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True One Cell (TOC) analysis Is becoming highly critical for functional studies of cancer cells. This is partially because it is the only form of analysis that provides an avenue for studying the heterogeneity and cell-to-cell variations of individual cancer cells, thus providing unique insight into complex regulatory processes that govern TOC functions within a tumor. Additionally, true one cell techniques are playing an increasingly important role in current attempts to implement TOC metabolomic and proteomic studies, as well as emerging attempts to spatially resolve TOC information. In this review we provide a brief overview of the basis of the field and discuss its applications in TOC metabolomics and proteomics.

Silver nanoparticles (AgNPs) have become increasingly popular in the biomedical field over the last few decades due to its proven anti-bacterial 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 sub-acute inhalation exposure of AgNP (200 ppb/d over 4 hr/d exposure, for 5 d) and their livers were analysed 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-1β, 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 (CAT), and superoxide dismutase (SOD), and oxidative stress, as assessed via 8-Oxo-2’-deoxyguanosine (8-OHdG) staining. Increased oxidative stress was associated with increased monocyte/macrophage (MOMA)-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.

Two types of cobalt porphyrins, viz., meso-tetrakis(tolylporphyrinato)cobalt(II), (TTP)Co (1), and meso-tetrakis(triphenylamino porphyrinato)cobalt(II), [(TPA)4P]Co, (2) were self-assembled via metal-ligand axial coordination of phenyl imidazole functionalized fulleropyrrolidine, ImC[Formula: see text] to form a new series of donor–acceptor constructs. A 1:2 complex formation with ImC[Formula: see text] was established in the case of (TTP)Co while for [(TPA)4P]Co only a 1:1 complex was possible to positively identify. The binding constants [Formula: see text] and [Formula: see text] for step-wise addition of ImC[Formula: see text] to (TTP)Co were found to be 1.07 × 105 and 3.20 × 104 M[Formula: see text], respectively. For [(TPA)4P]Co:ImC[Formula: see text], the measured [Formula: see text] values was found to be 6.48 × 104 M[Formula: see text], slightly smaller than that observed for (TTP)Co. Although both cobalt porphyrins were non-fluorescent, they were able to quench the fluorescence of ImC[Formula: see text] indicating occurrence of excited state events in the supramolecular donor-acceptor complexes. Electrochemistry coupled with spectroelectrochemistry, revealed the formation of cobalt(III) porphyrin cation instead of a cobalt(II) porphyrin radical cation, as the main product, during oxidation of phenyl imidazole coordinated cobalt porphyrin. With the help of computational and electrochemical results, an energy level diagram was constructed to witness excited state photo-events. Competitive energy and electron transfer from excited CoP to coordinated ImC[Formula: see text], and electron transfer from Im1C[Formula: see text]* to cobalt(II) porphyrin resulting into the formation of PCo[Formula: see text]:ImC[Formula: see text] charge separated state was possible to envision from the energy diagram. Finally, using femtosecond transient absorption spectroscopy and data analysis by Glotaran, it was possible to establish sequential occurrence of energy transfer and charge separation processes. The lifetime of the final charge separated state was [Formula: see text] 2 ns. A slightly better charge stabilization was observed in the case of [(TPA)4P]Co:ImC[Formula: see text] due to the presence of electron rich, peripheral triphenylamine substituents on the cobalt porphyrin.

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.

