Complete Mass Spectra Research Articles

Advancing elemental analysis by collision/reaction cell technology and micro-droplet calibration for bioimaging applications by LA-ICP-TOFMS

BackgroundBioimaging applications by laser ablation inductively coupled plasma time-of-flight mass spectrometry (LA-ICP-TOFMS) require comprehensive elemental analysis spanning the entire mass range. Within biological systems, endogenous elements are critical for maintaining metal homeostasis in cells, a fundamental aspect in disease progression when disrupted. Additionally, elements from the higher mass range may originate from various sources such as metal-tags for immuno-mass spectrometry, nanoparticles, or metal-based anticancer drugs. This study assesses the efficacy of collision/reacton cell (CCT) mode for simultaneously analysing elements across the complete mass spectrum. Furthermore, we demonstrate the accuracy of the LA-ICP-TOFMS methodology through the analysis of serum reference material. ResultsOur findings demonstrate that the CCT mode outperforms the standard/no gas mode for LA-ICP-TOFMS measurements, particularly in quantifying endogenous elements susceptible to interferences. Through the analysis of picolitre-volume micro-droplet standards and serum reference material (deposited as micro-droplets), we observed accurate quantification of elements such as iron and selenium, with isotope ratios closely resembling natural compositions. As key advantage, the utilization of the CCT mode eliminated the need for labor-intensive post-data processing, streamlining analytical procedures. Additionally, the CCT mode also provided enhanced sensitivity (factor of 1.5–2) for elements in the higher mass range compared to the standard mode, without compromising the sensitivity for endogenous elements. SignificanceWe successfully integrated Seronorm serum reference material-containing micro-droplets into LA-ICPMS bioimaging workflows for quality control, enabling validated measurements of key biological elements. The use of the CCT mode is highly recommended for bioimaging applications that address the analysis of elements across the entire mass range.

Comprehensive analysis of local and nonlocal amplitudes in the B0→ K*0μ+μ− decay

A comprehensive study of the local and nonlocal amplitudes contributing to the decay B0 → K*0(→ K+π−)μ+μ− is performed by analysing the phase-space distribution of the decay products. The analysis is based on pp collision data corresponding to an integrated luminosity of 8.4 fb−1 collected by the LHCb experiment. This measurement employs for the first time a model of both one-particle and two-particle nonlocal amplitudes, and utilises the complete dimuon mass spectrum without any veto regions around the narrow charmonium resonances. In this way it is possible to explicitly isolate the local and nonlocal contributions and capture the interference between them. The results show that interference with nonlocal contributions, although larger than predicted, only has a minor impact on the Wilson Coefficients determined from the fit to the data. For the local contributions, the Wilson Coefficient C9\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$ {\\mathcal{C}}_9 $$\\end{document}, responsible for vector dimuon currents, exhibits a 2.1σ deviation from the Standard Model expectation. The Wilson Coefficients C10\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$ {\\mathcal{C}}_{10} $$\\end{document}, C9′\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$ {\\mathcal{C}}_9^{\\prime } $$\\end{document} and C10′\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$ {\\mathcal{C}}_{10}^{\\prime } $$\\end{document} are all in better agreement than C9\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$ {\\mathcal{C}}_9 $$\\end{document} with the Standard Model and the global significance is at the level of 1.5σ. The model used also accounts for nonlocal contributions from B0→ K*0[τ+τ−→ μ+μ−] rescattering, resulting in the first direct measurement of the bsττ vector effective-coupling C9τ\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$ {\\mathcal{C}}_{9\ au } $$\\end{document}.

