Correction: Paper spray mass spectrometry utilizing Teslin® substrate for rapid detection of lipid metabolite changes during COVID-19 infection.

Correction for 'Paper spray mass spectrometry utilizing Teslin® substrate for rapid detection of lipid metabolite changes during COVID-19 infection' by Imesha W. De Silva et al., Analyst, 2020, 145, 5725-5732, DOI: 10.1039/D0AN01074J.

Inhalation exposure to silver nanoparticles induces hepatic inflammation and oxidative stress, associated with altered renin-angiotensin system signaling, in Wistar rats.

Silver nanoparticles (AgNPs) have become increasingly popular in the biomedical field over the last few decades due to its proven antibacterial property. Previous scientific studies have reported that one of the major organs responsible for detoxification of AgNPs is the liver. The liver is also the primary organ responsible for secretion of angiotensinogen (AGT), a key signaling molecule involved in the renin-angiotensin system (RAS), which plays an important role in maintaining cardiac output and vascular pressure. The aim of this study was to assess any potential changes in the RAS-associated gene signaling, inflammatory response, and hepatocellular toxicity resulting from AgNP exposure. To do this, 6-week-old, male Wistar rats were exposed to a subacute inhalation exposure of AgNP (200 ppb/days over 4 h/days exposure, for 5 d) and their livers were analyzed for alterations in RAS components, inflammation, and oxidative stress. Real time qPCR analysis showed that AgNP-exposure resulted in a significant increase in hepatic AGT, angiotensin converting enzyme (ACE)-1, and ACE-2 mRNA expression. Expression of inflammatory markers interleukin (IL)-6, IL-1ß, and tumor necrosis factor (TNF)-α were also upregulated with AgNP-exposure, compared to controls. Furthermore AgNP-exposure mediated a significant increase in hepatic expression of catalase, and superoxide dismutase, and oxidative stress, as assessed via 8-Oxo-2'-deoxyguanosine staining. Increased oxidative stress was associated with increased monocyte/macrophage-2 staining in the liver of AgNP-exposed rats. Such findings indicate that subacute inhalation exposure to AgNPs mediate increased hepatic RAS signaling, associated with inflammation, macrophage infiltration, and oxidative stress.

Paper Spray Mass Spectrometry Utilized with a Synthetic Microporous Polyolefin Silica Matrix Substrate in the Rapid Detection and Identification of More than 190 Synthetic Fentanyl Analogs.

Fentanyl and its related synthetic analogs have recently become more readily available as a growing threat to public safety, such as pain relief and anesthetics. Sources of fentanyl are more likely to be illicitly manufactured than pharmaceutically manufactured and are often laced with other opioids, which ultimately increases the potency of fentanyl and results in an increased number of overdose deaths. The methods used to detect these compounds safely and quickly are of high interest due to their extreme potency. This study investigates the use of paper spray mass spectrometry (PS-MS), which is a simple atmospheric ionization process that can be used as a rapid study (60 s) with limited sample preparation and sample handling. PS-MS can be utilized with a synthetic microporous polyolefin silica matrix substrate, known as Teslin, which is manufactured by PPG Industries. The main characteristic of paper spray ionization with the Teslin substrate is the hydrophobicity, which is useful for a fast and direct analysis requiring only 1 µg of the sample. The application of this novel synthetic substrate to PS-MS has been illustrated with a fentanyl analog screening kit (FAS Kit), which was designed by the Centers for Disease Control (CDC) for the screening of 212 evolving synthetic opioids, including more than 190 fentanyl analogs. The comparable fragmentation with precursor molecule mass data from this study can be useful in improving the accurate detection and structural characterization of complex samples with a minimum interference of the isobaric components.

Toxicological alterations induced by subacute exposure of silver nanoparticles in Wistar rats.

