrometry.

Mass spectrometry is an indispensable tool for peptide and protein analysis owing to its speed, sensitivity, and versatility. It can be used to determine amino acid sequences of peptides, and to characterize a wide variety of post-translational modifications such as phosphorylation and glycosylation. Mass spectrometry can also be used to determine absolute and relative protein quantities, and can identify and quantify thousands of proteins from complex samples, which makes it an extremely powerful tool for systems biology studies. The main goals of this unit are to familiarize peptide and protein chemists and biologists with the types of mass spectrometers that are appropriate for the majority of their analytical needs, to describe the kinds of experiments that can be performed with these instruments on a routine basis, and to discuss the kinds of information that these experiments provide.

Characterization of in vitro metabolites of TM‐2, a potential antitumor drug, in rat, dog and human liver microsomes using liquid chromatography/tandem mass spectrometry

TM-2 (13-(N-Boc-3-i-butylisoserinoyl-4,10-β-diacetoxy-2-α-benzoyloxy-5-β,20-epoxy-1,13-α-dihydroxy-9-oxo-19-norcyclopropa[g]tax-11-ene) is a novel semi-synthetic taxane derivative. Our previous study demonstrated that it is a promising taxane derivative. The in vitro comparative metabolic profile of a drug between animals and humans is a key issue that should be investigated at early stages of drug development to better select drug candidates. In this study, the in vitro metabolic pathways of TM-2 in rat, dog and human liver microsomes were established and compared. TM-2 was incubated with liver microsomes in the presence of NADPH. Two different types of mass spectrometers - a hybrid linear trap quadrupole orbitrap (LC/LTQ-Orbitrap) mass spectrometer and a triple-quadrupole tandem mass spectrometer (LC/QqQ) were employed to acquire structural information of TM-2 metabolites. Accurate mass measurement using LC/LTQ-Orbitrap was used to determine the accurate mass data and elemental compositions of metabolites thereby confirming the proposed structures of the metabolites. For the chemical inhibition study, selective P450 inhibitors were added to incubations to initially characterize the cytochrome P450 (CYP) enzymes involved in the metabolism of TM-2. A total of 12 components (M1-M12) were detected and identified as the metabolites of TM-2 in vitro. M1-M5 were formed by hydroxylation of the taxane ring or the lateral chain. Hydroxylated products can be further oxidized to the dihydroxylated metabolites M6-M10. M11 was a trihydroxylated metabolite. M12 was tentatively identified as a carboxylic acid derivative. The metabolism of TM-2 is much the same in all three species with some differences. The chemical inhibition study initially demonstrated that the formation of M2, the major metabolite of TM-2, is mainly mediated by CYP3A4. Hydroxylation is the major biotransformation of the TM-2 pathway in vitro. CYP3A4 may play a dominant role in the formation of M2 in liver microsomes. The knowledge of the metabolic pathways of TM-2 is important to support further research of TM-2.

Conserved Peptide Fragmentation as a Benchmarking Tool for Mass Spectrometers and a Discriminating Feature for Targeted Proteomics

Quantifying the similarity of spectra is an important task in various areas of spectroscopy, for example, to identify a compound by comparing sample spectra to those of reference standards. In mass spectrometry based discovery proteomics, spectral comparisons are used to infer the amino acid sequence of peptides. In targeted proteomics by selected reaction monitoring (SRM) or SWATH MS, predetermined sets of fragment ion signals integrated over chromatographic time are used to identify target peptides in complex samples. In both cases, confidence in peptide identification is directly related to the quality of spectral matches. In this study, we used sets of simulated spectra of well-controlled dissimilarity to benchmark different spectral comparison measures and to develop a robust scoring scheme that quantifies the similarity of fragment ion spectra. We applied the normalized spectral contrast angle score to quantify the similarity of spectra to objectively assess fragment ion variability of tandem mass spectrometric datasets, to evaluate portability of peptide fragment ion spectra for targeted mass spectrometry across different types of mass spectrometers and to discriminate target assays from decoys in targeted proteomics. Altogether, this study validates the use of the normalized spectral contrast angle as a sensitive spectral similarity measure for targeted proteomics, and more generally provides a methodology to assess the performance of spectral comparisons and to support the rational selection of the most appropriate similarity measure. The algorithms used in this study are made publicly available as an open source toolset with a graphical user interface.

Present and Future Applications of High Resolution Mass Spectrometry in the Clinic.

High resolution mass spectrometers have directly enabled clinical applications of high clinical utility. These types of mass spectrometers are less known to the general public than their low resolution counterparts and are often ascribed to proteomics or biomarker discovery. This perception is rapidly changing as high resolution mass spectrometers see impact in the areas of clinical toxicology, forensic toxicology, microbiology, and molecular diagnostics as routine analyzers. Applications in these areas are made possible by the unique capacity of high resolution mass spectrometers, typically time-of flight or Orbitrap instruments, to characterize analytical species with sufficient mass resolution to better resolve molecular composition than lower resolution analyzers. This capacity confers a unique source of analytical specificity. In the future, this analytical specificity will likely be well applied to other clinical applications: mass spectrometry based tissue imaging, intraoperative determination of tumor boundaries, and evaluation of metabolic flux.

