Background Acute poisoning requires the swift and accurate identification of toxicants to enable timely and effective medical interventions. Conventional specimen transportation by automobile can often be delayed due to urban traffic, geographic barriers, and unpredictable road conditions, which can postpone critical toxicant analysis. The exploration of advanced technology such as the unmanned aircraft system (UAS) and ambient ionization mass spectrometry (AIMS) addresses these challenges by expediting sample delivery and enabling rapid detection of toxic substances with minimal sample preparation. In emergency scenarios, integrating UAS and AIMS can significantly accelerate the provision of life-saving analytical data. Results This study compared and investigated the efficiency of specimen transportation between a conventional automobile and a UAS and toxicant identification using AIMS for emergency care applications. An acute pesticide poisoning scenario was simulated, which involved collecting discharged biological fluids and leftover pesticide-contaminated food on scene, transporting specimens from the poisoning site to the laboratory, and analyzing samples using thermal desorption electrospray ionization tandem mass spectrometry (TD-ESI/MS/MS) to identify pesticides. Data on transportation times, geographical barriers, and road conditions were recorded and compared. Quantitative analysis of pesticides using TD-ESI/MS/MS showed a linear response for fenthion between 5 ppb and 2 ppm (R2 = 0.9905), and the method demonstrated good reproducibility with a relative standard deviation of 12.7% over ten consecutive analyses of a 1 ppm standard solution. Significance and Novelty This study underscores the transformative potential of the use of UAS technology in expediting specimen transportation and TD-ESI/MS/MS in simplifying and accelerating toxicant identification for emergency medicine applications. These findings can support the further integration of these innovative technologies to optimize patient care in acute poisoning cases.

In this study, we integrated an unmanned aircraft system for efficient sample delivery and an ambient ionization mass spectrometric technique for the rapid and reliable assessment of seafood freshness in an emergency care scenario involving food poisoning. A drone was used to deliver specimens from a seafood restaurant directly across a Kaohsiung port to a nearby mass spectrometry laboratory, overcoming geographic constraints and shortening delivery time by about 30 minutes compared to conventional automobile-based transport through an undersea tunnel. The efficiency of sample transportation was evaluated based on recorded data including travel duration, topographical obstructions, and road conditions. Upon arrival, samples underwent immediate analysis using probe sampling combined with TD-ESI/MS/MS, which enabled the rapid detection of histamine, a spoilage marker and biogenic amine, without the need for complex sample pretreatment. This research highlights the transformative potential of rapid sample delivery (through advanced aerial systems) and screening technology (through ambient ionization tandem mass spectrometry) to improve the efficiency of emergency responses and support public health management in remote regions with limited health and social infrastructure. Furthermore, TD-ESI/MS/MS supports greener analytical workflows by enabling probe-based micro-sampling (≪2 μL) and rapid sample analysis (≤1 min), thereby reducing the use of reagents, solvents, and consumables, and decreasing the production of analytical waste compared to conventional preparation-intensive methods.

Background:Psoriasis is a chronic inflammatory disease with an unclear etiology that affects skin, nails, and joints and often accompanies comorbidities. Recent studies indicate that alterations in metabolites within psoriatic lesions might be linked to inflammation. Studying bioactive lipid mediators or metabolites in skin inflammation and immunity might provide new potential biomarkers and therapeutic prediction factors. Methods:Lipids and peptides in the scale extracts from psoriasis patients and healthy controls were characterized by thermal desorption-electrospray ionizationmass spectrometry and matrix-assisted laser desorption/ionization time-of-flightmass spectrometry, respectively. Principal component analysis (PCA) was then applied to these data to identify potential differences between psoriasis patients and healthy controls. Results:Psoriatic plaques show reduced wax esters and triglycerides and a predominant increase in human neutrophil defensins (HNPs), compared to non-lesional sites of psoriatic patients and healthy control. Additionally, when medical treatments were administered to psoriasis patients, levels of HNPs were significantly reduced, suggesting that they may serve as potential biomarkers to evaluate therapeutic efficacy for psoriasis. Conclusion:Two mass spectrometric techniques were used to rapidly and non-invasively identify and monitor potential biomarkers between psoriasis patients and healthy controls. However, PCA results only showed slight differences, and we intend to broaden the sample base in the future to increase the statistical power of the investigation.

