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Currently, all assays measuring acetylcholinesterase (AChE) activity following a suspected nerve agent exposure leverage methodologies that fail to identify the agent. This limits the overall effectiveness and ability to administer proper countermeasures. As such, there is an urgent need to identify novel, rapid, and more comprehensive approaches to establish AChE activity, including identification of the toxicant. Paper spray mass spectrometry was used to monitor the activity of acetylcholinesterase, both in-solution and on modified hydrophobic paper surface. Hydrophobic paper surfaces were prepared using vaporized trichloro(3,3,3-trifluoropropyl)silane. In both approaches, mixtures of diluted human whole blood with and without VX were mixed with a non-endogenous AChE specific substrate, 1,1-dimethyl-4-acetylthiomethylpiperidinium (MATP+). Formation of the cleaved MATP+ product was monitored over time and compared to MATP+ to determine relative AChE activity. This on-substrate assay was effective at determining AChE activity and identifying the toxicant; however, determination of AChE activity in-solution proceeded at a slower rate. The on-substrate assay serves as a pioneering example of an enzymatic reaction occurring on the surface of a paper spray ionization ticket. This work broadens the range of applications relating to paper spray ionization-based clinical diagnostic assays. Graphical Abstract ᅟ.

The ability to detect atmospheric effluent from clandestine methamphetamine manufacture is a useful tool for law enforcement. A membrane inlet mass spectrometer is mounted onto an all-electric drive capable hybrid vehicle that samples the atmosphere while in motion. Attributing a latitude and longitude to each spectrum collected, unique chemical fingerprints from clandestine manufacture are then mapped. This location-based mass spectrum data provides a localization to an area of interest. The synthesis of methamphetamine precursors was performed, and the impurities from such reactions were observed. A mock manufacture was setup, and the impurities were introduced into the atmosphere via heating. The detection of products and impurities using this mobile platform has shown the effectiveness of locating and localizing the manufacture of methamphetamine.

Field-forward analytical technologies, such as portable mass spectrometry (MS), enable essential capabilities for real-time monitoring and point-of-care diagnostic applications. Significant and recent investments improving the features of miniaturized mass spectrometers enable various new applications outside of small molecule detection. Most notably, the addition of tandem mass spectrometry scans (MS/MS) allows the instrument to isolate and fragment ions and increase the analytical specificity by measuring unique chemical signatures for ions of interest. Notwithstanding these technological advancements, low-cost, portable systems still struggle to confidently identify clinically significant organisms of interest, such as bacteria, viruses, and proteinaceous toxins, due to the limitations in resolving power. To overcome these limitations, we developed a novel multidimensional mass fingerprinting technique that uses tandem mass spectrometry to increase the chemical specificity for low-resolution mass spectral profiles. We demonstrated the method's capabilities for differentiating four different bacteria, including attentuated strains of Yersinia pestis. This approach allowed for the accurate (>92%) identification of each organism at the strain level using de-resolved matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) data to mimic the performance characteristics of miniaturized mass spectrometers. This work demonstrates that low-resolution mass spectrometers, equipped with tandem MS acquisition modes, can accurately identify clinically relevant bacteria. These findings support the future application of these technologies for field-forward and point-of-care applications where high-performance mass spectrometers would be cost-prohibitive or otherwise impractical. [ABSTRACT FROM AUTHOR]

We present an analysis of ambient benzene, toluene, and xylene isomers in the Eagle Ford shale region of southern Texas. In situ air quality measurements using membrane inlet mobile mass spectrometry revealed ambient benzene and toluene concentrations as high as 1000 and 5000 parts-per-billion, respectively, originating from specific sub-processes on unconventional oil and gas well pad sites. The detection of highly variant contamination events attributable to natural gas flaring units, condensate tanks, compressor units, and hydrogen sulfide scavengers indicates that mechanical inefficiencies, and not necessarily the inherent nature of the extraction process as a whole, result in the release of these compounds into the environment. This awareness of ongoing contamination events contributes to an enhanced knowledge of ambient volatile organic compounds on a regional scale. While these reconnaissance measurements on their own do not fully characterize the fluctuations of ambient BTEX concentrations that likely exist in the atmosphere of the Eagle Ford Shale region, they do suggest that contamination events from unconventional oil and gas development can be monitored, controlled, and reduced. [ABSTRACT FROM AUTHOR]

The cover image is based on the Research Article On‐Substrate Derivatization for Highly Volatile G‐Series Chemical Warfare Agent Detection via Paper Spray Mass Spectrometry by Phillip M. Mach et al., https://doi.org/10.1002/rcm.8276. [ABSTRACT FROM AUTHOR]