An integrated approach for studying the metabolic profiling of herbal medicine in mice using high-resolution mass spectrometry and metabolomics data processing tools

Analysis of exposure to traditional Chinese medicine (TCM) in vivo based on mass spectrometry is helpful for the screening of effective ingredients of TCM and the development of new drugs. The method of screening biomarkers through metabolomics technology is a nontargeted research method to explore the differential components between two sets of biological samples. By taking this advantage, this study aims to takes Forsythia suspensa, which is a TCM also known as Lian Qiao (LQ), as the research object and to study its in vivo exposure by using metabolomics technology. By comparing the significant differences between biological samples before and after administration, it could be focused on the components that were significantly upregulated, where a complete set of analysis strategies for nontargeted TCM in vivo exposure mass spectrometry was established. Furthermore, the threshold parameters for peak extraction, parameter selection during statistical data analysis, and sample concentration multiples in this method have also been optimized. More interestingly, by using the established analysis strategy, we found 393 LQ-related chemical components in mice after administration, including 102 prototypes and 291 LQ-related metabolites, and plotted their metabolic profiles in vivo. In short, this study has obtained a complete mass spectrum of LQ exposure in mice in vivo for the first time, which provides a reference for research on the active ingredients of LQ in vivo. More importantly, compared with other methods, the analysis strategy of nontargeted exposure of TCM in vivo-based mass spectrometry, constructed by using this research method, has good universality and does not require self-developed postprocessing software. It is worth mentioning that, for the identification and characterization of trace amounts of metabolites in vivo, this analysis strategy has no discrimination and has a detection capability similar to that of highly exposed components.

Mass spectrum in a six-dimensional SU(n) gauge theory on a magnetized torus

We examine six-dimensional SU(n) gauge theories compactified on a two-dimensional torus with a constant magnetic flux background to obtain a comprehensive low-energy mass spectrum. We introduce general background configurations including the magnetic flux and continuous Wilson line phases, consistent with classical equations of motion. Under the standard gauge fixing procedure, the complete mass spectrum in low-energy effective theory for the SU(n) case is newly presented without imposing restrictions on the gauge fixing parameter. Our analysis confirms the inevitable existence of tachyonic modes, which neither depend on the background configurations of Wilson line phases nor are affected by the gauge fixing parameter. Masses for some low-energy modes exhibit dependence on the gauge fixing parameter, and these modes are identified as would-be Goldstone bosons that are absorbed by massive four-dimensional vector fields. We discuss the phenomenological implications associated with stabilization or condensation of the tachyonic states. Various mass spectra and symmetry-breaking patterns are expected with flux backgrounds in the SU(n) case. They are helpful for constructing phenomenologically viable models beyond the standard model, such as gauge-Higgs unification and grand unified theories.

New methods for old problems: vacua of maximal D = 7 supergravities

Finding vacua of supergravity theories is an outstanding problem which has been tackled in several ways, and with this work we add a new method to the puzzle. We analyse the scalar sector of maximal gauged supergravity theories in seven space-time dimensions. We look for vacua of the theory by varying the embedding tensor, instead of directly minimising the scalar potential. The set of quadratic constraints arising from this procedure has been solved by means of Evolution Strategies optimisation techniques, also adopted in Artificial Intelligence studies. We develop some methods to reconstruct and obtain analytical results starting from numerical outcomes, thus obtaining the complete mass spectra. In addition to some of the known vacua, we also obtain two new Minkowski vacua.

Towards top-down holographic composite Higgs: minimal coset from maximal supergravity

Within the context of top-down holography, we study a one-parameter family of regular background solutions of maximal gauged supergravity in seven dimensions, dimensionally reduced on a 2-torus. The dual, four-dimensional confining field theory realises the global (spontaneous as well as explicit) symmetry breaking pattern SO(5) → SO(4). We compute the complete mass spectrum for the fluctuations of the 128 bosonic degrees of freedom of the five-dimensional gravity theory, which correspond to scalar, pseudoscalar, vector, axial-vector, and tensor bound states of the dual field theory, and includes particles with exotic SO(4) quantum numbers. We confirm the existence of tachyonic instabilities near the boundaries of the parameter space.We discuss the interplay between explicit and spontaneous symmetry breaking. The SO(5)/SO(4) coset might provide a first step towards the realisation of a calculable framework and ultraviolet completion of minimal composite Higgs models, if the four pseudo-Nambu-Goldstone bosons are identified with the real components of the Higgs doublet in the standard model (SM), and a subgroup of SO(4) with the SU(2) × U(1) SM gauge group. We exhibit an example with an additional localised boundary term that mimics the effect of a weakly-coupled external sector.