Background:Typing Mycobacterium tuberculosis (MTB) isolates is important for identifying clusters and guiding infection control measures. Although whole-genome sequencing (WGS) and 24-loci mycobacterial interspersed repetitive units-variable-number tandem repeat (MIRU-VNTR) are widely used for molecular typing, they may not capture phenotypic or metabolic variation. Alternative approaches, such as mass spectrometric-based profiling, could provide complementary insights. Methods:A total of 247 clinical MTB isolates were analyzed by thermal desorption-electrospray ionization mass spectrometry (TD-ESI/MS). The resulting mass spectral profiles were evaluated using principal component analysis (PCA) and hierarchical clustering analysis (HCA). Results were compared with lineage classifications based on WGS and MIRU-VNTR to assess concordance. Results:While WGS and MIRU-VNTR were highly concordant for lineage classification (98.8%; 244/247), TD-ESI/MS revealed diverse spectral profiles that did not align consistently with genetic lineages. However, HCA showed isolate-level clustering, including among genetically similar strains, suggesting that TD-ESI/MS may detect metabolic or lipidomic differences not captured by genome-based methods. Conclusion:Although TD-ESI/MS does not generate similar results from MTB molecular typing, it shows potential for identifying specific spectral signatures. The technique may be useful in future investigations into phenotypic diversity and other clinically relevant features not captured by genotyping alone.

Food safety is a critical global issue, with food oil fraud being a particularly common occurrence over the past decade. Although gas chromatography/mass spectrometry (GC/MS) is commonly used to determine chemical components in edible oils, sample preparation is often labor-intensive and time-consuming, highlighting the need for an efficient platform to distinguish oil types for food safety. In this study, thermal desorption-electrospray ionization/mass spectrometry (TD-ESI/MS), an ambient ionization mass spectrometry (AIMS), has been employed in the analysis of various chemical compounds with minimal sample preparation. TD-ESI/MS coupled with probe sampling and principal component analysis (PCA) were used to rapidly analyze oil components and classify different oils in the triglyceride mass range (m/z > 800). Eighty-four oil samples were grouped into categories including edible/non-edible, saturated/unsaturated/highly unsaturated, and edible/gutter oil, demonstrating the potential of this analytical platform for food safety applications.

Background A regular face mask is comprised of three layers for resisting moisture, filtration, and absorbing oral fluid, respectively. Since the polymers with different polarities are used to make the layers, a face mask can be used as a sampling tool to retain polar or non-polar chemical and biochemical substances in the exhaled breath. In this study, thermal desorption-electrospray ionization tandem mass spectrometry (TD-ESI/MS/MS), an ambient ionization mass spectrometric technique, was used to detect trace acetaminophen that were exhaled and retained on the surface of different layers in a face mask. Results With probe sampling combined with TD-ESI/MS/MS, the acetaminophen ion signal can be detected at the mouth/nostril region of the face mask after taking the acetaminophen tablet. The experimental results were similar to previous studies for the detection of acetaminophen in blood over time using LC/MS/MS. In addition, the intensities of acetaminophen on different layers of the face mask could reveal the differing distributions of exhaled acetaminophen on each layer. To explore the distribution of acetaminophen on the face mask surface, multiple probes were used to collect samples from different locations of the face mask for analysis. The molecular mapping of acetaminophen on the face mask was rendered by scaling the analyte ion signal intensity based on a temperature color gradient. The cartography showed a higher acetaminophen ion signal distribution on the mouth and nostril regions than in other areas of the face mask. Significance Owing to the advantages of a simple, sensitive, and non-invasive sampling approach, drug monitoring could be potentially performed to provide useful information for anti-drug of precision medicine in the future.