Silver nanoparticles (AgNPs) have become crucial players in the field of medicine and various other industries. AgNPs have a wide array of applications, which includes production of electronic goods, cosmetics, synthesis of dyes, and printing inks, as well as targeted delivery of drugs to specialized cells inside the body. Even though humans readily come in contact with these particles, the organ-specific accumulation and resulting mechanisms of toxicity induced by inhaled AgNPs are still under investigation. The goal of this study was to determine the organ distribution of inhaled AgNPs and investigate the resulting systemic toxicity. To do this, male Wistar rats were exposed by inhalation to AgNPs for 4 hr/day (200 parts per billion/day) for five consecutive days. The nanoparticles were generated using a laser ablation technique using a soft-landing ion mobility (SLIM) instrument. Inductively coupled plasma mass spectrometric (ICP-MS) analysis showed organ-specific accumulation of the nanoparticles, with the highest concentration present in the lungs, followed by the liver and kidneys. Nanoparticle distribution was characterized in the organs using scanning electron microscopy (SEM) and matrix-assisted laser desorption/ionization mass spectrometric (MALDI-MS) imaging. Bone marrow cytotoxicity assay of the cells from the femur of rats showed micronuclei formation and signs of cellular cytotoxicity. Moreover, rats displayed increased levels of circulating lactate and glutathione disulphide (GSSG), as determined by liquid chromatography-mass spectrometry (LC-MS) analysis. Collectively, our observations suggest that inhaled subacute exposure to AgNP results in accumulation of AgNPs in the lungs, liver, and kidneys, preferentially, as well as mediates induced systemic toxicity.

Effects of crude oil vapors on the cardiovascular flow of embryonic Gulf killifish.

Direct contact with toxicants in crude oil during embryogenesis causes cardiovascular defects, but the effects of exposure to airborne volatile organic compounds released from spilled oil are not well understood. The effects of crude oil-derived airborne toxicants on peripheral blood flow were examined in Gulf killifish (Fundulus grandis) since this model completes embryogenesis in the air. Particle image velocimetry was used to measure in vivo blood flow in intersegmental arteries of control and oil-exposed embryos. Significant effects in oil-exposed embryos included increased pulse rate, reduced mean blood flow speed and volumetric flow rate, and decreased pulsatility, demonstrating that normal-appearing oil-exposed embryos retain underlying cardiovascular defects. Further, hematocrit moderately increased in oil-exposed embryos. This study highlights the potential for fine-scale physiological measurement techniques to better understand the sub-lethal effects of oil exposure and demonstrates the efficacy of Gulf killifish as a unique teleost model for aerial toxicant exposure studies.

Metallic nanoparticle production and exposure/deposition system for toxicological research applications using zebrafish.

Metallic nanoparticles (NPs) have been accepted for various applications ranging from cosmetics to medicine. However, no method has been established in the scientific community that is capable of analyzing various metals, sizes, and levels of exposures without the concern of background chemical contaminations. We present here a system utilizing soft-landing ion mobility (SLIM) exposures of laser ablated metallic clusters capable of operating pressures of reduced vacuum (1 Torr) up to ambient (760 Torr) in the presence of a buffer gas. Clusters experience kinetic energies of less than 1 eV upon exiting the SLIM, allowing for the exposure of NPs to take place in a passive manner. While there is no mass-selection of cluster sizes in this work, it does show for the first time the creation and soft-landing of nanoclusters at ambient pressures. Factors such as area coverage and percentage distribution were studied, as well as the different effects that varying surfaces may cause in the agglomeration of the clusters. Furthermore, the system was successfully used to study the effects of silver nanoparticle exposure and determine the specific organs the NPs accumulate in using zebrafish (Danio rerio) as a model organism. This method provides a novel way to synthesize NPs and expose biological organisms for various toxicological analysis.

Paper spray mass spectrometry utilizing Teslin® substrate for rapid detection of lipid metabolite changes during COVID-19 infection.

The SARS-CoV-2 virus is known as the causal agent for the current COVID-19 global pandemic. The majority of COVID-19 patients develop acute respiratory distress syndrome (ARDS), while some experience a cytokine storm effect, which is considered as one of the leading causes of patient mortality. Lipids are known to be involved in the various stages of the lifecycle of a virus functioning as receptors or co-receptors that controls viral propagation inside the host cell. Therefore, lipid-related metabolomics aims to provide insight into the immune response of the novel coronavirus. Our study has focused on determination of the potential metabolomic biomarkers utilizing a Teslin® Substrate in paper spray mass spectrometry (PS-MS) for the development of a rapid detection test within 60 seconds of analysis time. In this study, results were correlated with PCR tests to reflect that the systemic responses of the cells were affected by the COVID-19 virus.

The genome of jojoba (Simmondsia chinensis): A taxonomically isolated species that directs wax ester accumulation in its seeds.