KDClassifier: A urinary proteomic spectra analysis tool based on machine learning for the classification of kidney diseases

Background: We aimed to establish a novel diagnostic model for kidney diseases by combining artificial intelligence with complete mass spectrum information from urinary proteomics. Methods: We enrolled 134 patients (IgA nephropathy, membranous nephropathy, and diabetic kidney disease) and 68 healthy participants as controls, with a total of 610,102 mass spectra from their urinary proteomic profiles. The training data set (80%) was used to create a diagnostic model using XGBoost, random forest (RF), a support vector machine (SVM), and artificial neural networks (ANNs). The diagnostic accuracy was evaluated using a confusion matrix with a test dataset (20%). We also constructed receiver operating-characteristic, Lorenz, and gain curves to evaluate the diagnostic model. Results: Compared with the RF, SVM, and ANNs, the modified XGBoost model, called Kidney Disease Classifier (KDClassifier), showed the best performance. The accuracy of the XGBoost diagnostic model was 96.03%. The area under the curve of the extreme gradient boosting (XGBoost) model was 0.952 (95% confidence interval, 0.9307–0.9733). The Kolmogorov-Smirnov (KS) value of the Lorenz curve was 0.8514. The Lorenz and gain curves showed the strong robustness of the developed model. Conclusions: The KDClassifier achieved high accuracy and robustness and thus provides a potential tool for the classification of kidney diseases

Characterization of polymeric surfaces and interfaces using time‐of‐flight secondary ion mass spectrometry

AbstractTime‐of‐flight secondary ion mass spectrometry (ToF‐SIMS) is used for chemical analysis of surfaces. ToF‐SIMS is a powerful tool for polymer science because it detects a broad mass range with good mass resolution, thereby distinguishing between polymers that have similar elemental compositions and/or the same types of functional groups. Chemical labeling techniques that enhance contrast, such as deuterating or staining one constituent, are generally unnecessary. ToF‐SIMS can generate both two‐dimensional images and three‐dimensional depth profiles, where each pixel in an image is associated with a complete mass spectrum. This Review begins by introducing the principles of ToF‐SIMS measurements, including instrumentation, modes of operation, strategies for data analysis, and strengths/limitations when characterizing polymer surfaces. The sections that follow describe applications in polymer science that benefit from characterization by ToF‐SIMS, including thin films and coatings, polymer blends, composites, and electronic materials. The examples selected for discussion showcase the three standard modes of operation (spectral analysis, imaging, and depth profiling) and highlight practical considerations that relate to experimental design and data processing. We conclude with brief comments about broader opportunities for ToF‐SIMS in polymer science.

Towards a complete mass spectrum of type-IIB flux vacua at large complex structure

The large number of moduli fields arising in a generic string theory compactification makes a complete computation of the low energy effective theory infeasible. A common strategy to solve this problem is to consider Calabi-Yau manifolds with discrete symmetries, which effectively reduce the number of moduli and make the computation of the truncated Effective Field Theory possible. In this approach, however, the couplings (e.g., the masses) of the truncated fields are left undetermined. In the present paper we discuss the tree-level mass spectrum of type-IIB flux compactifications at Large Complex Structure, focusing on models with a reduced one-dimensional complex structure sector. We compute the tree-level spectrum for the dilaton and complex structure moduli, including the truncated fields, which can be expressed entirely in terms of the known couplings of the reduced theory. We show that the masses of this set of fields are naturally heavy at vacua consistent with the KKLT construction, and we discuss other phenomenologically interesting scenarios where the spectrum involves fields much lighter than the gravitino. We also derive the probability distribution for the masses on the ensemble of flux vacua, and show that it exhibits universal features independent of the details of the compactification. We check our results on a large sample of flux vacua constructed in an orientifold of the Calabi-Yau {mathbbm{W}mathrm{mathbb{P}}}_{left[1,1,1,1,4right]}^4 . Finally, we also discuss the conditions under which the spectrum derived here could arise in more general compactifications.