Objectives To report a severe case of e-cigarette or vaping product use-associated lung injury with complex course requiring venovenous extracorporeal membrane oxygenation. Design Case report. Setting PICU in an academic medical center. Patients A 16-year-old girl presenting with gastrointestinal and respiratory symptoms was admitted to our PICU after having progressive respiratory failure and bilateral pulmonary ground-glass opacities on chest CT. Interventions Venovenous extracorporeal membrane oxygenation MEASUREMENTS AND MAIN RESULTS:: After extensive infectious workup was unrevealing, she reported a history of vaping e-cigarette containing either nicotine or delta-9-tetrahydrocannabinol oil prior to symptom onset. She was given a presumptive diagnosis of e-cigarette or vaping product use-associated lung injury. The PICU team in consultation with pulmonology and medical toxicology started high-dose IV methylprednisolone 1 mg/kg bid. Despite initial improvements, she continued to require positive pressure ventilation and developed pneumomediastinum with progression to tension pneumothoraces and a persistent air leak. Unable to maintain her oxygenation, she was placed on venovenous extracorporeal membrane oxygenation for a prolonged course and had a tracheostomy placement. The clinical course, severity, and range of interventions in affected patients around the country have varied widely. Respiratory symptoms have been the most severe, but the constellation of symptoms in e-cigarette or vaping product use-associated lung injury include constitutional symptoms (fevers, weight-loss) and gastrointestinal symptoms (nausea, vomiting, diarrhea). In many cases, steroid use led to rapid clinical improvements. However, other cases with severe illness, like our patient, necessitated high-dose IV steroids, intubation, and venovenous extracorporeal membrane oxygenation. The underlying etiology and pathophysiology of e-cigarette or vaping product use-associated lung injury remains unknown. The Centers for Disease Control and Prevention in conjunction with state/local health departments and the Food and Drug Administration is actively investigating the outbreak. Conclusions Clinicians need to be aware of the current outbreak of e-cigarette or vaping product use-associated lung injury and ask about vaping in patients presenting with gastrointestinal and respiratory symptoms. Treatment options are anecdotal and necessitate a multidisciplinary approach.

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.

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.

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.

This comparative study proposes an efficient technique by employing a synthetic substrate, which is commercially available, for direct, sensitive, efficient and fast analysis in Paper Spray Mass Spectrometry (PS-MS). The Teslin® substrate is a well-known synthetic paper used in the printing industry, and it is made with a single-layered, microporous polyolefin–silica matrix. Currently, filter paper is one of the most commonly used natural cellulose fiber-based substrates in PS-MS. In this study, the analytical performance of Teslin® vs. filter paper was determined by measuring different physical characteristics such as porosity, solvent elution efficiency and sensitivity of both substrates. The key result of electrostatic-spray ionization in the hydrophobic Teslin® substrate was more efficient detection and direct analysis of a smaller amount of drug samples (1 μL) with an improved signal sensitivity of 26.94-fold in comparison to filter paper. It has been demonstrated that the efficiency of reproducibility of the analyte, signal-noise ratio, and constant longer active signal (>2 min) were notably improved with the hydrophobicity of Teslin® paper by eliminating chromatographic effects. The limit of detection for drug analysis was reported to be in the lower μg mL−1 range.

Electronic cigarettes (e-cigarettes) are battery-operated devices to insufflate nicotine or other psychoactive e-liquid aerosols. Despite initial claims of e-cigarettes as a nicotine-cessation device, aggressive marketing of e-cigarettes has led to an explosion in adolescents’ and young adults’ use over the last few years. Coupled with a lack of adequate investigation and regulation of e-cigarettes, the USA is facing an outbreak of e-cigarette, or vaping, product use-associated lung injury (EVALI) starting in mid-2019. While little long-term health hazard data are available, the components and constituents of e-cigarettes may adversely impact health. Propylene glycol and glycerin are humectants (water-retaining excipients) that generate pulmonary irritants and carcinogenic carbonyl compounds (e.g., formaldehyde, acetaldehyde, and acrolein) when heated in e-cigarettes. Metals contained in heating coils and cartridge casings may leach metals such as aluminum, chromium, iron, lead, manganese, nickel, and tin. Flavoring agents are considered safe for ingestion but lack safety data for inhalational exposures. Diacetyl, a common buttery flavoring agent, has known pulmonary toxicity with inhalational exposures leading to bronchiolitis obliterans. In 2019, clusters of lung injury associated with e-cigarette use were identified in Wisconsin and Illinois. Patients with EVALI present with a constellation of respiratory, gastrointestinal, and constitutional symptoms. Radiographically, patients have bilateral ground glass opacifications. As of February 18, 2020, the Centers for Disease Control has identified 2807 hospitalized patients diagnosed with either “confirmed” or “probable” EVALI in the US. Currently, vitamin E acetate (VEA) used as a diluent in tetrahydrocannabinol vape cartridges is implicated in EVALI. VEA cuts tetrahydrocannabinol oil without changing the appearance or viscosity. When inhaled, pulmonary tissue lacks the mechanism to metabolize and absorb VEA, which may lead to its accumulation. While most EVALI patients were hospitalized, treatment remains largely supportive, and use of corticosteroids has been associated with clinical improvement. The outbreak of EVALI highlights the need for regulation of e-cigarette devices and e-liquids. Clinicians need to be aware of the health hazards of e-cigarettes and be vigilant in asking about vaping.

