This review presents a comprehensive update on the state-of-the-art of nanometer-sized materials in solid-phase extraction (SPE) of trace elements followed by atomic-spectrometry detection. Zero-dimensional nanomaterials (fullerene), one-dimensional nanomaterials (carbon nanotubes, inorganic nanotubes, and nanowires), two-dimensional nanomaterials (nanofibers), and three-dimensional nanomaterials (nanoparticles, mesoporous nanoparticles, magnetic nanoparticles, and dendrimers) for SPE are discussed, with their application for trace-element analysis and their speciation in different matrices. A variety of other novel SPE sorbents, including restricted-access sorbents, ion-imprinted polymers, and metal–organic frameworks, are also discussed, although their applications in trace-element analysis are relatively scarce so far.
Nucleotides, their analogues, and other phosphate esters and phosphoramidates often contain the triethylammonium cation as a counterion. We found that this may be lost during chromatographic purification or concentration of solutions, yielding products in acidic forms or containing sub-stoichiometric amounts of the counterion. This in turn may be detrimental, e.g., due to possible decomposition of a compound or inaccurate sample preparation. Correlations between the structure of studied compounds and their susceptibility for cation loss were analyzed. Modifications in preparative techniques were developed to obtain the studied compounds with stoichiometric anion to cation ratios.
Graphical Abstract Triethylammonium salts of phosphate esters and phosphoramidates may lose the cationic component during chromatography or evaporation of solvent
Atmospheric aerosol particles of primary or secondary, biogenic or anthropogenic origin are highly complex samples of changing composition in time and space. To assess their effects on climate or human health, the size-dependent chemical composition of these ubiquitous atmospheric constituents must be known. The development of novel analytical methods has enabled more detailed characterization of the organic composition of aerosols. This review gives an overview of the methods used in the chemical characterization of atmospheric aerosol particles, with a focus on mass-spectrometry techniques for organic compounds, either alone or in combination with chromatographic separation. Off-line, on-site, and on-line methods are covered, and the advantages and limitations of the different methods are discussed. The main emphasis is on methods used for detailed characterization of the composition of the organic compounds in aerosol particles. We address and summarize the current state of analytical methods used in aerosol research and discuss the importance of developing novel sampling strategies and analytical instrumentation.
This study aims at evaluating the capabilities of synchrotron radiation micro X-ray fluorescence spectrometry (SR micro-XRF) for qualitative and semi-quantitative elemental mapping of the distribution of actinides in human tissues originating from individuals with documented occupational exposure. The investigated lymph node tissues were provided by the United States Transuranium and Uranium Registries (USTUR) and were analyzed following appropriate sample pre-treatment. Semi-quantitative results were obtained via calibration by external standards and demonstrated that the uranium concentration level in the detected actinide hot spots reaches more than 100 μg/g. For the plutonium hot spots, concentration levels up to 31 μg/g were found. As illustrated by this case study on these unique samples, SR micro-XRF has a high potential for this type of elemental bio-imaging owing to its high sensitivity, high spatial resolution, and non-destructive character.
Graphical Abstract SR micro-XRF study of the distribution of actinitides in human tissues. Left Location of the U-contaminated tissue sample in the human body. Middle U distribution derived from the high resolution SR micro-XRF scan on the tissue sample, indication of five U hot spots. Right Detail of the point measurement spectrum of U hot spot 3, intense U-Lα fluorescence peak located at 13.6 keV.
Cisplatin is a commonly used chemotherapeutic drug in cancer treatment, whereas Gd@C82(OH)22 is a new nanomaterial anti-tumor agent. In this study, we determined intracellular Gd@C82(OH)22 and cisplatin after treatment of Hela and 16HBE cells by single cell inductively coupled plasma-mass spectrometry (SC-ICP-MS), which could provide quantitative information at a single-cell level. The cell digestion method validated the accuracy of the SC-ICP-MS. The concentrations of Gd@C82(OH)22 and cisplatin in cells at different exposure times and doses were studied. The SC-ICP-MS is a promising complement to available methods for single cell analysis and is anticipated to be applied further to biomedical research.