A device for controlling the energy of ionizing electrons in the low-energy range designed to form a complete mass spectrum of negative ions using a quadrupole mass spectrometer

Operation with positive ions formed from the impact of high energy electrons (usually 70 eV, which exceeds the ionization energy of the molecules) is a standard mode for mass spectrometric detectors of most gas chromatography-mass spectrometric complexes (GC/MS) in the basic configuration. At the same time, we have shown that the option of setting the energy of ionizing electrons (maintained in the design of some serial devices) within the pre-ionization region also allows one to obtain mass spectra of negative ions (NI) which, in turn, significantly expands the analytical potential of standard equipment. The formation of NI occurs in the low-energy range of 0 – 15 eV due to resonant capture of electrons by molecules (REC). In contrast to positive ions, the intensity of NI formation sharply (resonantly) depends on the electron energy and this dependence is characteristic of each chemical compound. Both the relative intensity of the mass-peaks and, in general, the ionic composition of the formed mass spectrum of NI significantly depend on the electron energy. The problem of choosing the optimal energy of ionizing electrons providing the same efficiency of mass-spectrometric determination of all components of complex mixtures of dissimilar compounds is also associated with the features of negative ion formation during chromatography-mass spectrometric analysis. To address the problem, we propose a technique providing generation of complete (in NI composition and intensities) mass spectra of NI through repeated variation of the energy of ionizing electrons in a given range of 0 – 10 eV. Technical implementation of the technique [1] was carried out at the Design Bureau «Chromatec «(Yoshkar Ola, Russia) in the form of a special electronic device, which was tested in pilot operation as part of the gas chromatograph complex with a quadrupole mass spectrometer «Chromatec». We describe the principle of operation of the device and present the results of tests.

Hidden-charm and hidden-bottom molecular pentaquarks in chiral effective field theory

The newly observed Pc(4312), Pc(4440) and Pc(4457) at the LHCb experiment are very close to the {varSigma}_coverline{D} and {varSigma}_c{overline{D}}^{ast } thresholds. In this work, we perform a systematic study and give a complete picture on the interactions between the {varSigma}_c^{left(ast right)} and {overline{D}}^{left(ast right)} systems in the framework of heavy hadron chiral effective field theory, where the short-range contact interaction, long-range one-pion-exchange contribution, and intermediate-range two-pion-exchange loop diagrams are all considered. We first investigate the three Pc states without and with considering the Λc contribution in the loop diagrams. It is difficult to simultaneously reproduce the three Pcs unless the Λc is included. The coupling between the {varSigma}_c^{left(ast right)}{overline{D}}^{left(ast right)} and {Lambda}_c{overline{D}}^{left(ast right)} channels is crucial for the formation of these Pcs. Our calculation supports the Pc(4312), Pc(4440) and Pc(4457) to be the S-wave hidden-charm {left[{varSigma}_coverline{D}right]}_{J=1/2}^{I=1/2},{left[{varSigma}_c{overline{D}}^{ast}right]}_{J=1/2}^{I=1/2} and {left[{varSigma}_c{overline{D}}^{ast}right]}_{J=3/2}^{I=1/2} molecular pentaquarks, respectively. Our calculation disfavors the spin assignment {J}^P=frac{1^{-}}{2} for Pc(4457) and {J}^P=frac{3^{-}}{2} for Pc(4440), because the excessively enhanced spin-spin interaction is unreasonable in the present case. We obtain the complete mass spectra of the {left[{varSigma}_c^{left(ast right)}{overline{D}}^{left(ast right)}right]}_J systems with the fixed low energy constants. Our result indicates the existence of the {left[{varSigma}_c^{ast }{overline{D}}^{ast}right]}_Jleft(J=frac{1}{2},frac{3}{2},frac{5}{2}right) hadronic molecules. The previously reported Pc(4380) might be a deeper bound one. Additionally, we also study the hidden-bottom {varSigma}_b^{left(ast right)}{B}^{left(ast right)} systems, and predict seven bound molecular states, which could serve as a guidance for future experiments. Furthermore, we also examine the heavy quark symmetry breaking effect in the hidden-charm and hidden-bottom systems by taking into account the mass splittings in the propagators of the intermediate states. As expected, the heavy quark symmetry in the bottom cases is better than that in the charmed sectors. We notice that the heavy quark symmetry in the {varSigma}_coverline{D} and {varSigma}_c^{ast}overline{D} systems is much worse for some fortuitous reasons. The heavy quark symmetry breaking effect is nonnegligible in predicting the effective potentials between the charmed hadrons.