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.

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.

The widespread distribution and variety of fentanyl-related opioids has prompted many forensic researchers to begin exploring new techniques to carefully process and identify the many components of these seized exhibits. While these analyses typically consist of chromatographic separation, this can be a tedious and time-consuming process. To improve upon the accurate detection and structural elucidation of the components of these complex samples, a direct-infusion technique was utilized with ESI–MS on both a triple quadrupole and Orbitrap mass spectrometer to both structurally identify and propose reaction mechanisms for minor, unknown components. Results from these direct-infusion experiments suggest amine oxide formation and O-acetylation within crude reaction mixtures of both fentanyl and acetylfentanyl producing ions at m/z 395 and 353, respectively. Other previously detected components, including both byproducts and degradation products, of these samples have also been identified by their exact masses and fragmentation. Complementary fragmentation and exact mass data from these experiments can be used to accurately profile new, unknown components and help exclude potential isobaric interferences.

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.

There has been a significant demand for the development and improvement of technology used for the detection and identification of Chemical Warfare Agents (CWAs). Some of the current detection technology being used by the U.S. government includes multipass gas cell coupled Fourier Transform Infrared (FTIR) spectroscopy and Lightweight Chemical Detectors (LCD) systems. While these systems possess adequate sensitivity to detect CWAs in general, their analysis times are not considered 'rapid' nor are they able to identify the specific CWA. The U.S. Army Dugway Proving Ground's annual S/K Challenge event provides the opportunity to assess the performance and reliability of prospective detection instrumentation being developed by researchers worldwide to optimize their performance. To do so, trial testing of CWA simulants in both indoor and outdoor environments was performed, mimicking past attack scenarios. Membrane Inlet Mass Spectrometric (MIMS) technology on a portable system was successful in performing a rapid analysis along with identification of each CWA simulant utilized during the trials. The MIMS system can detect and quantify low-mass permeable compounds with parts-per-trillion limits of detection. This allows for analysis to be achieved within seconds after the initial exposure time, which is significantly faster than the FTIR and LCD systems currently used.

Investigations into anthropogenic sources of pollutants in the remote region of Puerto Williams, Chile utilized a fieldable portable mass spectrometer for on-site analysis targeting water and atmospheric air. This expedition highlights the benefits of portable instrumentation that is readily taken out into the field, in providing the community with scientific evidence of ongoing contamination. Two notable locations exhibited noticeable quantities of BTEX constituents, while remote regions remain untainted. Correlations between distance to the community and the sampling sites are indicative of sources of pollutants being anthropogenic in nature.

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 a spot diameters as low as 6 µm. Studies previously undertaken by our group have shown that the technique can provide good precision (5%) for analysing drug molecules in 150 µm diameter areas of homogenised tissue, provided an internal standard is sprayed on to the tissue prior to analysis. However, without an isotopically labelled standard, the repeatability is poor, even after normalisation to and 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 homogenised 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%.

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.

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.

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.

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.

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.

New genomic resources for jojoba reveal insights into its phylogeny and the spatial differences of lipid synthesis and storage., 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.

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.

We investigate the conditions under which electron irradiation at 2 keV of single-wall carbon nanotube (SWCNT) bundles produces an increase in the Raman D peak. We find that irradiation of SWCNTs that are preheated in situ at 600 °C for 1 h in ultrahigh vacuum before irradiation does not result in an increase in the D peak. Irradiation of SWCNTs that are preheated in vacuum and then exposed to air or gases results in an increase in the D peak, suggesting that adsorbates play a role in the increase in the D peak. Small diameter SWCNTs that are not preheated or preheated and then exposed to air show a significant increase in the D and G bands after irradiation. X-ray photoelectron spectroscopy shows no chemical shifts in the C 1s peak of SWCNTs that have been irradiated versus SWCNTs that have not been irradiated, suggesting that chemisorption of adsorbates is not responsible for the increase in the D peak.

Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) has been coupled to direct analyte-probed nanoextraction (DAPNe) through use of nanomanipulation for the analysis of ink chemistry on documents. DAPNe is first used to extract ink from the document and then deposits the sample on the MALDI plate. Through this method, cutting the document for MALDI-MS analysis is avoided. DAPNe extracts ink from documents with minimal to no visible destruction. Specific dyes and binding agents in the extracted ink are monitored with mass spectrometry. Different matrices, 1, 5-diaminonapthalene (DAN), 2, 5-dihydroxybenzoic acid (DHB), and silver nanoparticles, were tested to compare intensity enhancement of the mass spectra signals. The advantages of using MALDI-MS coupled to DAPNe are shown by characterizing Crystal Violet, Basic Yellow 2, Rhodamine B, and polyethylene glycol from red and blue pens, black pen, and a black inkjet printer cartridge.

In this work, synthetic phenethylamine drug analogues were synthesized using a shotgun method and rapidly characterized via electrospray ionization-mass spectrometry (ESI-MS) for structural confirmation, determination of partition coefficients (Log P) by a chloroform/water system, and evaluation of blood–brain barrier permeability by parallel artificial membrane permeability assay (PAMPA-BBB) to determine apparent permeability (Papp). Computational methods to validate the method and calculate theoretical Log P values and molecular lipophilic potentials (MLP) were used to supplement experimental data. These data were combined with Lipinski’s Rule of Five in a searchable ACD/Labs database for quick reference by forensic practitioners.

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

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.

Direct analyte-probed nano-extraction (DAPNe) is a method of extracting material from a microscale region of a sample and provides the opportunity for detailed mass spectrometry analysis of extracted analytes from a small area. The technique has been shown to provide enhanced sensitivity compared with bulk analysis by selectively removing analytes from their matrix and has been applied for selective analysis of single cells and even single organelles. However, the quantitative capabilities of the technique are yet to be fully evaluated. In this study, various normalisation techniques were investigated in order to improve the quantitative capabilities of the technique. Two methods of internal standard incorporation were applied to test substrates, which were designed to replicate biological sample matrices. Additionally, normalisation to the extraction spot area and matrix compounds were investigated for suitability in situations when an internal standard is not available. The variability observed can be significantly reduced by using a sprayed internal standard, and in some cases, by normalising to the extracted area.

The advent of laser ablation coupled to inductively coupled plasma-mass spectrometry has allowed for the elemental analysis of solid samples in their native state, or with little sample preparation required. Furthermore, with the addition of a cooled ablation cell spatially resolved elemental imaging of soft and semi-soft samples, specifically biological tissues, is attainable. A new single Peltier element laser ablation cell is described and a demonstration of its applicability to biological sampling is discussed to evaluate its performance. Through the analysis of three different biological tissues the device is shown to provide spatially resolved images of mapped elements while maintaining the structural integrity of the tissues during the hours long sampling times.

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.

We describe a novel technique combining precise organelle microextraction with deposition and matrix-assisted laser desorption/ionization (MALDI) for a rapid, minimally invasive mass spectrometry (MS) analysis of single organelles from living cells. A dual-positioner nanomanipulator workstation was utilized for both extraction of organelle content and precise co-deposition of analyte and matrix solution for MALDI-direct organelle mass spectrometry (DOMS) analysis. Here, the triacylglycerol (TAG) profiles of single lipid droplets from 3T3-L1 adipocytes were acquired and results validated with nanoelectrospray ionization (NSI) MS. The results demonstrate the utility of the MALDI-DOMS technique as it enabled longer mass analysis time, higher ionization efficiency, MS imaging of the co-deposited spot, and subsequent MS/MS capabilities of localized lipid content in comparison to NSI-DOMS. This method provides selective organellar resolution, which complements current biochemical analyses and prompts for subsequent subcellular studies to be performed where limited samples and analyte volume are of concern. Graphical Abstract ᅟ.