Two-dimensional Fourier transform ion cyclotron resonance mass spectrometry (2D FT-ICR MS) allows data-independent fragmentation of all ions in a sample and correlation of fragment ions to their precursors through the modulation of precursor ion cyclotron radii prior to fragmentation. Previous results show that implementation of 2D FT-ICR MS with infrared multi-photon dissociation (IRMPD) and electron capture dissociation (ECD) has turned this method into a useful analytical tool. In this work, IRMPD tandem mass spectrometry of calmodulin (CaM) has been performed both in one-dimensional and two-dimensional FT-ICR MS using a top-down and bottom-up approach. 2D IRMPD FT-ICR MS is used to achieve extensive inter-residue bond cleavage and assignment for CaM, using its unique features for fragment identification in a less time- and sample-consuming experiment than doing the same thing using sequential MS/MS experiments.
Bisphenol A (BPA) is a synthetic chemical extensively used in many consumer products. It mimics estrogen activities and is related to developmental disorders and metabolic diseases. The current challenge of BPA detection is their low circulating levels at 0.1～10 ng/mL which is close to the detection limit of most of current analytical methods. In this report, we developed a simple, sensitive, and accurate liquid chromatography mass spectrometry (LCMS) method after 1-methylimidazole-2-sulfonyl chloride derivatization. The method significantly improves sensitivity 5～9-fold over dansyl derivatization and approximately 100-fold without derivatization.
Förster resonance energy transfer-based analytical techniques represent a unique tool for bioanalysis because they allow one to detect protein–protein interactions and conformational changes of biomolecules at the nanometer scale, both “in vitro” and “in vivo” in cells, tissues and organisms. These techniques are applied in diverse fields, from the detection and quantification of ligands able to bind to proteins or receptors to the development of RET-based whole-cell biosensors, microscope imaging techniques and “in vivo” whole-body imaging for the monitoring of physiological and pathological processes. However, their quantitative performances need further improvements and, even though RET measurement principles and procedures have been continuously improved, in some cases only qualitative or semiquantitative information can be obtained. In this review we report recent applications of RET-based analytical techniques and discuss their advantages and limitations.
Analyzing mass spectrometry imaging data can be laborious and time consuming, and as the size and complexity of datasets grow, so does the need for robust automated processing methods. We here present a method for comprehensive, semi-targeted discovery of molecular distributions of interest from mass spectrometry imaging data, using widely available image similarity scoring algorithms to rank images by spatial correlation. A fast and powerful batch search method using a MATLAB implementation of structural similarity (SSIM) index scoring with a pre-selected reference distribution is demonstrated for two sample imaging datasets, a plant metabolite study using Artemisia annua leaf, and a drug distribution study using maraviroc-dosed macaque tissue.
This review reports on the application of charge density analysis in the field of crystal engineering, which is one of the most growing and productive areas of the entire field of crystallography.While methods to calculate or measure electron density are not discussed in detail, the derived quantities and tools, useful for crystal engineering analyses, are presented and their applications in the recent literature are illustrated. Potential developments and future perspectives are also highlighted and critically discussed.
Matrix assisted laser desorption ionization imaging mass spectrometry (MALDI-IMS) is a technique that has seen a sharp rise in both use and development. Despite this rapid adoption, there have been few thorough investigations into the actual physical mechanisms that underlie the acquisition of IMS images. We therefore set out to characterize the effect of IMS laser ablation patterns on the surface of a sample. We also concluded that the governing factors that control spatial resolution have not been correctly defined and therefore propose a new definition of resolution.
A hybrid of reduced graphene oxide–palladium (RGO–Pd) nano- to submicron-scale particles was simultaneously chemically prepared using microwave irradiation. The electrochemical investigation of the resulting hybrid was achieved using cyclic voltammetry and differential pulse voltammetry. RGO–Pd had a higher current response than unmodified RGO toward the oxidation of morphine. Several factors that can affect the electrochemical response were studied, including accumulation time and potential, Pd loading, scan rate, and pH of electrolyte. At the optimum conditions, the concentration of morphine was determined using differential pulse voltammetry in a linear range from 0.34 to 12 μmol L?1 and from 14 to 100 μmol L?1, with detection limits of 12.95 nmol L?1 for the first range. The electrode had high sensitivity toward morphine oxidation in the presence of dopamine (DA) and of the interference compounds ascorbic acid (AA) and uric acid (UA). Electrochemical determination of morphine in a spiked urine sample was performed, and a low detection limit was obtained. Validation conditions including reproducibility, sensitivity, and recovery were evaluated successfully in the determination of morphine in diluted human urine.