Background A mysterious skin rash (papular lesions) outbreak broke out for unknown reasons in Taiwan’s Pescadores Islands in mid-autumn 2021, causing much anxiety in the population already nervous about the ongoing COVID-19 epidemic. Objectives We conducted a field survey for possible culprit agents. Methods Skin samples were taken with rapid-glue adhesives from the affected skin. Electron microscopy from the skin samples as well as caterpillar seta was performed. Additional neurotransmitter analysis by mass spectrometry (MS) was conducted on the skin samples. Results A field survey found a large increase in caterpillars, Euproctis taiwana, in September 2021, the warmest September in recent years. Electron microscopy performed on superficial skin samples (3–6 cells thick) of affected and healthy skin (n = 5 and 3, respectively) and caterpillar setae revealed ultrastructural similarities between setae spurs (0.15–0.2 μm) and tiny pits (0.2 μm) on the affected skin as well as similar vegetative debris (0.75 μm) on both setae and affected skin. MS showed large increases in tyrosine, serine, and histamine, known mediators of arthropod insult. Conclusion The co-occurrence of E. taiwana population growth, excessive warming, and strong monsoon winds may lead to this unusual autumn outbreak in late September. The lifting of COVID-19-related travel restrictions against earlier that month probably exacerbated it.

In Asia, some herbal preparations have been found to be adulterated with undeclared synthetic medicines to increase their therapeutic efficiency. Many of these adulterants were found to be toxic when overdosed and have been documented to bring about severe, even life-threatening acute poisoning events. The objective of this study is to develop a rapid and sensitive ambient ionization mass spectrometric platform to characterize the undeclared toxic adulterated ingredients in herbal preparations. Several common adulterants were spiked into different herbal preparations and human sera to simulate the clinical conditions of acute poisoning. They were then sampled with a metallic probe and analyzed by the thermal desorption-electrospray ionization mass spectrometry. The experimental parameters including sensitivity, specificity, accuracy, and turnaround time were prudently optimized in this study. Since tedious and time-consuming pretreatment of the sample is unnecessary, the toxic adulterants could be characterized within 60 s. The results can help emergency physicians to make clinical judgments and prescribe appropriate antidotes or supportive treatment in a time-sensitive manner.

Mushroom poisoning occurs frequently after the ingestion of toxic wild mushrooms misidentified as edible species. The goal of this study is to develop a mass spectrometric platform to bypass the need for morphological recognition of poisonous mushrooms by experts and rapidly identify the toxins in the mushrooms for emergency care. Trace mushroom toxins were collected by penetrating and removing the mushrooms surface for 3 mm with a direct electrospray probe (DEP). The analytes on the DEP were then dissolved in the solution (70% isopropanol containing 0.1% acetic acid) flowing out of a solvent reservoir on the DEP. Electrospray ionization was induced from the sample solution as a high electric field was generated between the DEP and MS inlet. The obtaining mass spectrometric results were further analyzed with principal component analysis (PCA) to classify mushroom toxins. The mass spectrometric platform for detecting mushroom toxins was assessed for its sensitivity, precision, and efficiency by determining its limit-of-detection (LOD), repeatability, and turnaround time, respectively. As a result, the LODs of the mushroom toxins in pure methanol and spiked in human vomitus by DEP/MS were within 0.001-0.5 ng/mu L and 0.01-1 ng/mu L, respectively. Linear responses of the mushroom toxins in pure methanol with concentrations between 0.01 and 5 ng/mu L (R-2 between 0.9922 and 0.998) were obtained. The repeatability of the approach (n = 10) was shown in the low relative standard deviation value (<15%) from ten repeat analysis of mushroom toxins standard solution. The corresponding toxic compounds were identified through matching of the obtained mass spectrometric data with those provided by its companion database library of mushroom toxins. Since no time-consuming pretreatment of the samples is required, identification of mushroom toxins with DEP/MS was complete within 1 min. This will be helpful for the emergency physicians to make correct clinical judgment and prescribe appropriate medical treatment in a timely manner.