Titanium dioxide nanoparticles (TiO2 NP) are one of the most abundantly utilized nanoparticles in the world. Studies have demonstrated the ability of the anatase crystal of TiO2 NP to produce reactive oxygen species (ROS) in the presence of ultraviolet radiation (UVR), a co-exposure likely to occur in aquatic ecosystems. The goal of this study was to examine the photo-induced toxicity of anatase TiO2 NP under natural sunlight to Daphnia magna. D. magna were exposed to a range of UVR intensities and anatase TiO2 concentrations in an outdoor exposure system using the sun as the source of UVR. Different UVR intensities were achieved using UVR opaque and transparent plastics. AnataseTiO2-NP demonstrated the reciprocal relationship seen in other phototoxic compounds such as polycyclic aromatic hydrocarbons (PAHs) at higher UVR treatments. The calculated 8h LC50 of anatase TiO2 NP was 139 ppb under full intensity ambient natural sunlight, 778 ppb under 50% natural sunlight, and >500 ppm under 10% natural sunlight. Mortality was also compared between animals allowed to accumulate a body burden of anatase TiO2 for 1h and organisms whose first exposure to anatase TiO2 aqueous suspensions occurred under UVR. A significantly greater toxic effect was observed in aqueous, low body burden suspensions than that of TiO2 1h body burdens, which is dissimilar from the model presented in PAHs. Anatase TiO2 presents a unique photo-induced toxic model that is different than that of established phototoxic compounds.

Oil spills on birds and other organisms have focused primarily on direct effects of oil exposure through ingestion or direct body fouling. Little is known of indirect effects of airborne volatiles from spilled oil, especially on vulnerable developing embryos within the bird egg. Here a technique is described for exposing bird embryos in the egg to quantifiable amounts of airborne volatile toxicants from Deepwater Horizon crude oil. A novel membrane inlet mass spectrometry system was used to measure major classes of airborne oil-derived toxicants and correlate these exposures with biological endpoints. Exposure induced a reduction in platelet number and increase in osmolality of the blood of embryos of the chicken (Gallus gallus). Additionally, expression of cytochrome P4501A, a protein biomarker of oil exposure, occurred in renal, pulmonary, hepatic and vascular tissues. These data confirm that this system for generating and measuring airborne volatiles can be used for future in-depth analysis of the toxicity of volatile organic compounds in birds and potentially other terrestrial organisms.

Environmental forensics utilizes analytical scientific approaches to address the release and sources of contamination within the environment. These methods often seek to reconstruct the history of deleterious environmental events, their sources, and amounts of chemicals released into the environment. Forensic methods couple well-regarded scientific approaches within the legal framework. This due diligence provides tangible science-based results that are important in a regulatory context, including chemical identification, transport of contaminants, and determinable operational histories. Problems environmental forensics address include identifying sources of contamination, defining time frames of emission, and coupling observed conditions to potential sources of contamination.

A method for the extraction and analysis of ink samples was developed using microscopy with direct analyte probe nanoextraction coupled to nanospray ionization mass spectrometry (DAPNe-NSI-MS) for localized chemical analysis of document inks. Nanomanipulation can be effectively coupled to nanospray ionization mass spectrometry providing picomolar sensitivity, and the capability to analyze ultra-trace amounts of material and reduce the required sample volume to as low as 300 nL. This new and innovative technique does not leave destructive footprints on the surface of a document. To demonstrate the breadth of this technique, analysis of inks from various eras were tested, iron gall ink and modern inks, as well as the capability to detect the oxidative products of polyethylene glycol (PEG), a common binding agent. The experimental results showed that DAPNe-NSI-MS was able to chelate iron(II) and manganese(II) ions of iron gall ink and organic components of modern and carbon-based inks. Regardless of whether the ink composition is modern or ancient, organic or inorganic, this new instrumental approach is able to identify and characterize the ingredients by modifying the extraction solvent, illustrating the potential diversity of the DAPNe technique.

Sub-eV ion deposition via soft-landing ion mobility has been utilized for a variety of applications. It has allowed for the deposition of a dielectric material onto graphene without introducing defects into the lattice structure. This deposition technique has also been used for surface enhanced Raman studies. Deposited silver has also been used as an alternative MALDI matrix for low mass compounds and shows promise for imaging applications.

Direct inject electrospray mass spectrometry offers minimal sample preparation and a "shotgun" approach to analyzing samples. However, complex matrix effects often make direct inject an undesirable sample introduction technique, particularly for trace level analytes. Highlighted here is our solution to the pitfalls of direct inject mass spectrometry and other ambient ionization methods with a focus on trace explosives. Direct analyte-probed nanoextraction coupled to nanospray ionization mass spectrometry solves selectivity issues and reduces matrix effects while maintaining minimal sample preparation requirements. With appropriate solvent conditions, most explosive residues can be analyzed with this technique regardless of the nature of the substance (i.e., nitroaromatic, oxidizing salt, or peroxide).