Proteinaceous toxins are harmful proteins derived from plants, bacteria, and other natural sources. They pose a risk to human health due to infection and also as possible biological warfare agents. Paper spray mass spectrometry (PS-MS) with wipe sampling was used to detect proteins from surfaces as a potential tool for identifying the presence of these toxins. Proteins ranging in mass between 12.4 and 66.5 kDa were tested, including a biological toxin simulant/vaccine for Staphylococcal enterotoxin B (SEBv). Various substrates were tested for these representative proteins, including a laboratory bench, a notebook cover, steel, glass, plant leaf and vinyl flooring. Carbon sputtered porous polyethylene (CSPP) was found to outperform typical chromatography paper used for paper spray, as well as carbon nanotube (CNT)-coated paper and polyethylene (PE), which have been previously shown to be well-suited for protein analysis. Low microgram quantities of the protein toxin simulant and other test proteins were successfully detected with good signal-to-noise from surfaces using a porous wipe. These applications demonstrate that PS-MS can potentially be used for rapid, sample preparation-free detection of proteins and biological warfare agents, which would be beneficial to first responders and warfighters. [ABSTRACT FROM AUTHOR]

Mass spectrometry based 'omics pairs well with organ-on-a-chip-based investigations, which often have limited cellular material for sampling. However, a common issue with these chip-based platforms is well-to-well or chip-to-chip variability in the proteome and metabolome due to factors such as plate edge effects, cellular asynchronization, effluent flow, and limited cell count. This causes high variability in the quantitative multi-omics analysis of samples, potentially masking true biological changes within the system. Solutions to this have been approached via data processing tools and post-acquisition normalization strategies such as constant median, constant sum, and overall signal normalization. Unfortunately, these methods do not adequately correct for the large variations, resulting in a need for increased biological replicates. The methods in this work utilize a dansylation based assay with a subset of labeled metabolites that allow for pre-acquisition normalization to better correlate the biological perturbations that truly occur in chip-based platforms. BCA protein assays were performed in tandem with a proteomics pipeline to achieve pre-acquisition normalization. The CN Bio PhysioMimix was seeded with primary hepatocytes and challenged with VX after six days of culture, and the metabolome and proteome were analyzed using the described normalization methods. A decreased coefficient of variation percentage is achieved, significant changes are observed through the proteome and metabolome, and better classification of biological replicates acquired because of these strategies. [Display omitted] • Organ-on-a-chips are becoming more prevalent. • Organs-on-a-chip display a wide variation in 'omic analysis. • For metabolmic analysis there is a need for pre-acquisition normalization. • Danyslation normalization works well for normalizing organ-on-a-chip samples. [ABSTRACT FROM AUTHOR]

Chemical warfare agents (CWAs) are devastating weapons of terror due to their highly lethal and dispersive nature. Powerful analytical tools are required to help create a knowledge base that will contribute to preventing attacks using these agents. Highly sensitive measurements must be made quickly with high selectivity for a wide range of potential molecular targets. Portable mass spectrometers have emerged as a robust platform for in-situ detection of chemical threats. However, due to size, weight, and power constraints, they are typically limited to a single mass analyzer with limited MS/MS capabilities, most notably the provision of full scan and product ion MS/MS spectra. Here we demonstrate the application of a new, highly efficient scanning methodology that uses a single linear quadrupole ion trap to acquire two-dimensional mass spectrometry data (2D MS/MS). With only a single scan, we show that it is possible to acquire mass-to-charge information on V-series chemical warfare agents– namely,: (1) Ethyl ({2-[bis(propan-2-yl)amino]ethyl}sulfanyl)(methyl)phosphinate (V1), (2) N , N -diethyl-2-(methyl-(2-methylpropoxy)phosphoryl)sulfanylethanamine (VR), (3) O-Butyl S-[2-(diethylamino)ethyl] methylphosphonothioate (VX) and (4) S-[2-(Diethylamino)ethyl] O-ethyl methylphosphonothioate (VM) - as precursors while simultaneously (in the same scan) acquiring product ion spectra for each CWA via mass spectral microfeatures. For mixtures of V-series agents, 2D MS/MS is a time- and sample-efficient method for obtaining MS/MS data. Discussed here are advantages and limitations of 2D MS/MS compared to conventional data-dependent product ion MS/MS scans. Image 1 • Detection of V series chemical warfare agents using 2D MS/MS. • Comparison of 2D MS/MS with conventional product ion MS/MS on a linear ion trap. • Differentiation of isobaric species via unique 2D MS/MS patterns. [ABSTRACT FROM AUTHOR]