In the emergency department, it is important to rapidly identify the toxic substances that have led to acute poisoning because different toxicants or toxins cause poisoning through different mechanisms, requiring disparate therapeutic strategies and precautions against contraindicating actions, and diverse directions of clinical course monitoring and prediction of prognosis. Ambient ionization mass spectrometry, a state-of-the-art technology, has been proved to be a fast, accurate, and user-friendly tool for rapidly identifying toxicants like residual pesticides on fruits and vegetables. In view of this, developing an analytical platform that explores the application of such a cutting-edge technology in a novel direction has been initiated a research program, namely, the rapid identification of toxic substances which might have caused acute poisoning in patients who visit the emergency department and requires an accurate diagnosis for correct clinical decision-making to bring about corresponding data-guided management. This review includes (i) a narrative account of the breakthrough in emergency toxicology brought about by the advent of ambient ionization mass spectrometry and (ii) a thorough discussion about the clinical implications and technical limitations of such a promising innovation for promoting toxicological tests from tier two-level to tier one level.

Ambient ionization mass spectrometry (AIMS) is both labor and time saving and has been proven to be useful for the rapid delineation of trace organic and biological compounds with minimal sample pretreatment. Herein, an analytical platform of probe sampling combined with a thermal desorption–electrospray ionization/mass spectrometry (TD-ESI/MS) and multivariate statistical analysis was developed to rapidly differentiate bacterial species based on the differences in their lipid profiles. For comparison, protein fingerprinting was also performed with matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) to distinguish these bacterial species. Ten bacterial species, including five Gram-negative and five Gram-positive bacteria, were cultured, and the lipids in the colonies were characterized with TD-ESI/MS. As sample pretreatment was unnecessary, the analysis of the lipids in a bacterial colony growing on a Petri dish was completed within 1 min. The TD-ESI/MS results were further performed by principal component analysis (PCA) and hierarchical cluster analysis (HCA) to assist the classification of the bacteria, and a low relative standard deviation (5.2%) of the total ion current was obtained from repeated analyses of the lipids in a single bacterial colony. The PCA and HCA results indicated that different bacterial species were successfully distinguished by the differences in their lipid profiles as validated by the differences in their protein profiles recorded from the MALDI-TOF analysis. In addition, real-time monitoring of the changes in the specific lipids of a colony with growth time was also achieved with probe sampling and TD-ESI/MS. The developed analytical platform is promising as a useful diagnostic tool by which to rapidly distinguish bacterial species in clinical practice.

Objectives:Isobaric tags for relative and absolute quantitation (iTRAQ) is a proteomic investigation that could be utilized for rapid identification and quantification of proteins, which we would use to identify differentially expressed proteins in treatment responsive patients with major depressive disorder (MDD).Methods:Six treatment responsive patients of MDD were recruited, and their peripheral blood mononuclear cell (PBMC) were collected before and after 4 weeks of paroxetine treatment. iTRAQ and Mascot search engine were used to detect differentially expressed proteins, which were then validated by Western blot.Results:Two thousand one hundred and fifty three proteins were screened, and seven proteins showed differences of more than two-fold and 62 proteins with a differences of less than two-fold. Six proteins with commercially available antibodies were identified, and were validated by Western blot in 10 paroxetine responsive MDD patients. Putative hydroxypyruvate isomerase (HYI), eukaryotic translation initiation factor 4H (eIF4H), and RNA binding motif 8A (RBM8A) had statistically significant differences before and after treatment in the validation. Data are available via ProteomeXchange with identifier PXD028947.Conclusions:By using iTRAQ and Western blot, we were able to identify HYI, eIF4H, and RAM8a to be the potential predictors of paroxetine treatment response in patients with MDD. This finding could help establish future individualized medicine.