High resolution mass spectrometry is a key technology for in-depth protein characterization. High-field Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) enables high-level interrogation of intact proteins in the most detail to date. However, an appropriate complement of fragmentation technologies must be paired with FTMS to provide comprehensive sequence coverage, as well as characterization of sequence variants, and post-translational modifications. Here we describe the integration of front-end electron transfer dissociation (FETD) with a custom-built 21 tesla FT-ICR mass spectrometer, which yields unprecedented sequence coverage for proteins ranging from 2.8 to 29 kDa, without the need for extensive spectral averaging (e.g., ~60% sequence coverage for apo-myoglobin with four averaged acquisitions). The system is equipped with a multipole storage device separate from the ETD reaction device, which allows accumulation of multiple ETD fragment ion fills. Consequently, an optimally large product ion population is accumulated prior to transfer to the ICR cell for mass analysis, which improves mass spectral signal-to-noise ratio, dynamic range, and scan rate. We find a linear relationship between protein molecular weight and minimum number of ETD reaction fills to achieve optimum sequence coverage, thereby enabling more efficient use of instrument data acquisition time. Finally, real-time scaling of the number of ETD reactions fills during method-based acquisition is shown, and the implications for LC-MS/MS top-down analysis are discussed.
High spatial resolution in mass spectrometry imaging (MSI) is crucial to understanding the biology dictated by molecular distributions in complex tissue systems. Here, we present MSI using infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) at 50 μm resolution. An adjustable iris, beam expander, and an aspherical focusing lens were used to reduce tissue ablation diameters for MSI at high resolution. The laser beam caustic was modeled using laser ablation paper to calculate relevant laser beam characteristics. The minimum laser spot diameter on the tissue was determined using tissue staining and microscopy. Finally, the newly constructed optical system was used to image hen ovarian tissue with and without oversampling, detailing tissue features at 50 μm resolution.
Although experimental design is a powerful tool, it is rarely used for the development of analytical methods for the determination of organic contaminants in the environment. When investigated factors are interdependent, this methodology allows studying efficiently not only their effects on the response but also the effects of their interactions. A complete and didactic chemometric study is described herein for the optimization of an analytical method involving stir bar sorptive extraction followed by thermal desorption coupled with gas chromatography and tandem mass spectrometry for the rapid quantification of several pesticides in freshwaters. We studied, under controlled conditions, the effects of thermal desorption parameters and the effects of their interactions on the desorption efficiency. The desorption time, temperature, flow, and the injector temperature were optimized through a screening design and a Box–Behnken design. The two sequential designs allowed establishing an optimum set of conditions for maximum response. Then, we present the comprehensive validation and the determination of measurement uncertainty of the optimized method. Limits of quantification determined in different natural waters were in the range of 2.5 to 50 ng L?1, and recoveries were between 90 and 104 %, depending on the pesticide. The whole method uncertainty, assessed at three concentration levels under intra-laboratory reproducibility conditions, was below 25 % for all tested pesticides. Hence, we optimized and validated a robust analytical method to quantify the target pesticides at low concentration levels in freshwater samples, with a simple, fast, and solventless desorption step.
Quantum dots (QDs) have a number of unique optical properties that are advantageous in the development of bioanalyses based on fluorescence resonance energy transfer (FRET). Researchers have used QDs as energy donors in FRET schemes for the analysis of nucleic acids, proteins, proteases, haptens, and other small molecules. This paper reviews these applications of QDs. Existing FRET technologies can potentially be improved by using QDs as energy donors instead of conventional fluorophores. Superior brightness, resistance to photobleaching, greater optimization of FRET efficiency, and/or simplified multiplexing are possible with QD donors. The applicability of the Förster formalism to QDs and the feasibility of using QDs as energy acceptors are also reviewed.