Studying the chemistry of cationized triacylglycerols using electrospray ionization mass spectrometry and density functional theory computations.

Analysis of triacylglycerols (TAGs), found as complex mixtures in living organisms, is typically accomplished using liquid chromatography, often coupled to mass spectrometry. TAGs, weak bases not protonated using electrospray ionization, are usually ionized by adduct formation with a cation, including those present in the solvent (e.g., Na(+)). There are relatively few reports on the binding of TAGs with cations or on the mechanisms by which cationized TAGs fragment. This work examines binding efficiencies, determined by mass spectrometry and computations, for the complexation of TAGs to a range of cations (Na(+), Li(+), K(+), Ag(+), NH4(+)). While most cations bind to oxygen, Ag(+) binding to unsaturation in the acid side chains is significant. The importance of dimer formation, [2TAG + M](+) was demonstrated using several different types of mass spectrometers. From breakdown curves, it became apparent that two or three acid side chains must be attached to glycerol for strong cationization. Possible mechanisms for fragmentation of lithiated TAGs were modeled by computations on tripropionylglycerol. Viable pathways were found for losses of neutral acids and lithium salts of acids from different positions on the glycerol moiety. Novel lactone structures were proposed for the loss of a neutral acid from one position of the glycerol moiety. These were studied further using triple-stage mass spectrometry (MS(3)). These lactones can account for all the major product ions in the MS(3) spectra in both this work and the literature, which should allow for new insights into the challenging analytical methods needed for naturally occurring TAGs.

Dynamic Observation of Hydrogen Gas Release during Crack Propagation in Al-Zn-Mg Alloy

We have developed a new testing device, which is capable of detecting hydrogen gas evolution from the microstructural changes at the same timing. The device is composed of the tensile testing machine equipped with a high-speed microscope and two types of quadrupole mass spectrometers installed in the ultrahigh vacuum chamber. Sampling rate of microscopic observation is 2000 fps. Hydrogen or deuterium was pre-charged to the 7075 aluminum alloy by means of the slow strain rate deformation, together with the exposure under the humid air atmosphere. The hydrogen amount was measured by using a thermal desorption analysis in advance. As a result, it was revealed that hydrogen gas was evolved when the surface crack was generated around the notch root of the test specimen. SEM observation also showed that the initial crack is related to the propagation of grain boundary fracture around the notch root. When compared to the microstructure and the hydrogen gas evolution near the notch root, the hydrogen amount evolved at the grain boundary was estimated to be about 3.0×10-7 mol/m2.

Measuring xenon in human plasma and blood by gas chromatography/mass spectrometry.

Due to the favorable pharmacokinetic properties and minimal side effects of xenon, its use in modern anesthesia has been well accepted, and recent studies further demonstrated the intra- and postoperative neuro-, cardio-, and reno-protective action of the noble gas. Since the production of the hypoxia-inducible factor 1α (HIF-1α) and its downstream effector erythropoietin as well as noradrenalin reuptake inhibition have been found to play key roles in this context, the question arose as to whether the use of xenon is a matter for doping controls and preventive doping research. The aim of the present study was hence to evaluate whether the (ab)use of xenon can be detected from doping control samples with the instrumentation commonly available in sports drug testing laboratories. Plasma was saturated with xenon according to reported protocols, and the target analyte was measured by means of gas chromatography/time-of-flight and triple quadrupole mass spectrometry with headspace injection. Recording the accurate mass of three major xenon isotopes at m/z 128.9048, 130.9045 and 131.9042 allowed for the unequivocal identification of the analyte and the detection assay was characterized concerning limit of detection (LOD), intraday precision, and specificity as well as analyte recovery under different storage conditions. Xenon was detected in fortified plasma samples with detection limits of approximately 0.5 nmol/mL to 50 nmol/mL, depending on the type of mass spectrometer used. The method characteristics of intraday precision (coefficient of variation <20%) and specificity demonstrated the fitness-for-purpose of the analytical approach to unambiguously detect xenon at non-physiological concentrations in human plasma and blood. Eventually, authentic plasma and blood samples collected pre-, intra-, and post-operative (4, 8, and 24 h) were positively analyzed after storage for up to 30 h, and provided proof-of-concept for the developed assay. If relevant to doping controls, xenon can be determined from plasma and blood samples, i.e. common specimens of routine sports drug testing in the context of Athlete Biological Passport (ABP) analyses. Optimization of sampling and analytical procedures will allow the detection limit to be further improved and potentially enable accurate quantification of the anesthetic agent.