Seeds of the desert shrub, jojoba (Simmondsia chinensis), are an abundant, renewable source of liquid wax esters, which are valued additives in cosmetic products and industrial lubricants. Jojoba is relegated to its own taxonomic family, and there is little genetic information available to elucidate its phylogeny. Here, we report the high-quality, 887-Mb genome of jojoba assembled into 26 chromosomes with 23,490 protein-coding genes. The jojoba genome has only the whole-genome triplication (γ) shared among eudicots and no recent duplications. These genomic resources coupled with extensive transcriptome, proteome, and lipidome data helped to define heterogeneous pathways and machinery for lipid synthesis and storage, provided missing evolutionary history information for this taxonomically segregated dioecious plant species, and will support efforts to improve the agronomic properties of jojoba.

Synthetic route sourcing of illicit at home cannabidiol (CBD) isomerization to psychoactive cannabinoids using ion mobility-coupled-LC-MS/MS.

This study focuses on the chemical route sourcing of illicitly produced Δ9-Tetrahydrocannabinol (Δ9-THC) via the acid-catalyzed cannabidiol isomerization reaction. Each of the acid-catalyzed reactions used acids that are readily available for the general population such as battery acid, muriatic acid, and vinegar. After the acid-catalyzed isomerization was complete, an analysis using Liquid Chromatography-coupled-Mass Spectrometry (LC-MS)-coupled-ion mobility to confirm all synthetic impurities in the sample was conducted. The conducted chemical route sourcing allows law enforcement to be able to determine how CBD was converted to psychoactive cannabinoids. Specifically, 10-methoxy-THC, 11-hydroxy-THC, 11,5″-dihydroxy-Δ9-THC, and 5″-hydroxy-CBD were able to be used as indicators in the determination of the chemical route sourcing. Additionally, the ion mobility allowed for a rapid secondary separation of the psychoactive cannabinoids without the need for the long LC/MS analysis time.

Analysis of Lipids in Single Cells and Organelles Using Nanomanipulation-Coupled Mass Spectrometry.

The ability to discriminately analyze the chemical constituents of single cells and organelles is highly sought after and necessary to establish true biomarkers. Some major challenges of individual cell analysis include requirement and expenditure of a large sample of cells as well as extensive extraction and separation techniques. Here, we describe methods to perform individual cell and organelle extractions of both tissues and cells in vitro using nanomanipulation coupled to mass spectrometry. Lipid profiles display heterogeneity from extracted adipocytes and lipid droplets, demonstrating the necessity for single cell analysis. The application of these techniques can be applied to other cell and organelle types for selective and thorough monitoring of disease progression and biomarker discovery.

Nanoextraction Coupled to Liquid Chromatography Mass Spectrometry Delivers Improved Spatially Resolved Analysis.

Direct analyte-probed nanoextraction (DAPNe) is a technique that allows extraction of drug and endogenous compounds from a discrete location on a tissue sample using a nano capillary filled with solvent. Samples can be extracted from spot diameters as low as 6 µm. Studies previously undertaken by our group have shown that the technique can provide good precision (5%) for analyzing drug molecules in 150 µm diameter areas of homogenized tissue, provided an internal standard is sprayed on to the tissue prior to analysis. However, without an isotopically labeled standard, the repeatability is poor, even after normalization to the spot area or matrix compounds. By application to tissue homogenates spiked with drug compounds, we can demonstrate that it is possible to significantly improve the repeatability of the technique by incorporating a liquid chromatography separation step. Liquid chromatography is a technique for separating compounds prior to mass spectrometry (LC-MS) which enables separation of isomeric compounds that cannot be discriminated using mass spectrometry alone, as well as reducing matrix interferences. Conventionally, LC-MS is carried out on bulk or homogenized samples, which means analysis is essentially an average of the sample and does not take into account discrete areas. This work opens a new opportunity for spatially resolved liquid chromatography mass spectrometry with precision better than 20%.

True one cell chemical analysis: a review.

The constantly growing field of True One Cell (TOC) analysis has provided important information on the direct chemical composition of various cells and cellular components. Since the heterogeneity of individual cells has been established, more researchers are interested in the chemical differences between individual cells; TOC is the only form of analysis that can provide this information. This has resulted in the constant development of new technologies and methods. This review highlights the common techniques for micro- and nanomanipulation, Raman spectroscopy, microscopy, and mass spectrometric imaging as they pertain to TOC chemical analysis.