The authors investigate the mechanism for etching of exfoliated graphene multilayers on SiO2 by low-energy (50 eV) electron irradiation using He plasma systems for electron sources. A mechanism for this etching has been previously proposed in which the incident electrons traverse the graphene and dissociate oxygen from the SiO2 substrate at the graphene/SiO2 interface. The dissociated oxygen reacts with carbon defects formed by the electron irradiation and thereby etches the graphene from below. They study etching using graphene flakes of various thicknesses on SiO2, low and higher resistivity Si, indium tin oxide (ITO), and silicon carbide (SiC). They find that thicker layer graphene on SiO2 does not etch less than thinner layers, contrary to the previously proposed model. They find that etching does not occur on low-resistivity Si and ITO. Etching occurs on higher resistivity Si and SiC, although much less than on SiO2. This is attributed to He ion sputtering and vacancy formation. From these observations, they propose that oxygen etches graphene from above rather than below. In addition, they propose He ions instead of incident electrons cause the defects that oxygen reacts with and etches.The authors investigate the mechanism for etching of exfoliated graphene multilayers on SiO2 by low-energy (50 eV) electron irradiation using He plasma systems for electron sources. A mechanism for this etching has been previously proposed in which the incident electrons traverse the graphene and dissociate oxygen from the SiO2 substrate at the graphene/SiO2 interface. The dissociated oxygen reacts with carbon defects formed by the electron irradiation and thereby etches the graphene from below. They study etching using graphene flakes of various thicknesses on SiO2, low and higher resistivity Si, indium tin oxide (ITO), and silicon carbide (SiC). They find that thicker layer graphene on SiO2 does not etch less than thinner layers, contrary to the previously proposed model. They find that etching does not occur on low-resistivity Si and ITO. Etching occurs on higher resistivity Si and SiC, although much less than on SiO2. This is attributed to He ion sputtering and vacancy formation. From these observatio...

The statins competitively inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase activity and consequently the synthesis of mevalonate. The use of statins is associated with insulin resistance, presumably due to the impaired differentiation and diminished glucose utilization of adipocytes. We hypothesize that mevalonate is essential to adipocyte differentiation and adipogenic gene expression. Adipo-Red assay and Oil Red O staining showed that an eight-day incubation with 0–2.5 µmol/L lovastatin dose-dependently reduced the intracellular triglyceride content of murine 3T3-F442A adipocytes. Concomitantly, lovastatin downregulated the expression of peroxisome proliferator-activated receptor γ ( Pparγ), leptin ( Lep), fatty acid binding protein 4 ( Fabp4), and adiponectin ( AdipoQ) as measured by quantitative real-time polymerase chain reaction (real-time qPCR). The expression of sterol regulatory element binding protein 1 ( Srebp-1), a transcriptional regulator of Pparγ and Lep genes, was also suppressed by lovastatin. Western-blot showed that lovastatin reduced the level of CCAAT/enhancer binding protein α (C/EBPα) while inducing a compensatory over-expression of HMG CoA reductase. The impact of lovastatin on intracellular triglyceride content and expression of the adipogenic genes was reversed by supplemental mevalonate. Mevalonate-derived metabolites have essential roles in promoting adipogenic gene expression and adipocyte differentiation.

RATIONALE While electrospray ionization is a popular technique for mass analysis, without a charged species it is ineffective. This coupled with solvent restrictions hinders the analysis of organometallic complexes. Detecting neutral species whose solubility is limited to nonconventional solvents is a problemthat can be overcome with the right charge carrier, which is described in this study. METHODS Ionic liquids were synthesized and analyzed by electrospray ionization quadrupole ion trap mass spectrometry. The neutral palladium complex was also analyzed using different imidazolium salts as the charge carrier with the same method and instrumentation. Theoretical complementswere also performed using Gaussian 09 at the density functional theory levels, using B3LYP functionals and the 6-31 g (d,p) basis set for geometry optimizations. RESULTS Low concentration imidazolium salts in methanol showed aggregation behavior of the ionic liquid, where the cation peak and [cation]n+1[anion]n peaks were observed in positive mode, while the [cation]n[anion]n+1 peaks were seen in negative mode. The unbound anion was observed in all the negative mode spectra except for the salt with the SCN anion when in THF. Solutions of PdCl2(PPh3)2 and a small amount of ionic liquid in THF showed the palladium complex adducted with the imidazolium cation for each of the ionic liquids studied. CONCLUSIONS A charge carrier for a neutral organometallic complex was found in imidazolium salts, where the cation was observed as the ionizing agent. Differing ion intensities of the complex-adduct peak resulted from the anions ability to dissociate from the cation. Copyright © 2013 John Wiley & Sons, Ltd.