Quantification of Cytokinins Using High-Resolution Accurate-Mass Orbitrap Mass Spectrometry and Parallel Reaction Monitoring (PRM).

Cytokinins (CKs) are adenine derivatives that act as phytohormones. These signaling molecules control plant cell division and differentiation, organ growth, and senescence, and they orchestrate plant interactions with biotic and abiotic environments. While CKs are predominately recognized as plant-based substances, CKs have been found across different domains of life, including microorganisms, insects, mammals, and humans. In plants, CKs act at trace, often low femtomolar concentrations; therefore, sensitive and precise analytical techniques are required to accurately detect and quantify them from complex biological matrices. Here, we report the first comprehensive CK quantification method using a QExactive Orbitrap mass spectrometer in high-resolution with a parallel reaction monitoring (PRM)-based approach. The current method progresses upon multiple reaction monitoring (MRM) methods, previously used for CK profiling on triple quadrupole mass spectrometers. This method offers improved mass accuracy and the complete product ion mass spectra (MS/MS) for compound determination with increased specificity, and sensitivity comparable with triple quadrupole instruments. The presented PRM approach was successfully applied to quantify 32 CKs in several biological samples.

The DBP exposome: Development of a new method to simultaneously quantify priority disinfection by-products and comprehensively identify unknowns

Disinfected drinking water contains hundreds of disinfection by-products (DBPs) that are formed by the reaction of disinfectants with natural and anthropogenic organic matter, bromide, and iodide. Understanding what these DBPs are is important because millions of people worldwide consume drinking water every day, and human epidemiologic studies have reported cancer, miscarriage, and birth defects from consuming such waters. While more than 600 DBPs are reported in the literature, very few studies quantify complete classes of chlorinated, brominated, and iodinated DBPs. Also, very few studies conduct comprehensive non-target analyses of unknown DBPs to characterize the complete DBP exposure (the exposome). We developed a new gas chromatography (GC)-mass spectrometry (MS) method that simultaneously quantifies 39 priority unregulated DBPs from six different chemical classes (haloacetaldehydes, haloketones, haloacetamides, haloacetonitriles, halonitromethanes, and iodinated-trihalomethanes) and analyzes unknown DBPs with mass accuracy <600 ppm under full-scan conditions. Using a new type of time-of-flight (TOF) mass spectrometer, which combines selected ion monitoring (SIM)-level sensitivity with mass accuracy of ±0.05 Da, method detection limits of 3–61 ng/L were achieved. These levels were found to be quite comparable to those of a widely used single quadrupole mass spectrometer (2–90 ng/L) operated in SIM mode. However, analysis using this TOF mass spectrometer offers two additional advantages over traditional quadrupole-MS: (1) full-scan data, which provides additional confidence for target analytes, as well as complete mass spectra for unknown analysis, and (2) two decimal place mass accuracy, which allows additional confidence for target analytes and importantly, molecular formula indication for unknowns. High resolution accurate mass TOF was also used to validate identification of selected compounds. This new method was demonstrated on finished drinking waters from three different drinking water plants, where target quantification and non-target unknown analyses were performed simultaneously during the same run. This enabled the quantification of 39 DBPs, along with the non-target identification of many other drinking water contaminants, including two additional non-target DBPs: N,N-dimethylacetamide and N-nitrosodibutylamine.