With the rapid growth of therapeutic monoclonal antibodies (mAbs), stringent quality control is needed to ensure clinical safety and efficacy. Monoclonal antibody primary sequence and post-translational modifications (PTM) are conventionally analyzed with labor-intensive, bottom-up tandem mass spectrometry (MS/MS), which is limited by incomplete peptide sequence coverage and introduction of artifacts during the lengthy analysis procedure. Here, we describe top-down and middle-down approaches with the advantages of fast sample preparation with minimal artifacts, ultrahigh mass accuracy, and extensive residue cleavages by use of 21 tesla FT-ICR MS/MS. The ultrahigh mass accuracy yields an RMS error of 0.2–0.4 ppm for antibody light chain, heavy chain, heavy chain Fc/2, and Fd subunits. The corresponding sequence coverages are 81%, 38%, 72%, and 65% with MS/MS RMS error ~4 ppm. Extension to a monoclonal antibody in human serum as a monoclonal gammopathy model yielded 53% sequence coverage from two nano-LC MS/MS runs. A blind analysis of five therapeutic monoclonal antibodies at clinically relevant concentrations in human serum resulted in correct identification of all five antibodies. Nano-LC 21 T FT-ICR MS/MS provides nonpareil mass resolution, mass accuracy, and sequence coverage for mAbs, and sets a benchmark for MS/MS analysis of multiple mAbs in serum. This is the first time that extensive cleavages for both variable and constant regions have been achieved for mAbs in a human serum background.
Mass defect is associated with the binding energy of the nucleus. It is a fundamental property of the nucleus and the principle behind nuclear energy. Mass defect has also entered into the mass spectrometry terminology with the availability of high resolution mass spectrometry and has found application in mass spectral analysis. In this application, isobaric masses are differentiated and identified by their mass defect. What is the relationship between nuclear mass defect and mass defect used in mass spectral analysis, and are they the same?
Recombinant human follicle stimulating hormone is an important drug in reproductive medicine. Thorough analysis of the heterodimeric heavily glycosylated protein is a prerequisite for the evaluation of production batches as well as for the determination of “essential similarity” of new biosimilars. The concerted application of different liquid chromatography-mass spectrometry methods enabled the complete depiction of the primary structure of this pituitary hormone. Sequence coverage of 100% for the α- as well as the β-chain was achieved with tryptic peptides. Most of these peptides could be verified by tandem mass spectrometry. Site-specific analysis of all four glycosylation sites was, however, not possible with tryptic but with chymotryptic peptides. Quantification of the glycoforms of each glycopeptide was accomplished with the software MassMap®. Both protein subunits gave interpretable mass spectra upon S-alkylation and separation on a C5 reversed-phase column. Glycan isomer patterns were depicted by separation on porous graphitic carbon, using mass spectrometric detection for the evaluation of the glycopeptide liquid chromatography-electrospray ionization data. The currently marketed product Gonal-f? and a potential biosimilar were compared with the help of these procedures.
Figure Schematic depiction of the glycoprotein nature of human follicle-stimulating hormone with the alfa chain in blue and the beta chain in purple and a mass spectrum of the alfa chain at the bottom.
Matrix-assisted laser/desorption ionization (MALDI) mass spectrometry imaging (MSI) is widely used as a unique tool to record the distribution of a large range of biomolecules in tissues. 2,6-Dihydroxyacetophenone (DHA) matrix has been shown to provide efficient ionization of lipids, especially gangliosides. The major drawback for DHA as it applies to MS imaging is that it sublimes under vacuum (low pressure) at the extended time necessary to complete both high spatial and mass resolution MSI studies of whole organs. To overcome the problem of sublimation, we used an atmospheric pressure (AP)-MALDI source to obtain high spatial resolution images of lipids in the brain using a high mass resolution mass spectrometer. Additionally, the advantages of atmospheric pressure and DHA for imaging gangliosides are highlighted. The imaging of [M–H]? and [M–H2O–H]? mass peaks for GD1 gangliosides showed different distribution, most likely reflecting the different spatial distribution of GD1a and GD1b species in the brain.