Generation of transgenic zebrafish with 2 populations of RFP- and GFP-labeled thrombocytes: analysis of their lipids.

Zebrafish thrombocytes are similar to mammalian platelets. Mammals have young platelets (also called reticulated platelets) and mature platelets. Likewise, zebrafish have 2 populations of thrombocytes; one is DiI-C18 (DiI)+ (DP), and the other is DiI- (DN). However, the mechanism of selective thrombocyte labeling by DiI is unknown. Furthermore, there is no transgenic zebrafish line where DP and DN thrombocytes are differentially labeled with fluorescent proteins. In this study, we found that Glo fish, in which the myosin light chain 2 promoter drives the rfp gene, have a population of thrombocytes that are red fluorescent protein (RFP) labeled. We also generated transgenic GloFli fish in which DP and DN thrombocytes are labeled with RFP and green fluorescent protein (GFP), respectively. Single-cell lipid analysis showed a twofold increase in phosphatidylethanolamine (PE) and a twofold decrease in phosphatidylcholine (PC) in RFP+ thrombocytes compared with GFP+ thrombocytes, suggesting that lipid composition may be important for DiI differential labeling. Therefore, we tested liposomes prepared with different ratios of PC and PE and observed that liposomes prepared with higher amounts of PE favor DiI labeling, whereas the PC concentration had a modest effect. In liposomes prepared using only PE or PC, increased concentrations of PE resulted in increased DiI binding. These results suggest that because RFP+ thrombocytes have higher PE concentrations, DiI may bind to them efficiently, thus explaining the selective labeling of thrombocytes by DiI. This work also provides GloFli fish that should be useful in understanding the mechanism of thrombocyte maturation.

A Mass Spectrometer in Every Fume Hood.

Since their inception, mass spectrometers have played a pivotal role in the direction and application of synthetic chemical research. The ability to develop new instrumentation to solve current analytical challenges in this area has always been at the heart of mass spectrometry, although progress has been slow at times. Herein, we briefly review the history of how mass spectrometry has been used to approach challenges in organic chemistry, how new developments in portable instrumentation and ambient ionization have been used to open novel areas of research, and how current techniques have the ability to expand on our knowledge of synthetic mechanisms and kinetics. Lastly, we discuss the relative paucity of work done in recent years to embrace the concept of improving benchtop synthetic chemistry with mass spectrometry, the disconnect between applications and fundamentals within these studies, and what hurdles still need to be overcome. Graphical Abstract.

Investigation by direct-infusion ESI-MS and GC-MS of an alleged Leuckart route-specific impurity of methamphetamine.

Impurity profiling has been used as a useful tool for analyzing nearly every drug class currently known on the illicit market. Impurities present within seized samples have the potential to determine source of origin, route of synthesis used, as well as provide a useful clue into the potential reaction mechanisms that are present for each synthetic procedure. Perhaps the most well studied of these impurity profiles exists for methamphetamine, including information to more than one route of synthesis. Within the present study, a complete synthesis of methamphetamine was performed, including a reductive amination of phenylpropanone (P2P) using methylamine hydrochloride and sodium triacetoxyborohydride (STAB) rather than the conventional aluminum mercury amalgam commonly found in the literature. During the analysis of the final product from this reaction, a major impurity within the reaction, bis(1-phenylpropan-2-yl)amine (m/z 253), was detected by GC-MS as well as direct-infusion ESI-MS. This impurity has been previously reported as a Leuckart route-specific impurity. Its detection within the reductive amination of P2P points towards the use of impure methylamine hydrochloride containing some traces of acid, and provides further insight into the reductive amination of P2P. In both the Leuckart reaction and this reductive amination via STAB, the presence of acid and ammonia leads to this impurity.

DAPNe with micro-capillary separatory chemistry-coupled to MALDI-MS for the analysis of polar and non-polar lipid metabolism in one cell.