We aim to develop an efficient and non-invasive strategy for monitoring of drugs and their metabolites via human skin. Probe sampling was combined with thermal desorption-electrospray ionization tandem mass spectrometry (TD-ESI/MS/MS) to characterize trace terbinafine, which was secreted on patient's skin after ingesting terbinafine tablets. The terbinafine ion signals were directly detected in the samples collected from different skin regions and the signals were monitored for 8 weeks. The detection and location of terbinafine via the skin suggest that the methods are useful in rapidly and noninvasively collecting the molecular information of the ingested drug on skin for pharmacokinetic studies.

In the emergency department, it is important to rapidly identify the toxic substances that have led to acute poisoning because different toxicants or toxins cause poisoning through different mechanisms, requiring disparate therapeutic strategies and precautions against contraindicating actions, and diverse directions of clinical course monitoring and prediction of prognosis. Ambient ionization mass spectrometry, a state-of-the-art technology, has been proved to be a fast, accurate, and user-friendly tool for rapidly identifying toxicants like residual pesticides on fruits and vegetables. In view of this, developing an analytical platform that explores the application of such a cutting-edge technology in a novel direction has been initiated a research program, namely, the rapid identification of toxic substances which might have caused acute poisoning in patients who visit the emergency department and requires an accurate diagnosis for correct clinical decision-making to bring about corresponding data-guided management. This review includes (i) a narrative account of the breakthrough in emergency toxicology brought about by the advent of ambient ionization mass spectrometry and (ii) a thorough discussion about the clinical implications and technical limitations of such a promising innovation for promoting toxicological tests from tier two-level to tier one level.

Despite the fact that carbamates and organophosphates cause acute poisoning via different mechanisms and require disparate management, they are indistinguishable by current clinical assays. Herein, direct immersion solid-phase microextraction (DI-SPME) plus thermal desorption-electrospray ionization tandem mass spectrometry (TD-ESI/MS/MS) was developed to discern them. Both pesticides spiked in human serum were extracted by SPME and analyzed by TD-ESI/MS/MS. This is a promising emergency care platform as rapid analyses could be done in tiny sample volumes with satisfactory recovery (89.46%–116.32%), precision (covariance < 20%), sensitivity (LOD < 0.1 µg/mL), turnaround time (< 5 minutes), and linearity (R2 = 0.9827–0.9992) within 0.1–100 µg/mL.

Rapid identification of the offending toxicants remains the most important part of the emergency care for acute poisoning. Nonetheless, most contemporary methods of laboratory confirmation are not timely enough and/or too technically-demanding to attain this goal. For more than half a decade, two ambient ionization mass spectrometric platforms, namely, (a) thermal desorption-electrospray ionization-mass spectrometry (TD-ESI-MS), and (b) Electrospray-assisted laser desorption ionization-mass spectrometry (ELDI-MS) have been applied to rapidly provide qualitative and semi-quantitative analyses of various toxicants and toxins found in different types of clinical specimen collected under different scenarios of emergency care. The ultimate goal of these studies is to meet the prerequisite that the end user of an ambient ionization mass spectrometry (AIMS) could eventually be a nurse or an emergency physician rather than an analytical chemist. Therefore, the design of the analytical system should be capable of taking biofluids automatically with minimal, if not without, pretreatment and generating analytical reports understandable to the end users, instead of mass spectra or chromatograms. In this article, a comprehensive account of (i) the potential clinical applications of two ambient ionization mass spectrometric platforms in the emergency care for acute poisoning and (ii) the challenges confronted by these cutting-edge technologies is unveiled.