Here, we present a method of extracting drug residues from fingerprints via Direct Analyte-Probed Nanoextraction coupled to nanospray ionization-mass spectrometry (DAPNe-NSI-MS). This instrumental technique provides higher selectivity and lower detection limits over current methods, greatly reducing sample preparation, and does not compromise the integrity of latent fingerprints. This coupled to Raman microscopy is an advantageous supplement for location and identification of trace particles. DAPNe uses a nanomanipulator for extraction and differing microscopies for localization of chemicals of interest. A capillary tip with solvent of choice is placed in a nanopositioner. The surface to be analyzed is placed under a microscope, and a particle of interest is located. Using a pressure injector, the solvent is injected onto the surface where it dissolves the analyte, and then extracted back into the capillary tip. The solution is then directly analyzed via NSI-MS. Analyses of caffeine, cocaine, crystal methamphetamine, and ecstasy have been performed successfully.

We study oxidative pit formation in pristine, hydrogenated, and dehydrogenated monolayer graphene (MLG), bilayer graphene (BLG) and trilayer graphene (TLG). Graphene samples are produced by mechanical exfoliation of highly oriented pyrolytic graphite (HOPG) onto SiO 2 substrates. Etching is carried out by exposing samples to O 2 gas at 450–700 °C. Using atomic force microscopy, we observe that pre-heating pristine MLG in vacuum at 590 °C increases the onset temperature for pit formation to values comparable to those in HOPG. We attribute this decrease in reactivity to an increase in adhesion between the MLG and substrate. In hydrogenated MLG and BLG, we observe a significant decrease in the onset temperature for pit formation. Dehydrogenation of these materials results in a decrease in the density of pits. We attribute the decrease in onset temperature to H-related defects in their sp 3 -bonded structure. In contrast, hydrogenated TLG and thicker-layer samples show no significant change in pit formation. We propose that this is because they are not transformed into an sp 3 -bonded structure by hydrogenation.

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.

Breast cancer develops in an adipose rich environment of normal adipocytes that are known to aid in tumor progression through an unknown method of lipid transfer from normal cells to tumor cells. Much research is built around lipid analysis of breast tumor and adjacent normal tissues to identify variations in the lipidome to gain an understanding of the role lipids play in progressing cancer. Ideally, single-cell analysis methods coupled to mass spectrometry that retain spatial information are best suited for this endeavor. However, many single-cell analysis methods are not capable of subcellular analysis of intact lipids while maintaining spatial information. One-Cell analysis is a true single-cell technique with the precision to extract single organelles from intact tissues while not interfering or disrupting adjacent cells. This method is used to extract and analyze single organelles from individual cells using nanomanipulation coupled to nanoelectrospray ionization mass spectrometry. Presented here is a demonstration of the analysis of single lipid bodies from two different sets of breast tumor and normal adjacent tissues to elucidate the fatty acid composition of triglycerides using One-Cell analysis coupled to tandem mass spectrometry. As a result, thirteen fatty acid species unique to the tumor tissues were identified, five in one set of tissues and eight in the other set.

The method of residue extraction through electrostatic lifting provides a distinctive mode of performing ultra-trace analysis. These lifts provide a medium for analyte extraction via nanomanipulation-coupled to nanospray ionization–mass spectrometry (NSI–MS). This method of extraction can be coupled to Raman spectroscopy for supplemental verification of analytes using surface enhanced Raman scattering (SERS). The gold surface used for SERS provides an enhanced effect on peak signal intensity allowing ultra-trace amounts to be detected more effectively. The aim of this research is to utilize gold-coated films with electrostatic lifting in order to collect latent materials and analyze chemicals of interest contained in them via SERS.