The cellular metabolome is considered to be a representation of cellular phenotype and cellular response to changes to internal or external events. Methods to expand the coverage of the expansive physiochemical properties that makeup the metabolome currently utilize multi-step extractions and chromatographic separations prior to chemical detection, leading to lengthy analysis times. In this study, a single-step procedure for the extraction and separation of a sample using a micro-capillary as a separatory funnel to achieve analyte partitioning within an organic/aqueous immiscible solvent system is described. The separated analytes are then spotted for MALDI-MS imaging and distribution ratios are calculated. Initially, the method is applied to standard mixtures for proof of partitioning. The extraction of an individual cell is non-reproducible; therefore, a broad chemical analysis of metabolites is necessary and will be illustrated with the one-cell analysis of a single Snu-5 gastric cancer cell taken from a cellular suspension. The method presented here shows a broad partitioning dynamic range as a single-step method for lipid analysis demonstrating a decrease in ion suppression often present in MALDI analysis of lipids. Graphical Abstract ᅟ.

Laser ablation coupled with DAPNe-NSI-MS applied to redacted documents.

Laser ablation has been applied to redacted documents, where the text has been concealed by other ink. This technique strips the redacting ink revealing the text that was once redacted. Once removed, a nanomanipulation technique is used to extract the ink of the underlying text where mass spectrometry is then implemented to analyze its ink chemistry. In order to facilitate microscopy with direct analyte-probed nanoextraction coupled to nanospray ionization mass spectrometry (DAPNe-NSI-MS), laser ablation must be executed prior to ink extraction. Laser ablation has a nondestructive approach of stripping the ink used to redact the document. Not only does this reveal the text, it clears an area for DAPNe to directly extract ink, in miniscule amounts, from the document without inducing destruction. The redacting ink was concluded to affect the aging process of the concealed handwritten ink more than the printed text. The redacted handwritten sample obtained higher relative peak area (%) values than the control samples (text that was not redacted) and the control for the printed text produced higher amounts of low molecular weight products than the sample. Implementing laser ablation on these samples could also affect the chemical properties of the underlying ink due to the additional UV radiation and plasma heating. Results indicate by using laser ablation to remove the redacting ink, the relative peak area of the underlying ink deviates by 1.25%. The thermal degradation of binding agents such as polymethylene, polyethylene glycol, and diethylene glycol was monitored by calculating the relative peak area for five days which, in turn, tracks the oxidation process. The relative peak area values were also used to determine the chemical kinetics of polyethylene glycol, where degradation and polymerization occur.

Analysis of trace amounts of adulterants found in powders/supplements utilizing Raman spectroscopy coupled to direct analyte-probed nanoextraction-nanospray ionization-mass spectrometry.

In the United States, all food products have to be regulated to inform the consumers of the ingredients contained within. Some ingredients are not included on the label and yet are still found in the products. Presented is a Raman imaging technique for rapid, nondestructive, and spatially relevant localization of adulterants in powders. Raman spectroscopy followed by direct analyte-probed nanoextraction coupled to nanospray ionization-mass spectrometry allows rapid determination of the presence of each adulterant, leading to positive identifications such as melamine. The location and identification of these trace particles can then be extracted using a nanomanipulator. The nanomanipulation technique uses a solvent filled capillary tip which can be positioned on the particle of interest. Direct mass spectrometric analysis via nanospray of the particulate of interest eliminates time consuming chromatographic techniques prior to mass spectrometry analysis. This coupled technique combines rapid Raman spectroscopy techniques with direct mass spectrometry to confirm the presence of an adulterant. This technique was applied to an FDA supplied test sample, in which sibutramine, phenolphthalein, and melamine were confirmed to be present.

Point source attribution of ambient contamination events near unconventional oil and gas development.

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.

Chemical Sniffing Instrumentation for Security Applications.

Border control for homeland security faces major challenges worldwide due to chemical threats from national and/or international terrorism as well as organized crime. A wide range of technologies and systems with threat detection and monitoring capabilities has emerged to identify the chemical footprint associated with these illegal activities. This review paper investigates artificial sniffing technologies used as chemical sensors for point-of-use chemical analysis, especially during border security applications. This article presents an overview of (a) the existing available technologies reported in the scientific literature for threat screening, (b) commercially available, portable (hand-held and stand-off) chemical detection systems, and (c) their underlying functional and operational principles. Emphasis is given to technologies that have been developed for in-field security operations, but laboratory developed techniques are also summarized as emerging technologies. The chemical analytes of interest in this review are (a) volatile organic compounds (VOCs) associated with security applications (e.g., illegal, hazardous, and terrorist events), (b) chemical "signatures" associated with human presence, and