Identification of volatiles from heated tobacco biomass using direct thermogravimetric analysis—Mass spectrometry and target factor analysis

Target Factor Analysis (TFA) was used to identify full spectral profiles in the presence of complex overlapping signals in mass spectrometry data. This allowed interpretation of direct thermogravimetric analysis-mass spectrometry (TGA-MS) data from two varieties of tobacco biomass, heated below 350 °C. Previous TGA-MS approaches reported in biomass research use Selected Ion Monitoring (SIM) to monitor specific ions in the evolved gases. This cannot distinguish between isobaric mass fragments, and is challenged by the complex mixture of volatiles evolved from tobacco biomass. The TFA approach instead uses the complete reference mass spectra of the target compounds. Eighteen mass spectral references were used as target compounds to test their qualitative presence, based on correlations between the target spectra and the predicted spectra from the TFA process. Both simulated and experimental data sets were used to evaluate this approach.Empirical statistical analysis recommended 7 or 8 principal components for our data, but investigating predictive capabilities beyond these levels revealed correlation trends and enhanced analytical insights. Based on this multivariate analytical strategy, which we call a “deep search”, it was found that there was a distinction between identifiable and nonidentifiable spectral groupings for the 18 target references chosen. The nonidentifiable targets persistently scored below 0.55 correlation coeffecient (R), even when the search was based on two to three times the empirically recommended number of factors.The results show that components present in a complex data matrix, generated from TGA-MS experiments on complex biomass materials could be identified by full spectral matching using TFA instead of SIM.

Analysis of Inorganic Nanoparticles by Single-particle Inductively Coupled Plasma Time-of-Flight Mass Spectrometry.

Due to the rapid development of nanotechnologies, engineered nanomaterials (ENMs) and nanoparticles (ENPs) are becoming a part of everyday life: nanotechnologies are quickly migrating from laboratory benches to store shelves and industrial processes. As the use of ENPs continues to expand, their release into the environment is unavoidable; however, understanding the mechanisms and degree of ENP release is only possible through direct detection of these nanospecies in relevant matrices and at realistic concentrations. Key analytical requirements for quantitative detection of ENPs include high sensitivity to detect small particles at low total mass concentrations and the need to separate signals of ENPs from a background of dissolved elemental species and natural nanoparticles (NNPs). To this end, an emerging method called single-particle inductively coupled plasma mass spectrometry (sp-ICPMS) has demonstrated great potential for the characterization of inorganic nanoparticles (NPs) at environmentally relevant concentrations. Here, we comment on the capabilities of modern sp-ICPMS analysis with particular focus on the measurement possibilities offered by ICP-time-of-flight mass spectrometry (ICP-TOFMS). ICP-TOFMS delivers complete elemental mass spectra for individual NPs, which allows for high-throughput, untargeted quantitative analysis of dispersed NPs in natural matrices. Moreover, the multi-element detection capabilities of ICP-TOFMS enable new NP-analysis strategies, including online calibration via microdroplets for accurate NP mass quantification and matrix compensation.

(Invited) Modification and Analysis of Carbon Based Structures By Metal Nanoparticulate Ions

Our collaborative work to create and soft land ionized gas phase single crystalline metal nanoparticulate ions onto substrates was motivated by Robert Hauge’s wish to produce templates for carbon nanotube carpet growth. Ionwerks created a machine to do this but, as is often the case, funding was found first for alternative applications. One such has been low energy (500 eV) injection of 8 nm silver nanoparticulate ions (AgNP-) into the near surface of bio-polymers. A uniform layer (70 e15 Ag atoms/cm2) of these implanted particles serve to assist the laser desorption of intact biomolecules from a brain tissue sample into the gas phase. Some of these desorbed molecules are ionized and can be transported into a mass spectrometer and uniquely identified by their exact mass to charge (m/z). By scanning a 50 micron focused laser across the surface of an AgNP implanted rat brain tissue sections, a complete mass spectrum can be acquired at each of several hundred thousand laser locations. Images of specific biomolecules can be derived from these spectra. Putative molecular biomarkers can then be identified by inter-comparing the numerous molecular images from each animal grouping within an animal study. Images from the same brain levels between injured (or diseased) and uninjured rats define histological micro domains in which elevated or decreased molecular ion intensities correlate with other measures of injury/disease state severity. Imaging of these biomarker ions is becoming useful in preclinical screening of drug candidates and should ultimately enter clinical settings. The AgNP enhanced mass spectral imaging has been also applied to the surface analysis of synthetic polymers, fullerenes, and nanotubes. A third application uses 30 keV, 15 nm AgNP ion impacts to form otherwise unattainable controlled nano-sized holes in graphene—especially “rebar” graphene. Alternatively, low energy soft landing at lower energy can form nanostructures upon the graphene which have implications for device formation. However, before departure, Bob made it clear that we needed to get back to carpet growth and other ideas which he outlined in extensive and explicit discussions—mostly at outdoor cafes and coffee shops. His dictates and imprimatur remain.