Matrix-assisted laser desorption ionization/time-of-flight (MALDI-TOF) mass spectrometry is a sensitive analytical tool for characterizing various biomolecules in biofluids. In this study, MALDI-TOF was used to characterize potential plasma biomarkers for distinguishing patients with major depressive disorder (MDD) from patients with schizophrenia and healthy controls. To avoid interference from albumin-the predominant protein in plasma-the plasma samples were pretreated using acid hydrolysis. The results obtained by MALDI-TOF were also validated by electrospray ionization-quadrupole time-of-flight (ESI-QTOF) mass spectrometry. The analytical results were further treated with principal component analysis (PCA), hierarchical clustering analysis (HCA), and receiver operating characteristic (ROC) curve analysis. The statistical analyses showed that MDD patients could be distinguished from schizophrenia patients and healthy controls by the lack of apolipoprotein C1 (Apo C1), which, in fact, was detected in healthy controls and schizophrenia patients. This protein is suggested to be a potential plasma biomarker for distinguishing MDD patients from healthy controls and schizophrenia patients. Since sample preparation for MALDI-TOF is very simple, high-throughput plasma apolipoprotein analysis for clinical purposes is feasible.

Objective: Schizophrenia is a mental disorder characterized by reduced social engagement, abnormal emotional expression, and a lack of motivation. Isobaric tags for relative and absolute quantitation (iTRAQ) are a novel proteomic technique. In this study, we intended to identify potential biomarkers for predicting clozapine treatment response using iTRAQ. Methods: We identified patients with schizophrenia that responded to a four-week treatment with clozapine. Patient's peripheral blood mononuclear cells (PBMC) were collected before and after treatment. iTRAQ-based proteomics analysis was done to identify differentially expressed proteins in PBMC before and after treatment. STRING analysis map was built, and a target protein was selected. Western blot validation was then done. Results: In 10 identified clozapine treatment-responsive patients, we screened 2,735 proteins. Nine downregulated proteins and 11 upregulated proteins were differentially expressed by 1.5-fold after clozapine treatment. STRING network analysis revealed a series of apolipoproteins, and only apolipoprotein A4 (APOA-IV) was selected for validation. Western blot validations showed that protein levels of APOA-IV were significantly most downregulated in the patient after clozapine treatment (p = 0.05). Conclusion: In this study, we integrated clinical observation data, bioinformational protein interaction analysis, and iTRAQ labeling to study proteomics in patients with schizophrenia successfully treated with clozapine. We suggest that APOA-IV protein can be a biomarker for predicting clozapine treatment response in patients with schizophrenia. But these results in this study need a larger sample size to be validated.

Squalene (SQ), a highly unsaturated sebaceous lipid, plays an important role in protecting human skin. To better understand the role of SQ in clinical medicine, an efficient analytical approach is needed to comprehensively study the distribution of SQ on different parts of the skin. In this study, sebaceous lipids were collected from different epidermal areas of a volunteer with sampling probes. Thermal desorption-electrospray ionization/mass spectrometry (TD-ESI/MS) was then used to characterize the lipid species on the probes, and each TD-ESI/MS analysis was completed within a few seconds without any sample pretreatment. The molecular mapping of epidermal squalene on whole-body skin was rendered by scaling the peak area of the extracted ion current (EIC) of SQ based on a temperature color gradient, where colors were assigned to the 1357 sampling locations on a 3D map of the volunteer. The image showed a higher SQ distribution on the face than any other area of the body, indicating the role of SQ in protecting facial skin. The results were in agreement with previous studies using SQ as a marker to explore sebaceous activity. The novelty and significance of this work are concluded as two points: (1) direct and rapid detection of all major classes of sebaceous lipids, including the unsaturated hydrocarbons (SQ) and nonpolar lipids (e.g., cholesterol). The results are unique compared to other conventional and ambient ionization mass spectrometry methods and (2) this is the first study to analyze SQ distribution on the whole-body skin by a high-throughput approach.