A complete workflow for high-resolution spectral-stitching nanoelectrospray direct-infusion mass-spectrometry-based metabolomics and lipidomics.

Metabolomic and lipidomic studies measure and discover metabolic and lipid profiles in biological samples, enabling a better understanding of the metabolism of specific biological phenotypes. Accurate biological interpretations require high analytical reproducibility and sensitivity, and standardized and transparent data processing. Here we describe a complete workflow for nanoelectrospray ionization (nESI) direct-infusion mass spectrometry (DIMS) metabolomics and lipidomics. After metabolite and lipid extraction from tissues and biofluids, samples are directly infused into a high-resolution mass spectrometer (e.g., Orbitrap) using a chip-based nESI sample delivery system. nESI functions to minimize ionization suppression or enhancement effects as compared with standard electrospray ionization (ESI). Our analytical technique-named spectral stitching-measures data as several overlapping mass-to-charge (m/z) windows that are subsequently 'stitched' together, creating a complete mass spectrum. This considerably increases the dynamic range and detection sensitivity-about a fivefold increase in peak detection-as compared with the collection of DIMS data as a single wide mass-to-charge (m/z ratio) window. Data processing, statistical analysis and metabolite annotation are executed as a workflow within the user-friendly, transparent and freely available Galaxy platform (galaxyproject.org). Generated data have high mass accuracy that enables molecular formulae peak annotations. The workflow is compatible with any sample-extraction method; in this protocol, the examples are extracted using a biphasic method, with methanol, chloroform and water as the solvents. The complete workflow is reproducible, rapid and automated, which enables cost-effective analysis of >10,000 samples per year, making it ideal for high-throughput metabolomics and lipidomics screening-e.g., for clinical phenotyping, drug screening and toxicity testing.

Characterization and identification of minerals in rocks by ToF-SIMS and principal component analysis

Time-of-flight secondary ion mass spectrometry (ToF-SIMS) was used to characterize and identify minerals in rock samples. ToF-SIMS provides a vast amount of information due to the recording of complete mass spectra with elemental and molecular ion signals. For an efficient handling of this amount of data multivariate analysis (MVA) techniques are useful tools. Initially principal component analysis (PCA) was implemented to classify 20 well-defined reference minerals. In a second step the spectra data of undetermined minerals in rock samples were projected on the PCA models to identify these mineral species. Hereby the data sets of positive and negative ion signals were used separately. It was possible to classify the reference minerals and identify mineral species in rock samples. Furthermore it was found that minerals not contained in the reference set were not misidentified.

Enhancing non-refractory aerosol apportionment from an urban industrial site through receptor modeling of complete high time-resolution aerosol mass spectra

Abstract. Receptor modeling was performed on quadrupole unit mass resolution aerosol mass spectrometer (Q-AMS) sub-micron particulate matter (PM) chemical speciation measurements from Windsor, Ontario, an industrial city situated across the Detroit River from Detroit, Michigan. Aerosol and trace gas measurements were collected on board Environment Canada's Canadian Regional and Urban Investigation System for Environmental Research (CRUISER) mobile laboratory. Positive matrix factorization (PMF) was performed on the AMS full particle-phase mass spectrum (PMFFull MS) encompassing both organic and inorganic components. This approach compared to the more common method of analyzing only the organic mass spectra (PMFOrg MS). PMF of the full mass spectrum revealed that variability in the non-refractory sub-micron aerosol concentration and composition was best explained by six factors: an amine-containing factor (Amine); an ammonium sulfate- and oxygenated organic aerosol-containing factor (Sulfate-OA); an ammonium nitrate- and oxygenated organic aerosol-containing factor (Nitrate-OA); an ammonium chloride-containing factor (Chloride); a hydrocarbon-like organic aerosol (HOA) factor; and a moderately oxygenated organic aerosol factor (OOA). PMF of the organic mass spectrum revealed three factors of similar composition to some of those revealed through PMFFull MS: Amine, HOA and OOA. Including both the inorganic and organic mass proved to be a beneficial approach to analyzing the unit mass resolution AMS data for several reasons. First, it provided a method for potentially calculating more accurate sub-micron PM mass concentrations, particularly when unusual factors are present, in this case the Amine factor. As this method does not rely on a priori knowledge of chemical species, it circumvents the need for any adjustments to the traditional AMS species fragmentation patterns to account for atypical species, and can thus lead to more complete factor profiles. It is expected that this method would be even more useful for HR–ToF–AMS data, due to the ability to understand better the chemical nature of atypical factors from high-resolution mass spectra. Second, utilizing PMF to extract factors containing inorganic species allowed for the determination of the extent of neutralization, which could have implications for aerosol parameterization. Third, subtler differences in organic aerosol components were resolved through the incorporation of inorganic mass into the PMF matrix. The additional temporal features provided by the inorganic aerosol components allowed for the resolution of more types of oxygenated organic aerosol than could be reliably resolved from PMF of organics alone. Comparison of findings from the PMFFull MS and PMFOrg MS methods showed that for the Windsor airshed, the PMFFull MS method enabled additional conclusions to be drawn in terms of aerosol sources and chemical processes. While performing PMFOrg MS can provide important distinctions between types of organic aerosol, it is shown that including inorganic species in the PMF analysis can permit further apportionment of organics for unit mass resolution AMS mass spectra.

Prevention of a dangerous tendency in the presentation of the results of GC-MS identification

A dangerous tendency manifested in the presentation of the results of gas chromatographic (GC)–mass spectrometric (MS) identification of components of complex mixtures of organic compounds is discussed. The number of publications containing unacceptable identification results has been increasing, especially within the last few years. The main signs of this are the absence of correspondence between the orders of elution of identified compounds and the general principles of chromatographic retention, which is attributed to unreliable chemical origin of the analytes, reporting of incorrect chemical names, erroneous chromatographic retention indices (RIs), and so on. The most effective and most convenient criterion for revealing such errors is checking the order of chromatographic elution of analytes by comparison with reference or predicted RIs. The contemporary practice of presenting the results of GC-MS identification of constituents of complex multicomponent mixtures accepted in most journal publications involves listing the multitude of identified compounds, supplemented with minimal sets of analytical parameters. Besides the names of compounds (the use of trivial names is traditionally preferred), these sets most often include GC RIs or absolute retention times (tR) of analytes, supplemented sometimes by their molecular weights and the mass numbers of the most intense peaks in their mass spectra (reduced MS information). The complete mass spectra are presented rather seldom because of objective restrictions on the length of publications in most journals. Because of the last restriction, important auxiliary MS information, e.g., spectral library match values, is omitted rather often. If this restriction is avoided (like it is in reports, dissertations, etc.), the complete mass spectra can be presented not only in numerical form, but even in graphical form. The presentation of part of the data on the Internet in the form of socalled supplementary materials, as recommended in some journals, improves the possibilities to check the results presented. The practice of creating a database of GC RIs [1–3] implies the search for retention data in all available literature sources. The main part of this work is the careful evaluation of data reliability, followed by revealing and excluding suspicious and/or erroneous RIs. The highly “compressed” form in which the results of GC-MS identification are presented in the current literature implies special demands be placed on their correctness. In connection with this, the appearance of a dangerous tendency of presenting unacceptable results of GC-MS identification should be taken into account. Unfortunately, the number of publications that are “suspicious” in relation to this tendency has been rising quickly, especially during the last few years. The aim of this communication is (1) to fix this tendency and (2) to discuss its possible reasons and consequences. Some simple rules are proposed to reveal the errors in the presentation of the results of GC-MS identification of constituents of complex mixtures and/or how to avoid them.