On-tissue chemical derivatization enables spatiotemporal heterogeneity visualization of oxylipins in esophageal cancer xenograft via ambient mass spectrometry imaging

On-tissue chemical derivatization(OTCD)effectively enhances ionization efficiency of low abundant and poorly ionized functional molecules to improve detection sensitivity and coverage of mass spectrometry imaging(MSI).Combination OTCD and MSI provides a novel strategy for visualizing previously undisclosed metabolic heterogeneity in tumor.Herein,we present a method to visualize heterogeneous metabolism of oxylipins within tumor by coupling OTCD with airflow-assisted desorption electrospray ionization(AFADESI)-MSI.Taking Girard’s P as a derivatization reagent,easily ionized hydrazide and quaternary amine groups were introduced into the structure of carbonyl metabolites via condensation reaction.Oxylipins,including 127 fatty aldehydes(FALs)and 71 oxo fatty acids(FAs),were detected and imaged in esophageal cancer xenograft with AFADESI-MSI after OTCD.Then t-distributed stochastic neighbor embedding and random forest were exploited to precisely locate the distribution of oxylipins in heterogeneous tumor tissue.With this method,we surprisingly found almost all FALs and oxo FAs significantly accumulated in the core region of tumor,and exhibited a gradual increase trend in tumor over time.These results reveal spatiotemporal heterogeneity of oxylipins in tumor progression,highlighting the value of OTCD combined with MSI to gain deeper insights into understanding tumor metabolism.

Porous covalent organic frameworks-improved solid phase microextraction ambient mass spectrometry for ultrasensitive analysis of tetrabromobisphenol-A analogs

Owing to frequent environmental monitoring of tetrabromobisphenol-A(TBBPA)analogs and their potential ecotoxicological effects on organisms,analysis of trace levels of TBBPA analogs with more non-polar and less water-soluble characteristics is of great significance for studying their environmental behaviors and toxic effects.Herein,a fast and sensitive technique is developed for directly detecting aqueous TBBPA analogs,including TBBPA mono(allyl ether)(TBBPA-MAE),TBBPA mono(2,3-dibromopropyl ether)(TBBPAMDBPE),TBBPA mono(2-hydroxyethyl ether)(TBBPA-MHEE)and TBBPA mono(glycidyl ether)(TBBPAMGE),by combining solid phase microextraction(SPME)based on porous covalent organic frameworks(Porous-COFs)with constant flow desorption ionization-mass spectrometry(CFDI-MS).As chromatographic separation is replaced by constant flow desorption,each sample can be analyzed within 7 min.The hierarchical porous structures(microporous,mesoporous and macroporous)of COFs lead to the enhanced mass transfer and the easier accessibility of active sites to TBBPA analogs,so that the extraction efficiency is 2.3-3.6 times higher than pure microporous COFs,and far superior to commercial coatings.The detection limit and quantification limit of this method are 0.1-1 and 0.4-3.2 ng/L,respectively.Ultratrace levels of TBBPA analogs from 5.0 ng/L to 66 ng/L have been successfully detected in river and sea water samples,showing great potential for subsequent studies of their environmental behaviors and toxicological effects.

Analyzing Brazilian Driver’s License Authenticity by Easy Ambient Sonic-Spray Ionization Mass Spectrometry

Fast and unequivocal methods of questioned document analysis are essential in forensic science. Here, a desorption/ionization technique, EASI-MS, was assessed for its ability to investigate questioned driver’s licenses (DL). Two suspects DL, displaying the same personal data in the proper fields (name and ID numbers), but with different individual photos, showing similar impressions on microscopic analysis, and authentic standards documents specimens were used as test cases. Profiles from authentic DL surface were dominated by a set of few minor ions, mainly from the plasticizers bis(2-ethylhexyl)phthalate and dibutylphthalate. The seized suspect counterfeit DL on points from personal data and photo were, however, dominated by abundant diagnostic ions of m/z 463, 507, 551, 595, 639, 683, which confirmed counterfeiting. Surfynol® and Nonoxynol-9®, which are common constituents of inkjet printing, were detected in the counterfeiting areas by high-accuracy EASI(+)-FT-ICR MS. The EASI-MS technique is shown therefore to offer an attractive tool for forensic investigation of questioned documents.

In Situ Analysis of Tobacco Leaves Based on Microwave Plasma Torch Desorption Ionization Mass Spectrometry

Tobacco is an important economic crop worldwide.Tobacco leaves contain a large number of natural products.Therefore,the analysis of tobacco composition is crucial for the control of tobacco safety and quality assessment.Microwave plasma torch desorption ionization mass spectrometry(MPT-MS) is an emerging ambient mass spectrometry(AMS) technique that can be used for rapid real-time analysis of s amples without pretreatment.Our work focuses on the chemical composition analysis of tobacco using MPT-MS,and 14 compounds were detected in green flue-cured tobacco leaves,while 30 compounds were detected in cured flue-cured tobacco leaves,which confirms that curing can enhance the flavor of cigarettes.Furthermore,we successfully in situ identified characteristic fragment ions of α/β-CBD(α/β-cembranoids),an important aroma compound in tobacco by MPT-MS.The results demonstrate the capability of MPT-MS for in situ analysis of tobacco components and its potential for evaluating tobacco quality.

Tip-assisted ambient electric arc ionization mass spectrometry for rapid detection of trace organophosphorus pesticides in strawberry

In this study,an ambient mass spectrometry(AMS)based method was developed for rapid detection of organophosphorus pesticides in strawberry.This method combines an electric arc and a microsyringe tip to realize tip-assisted ambient electric arc ionization(TAAEAI).A high-voltage electric arc can be applied to the microsyringe tip to generate an electric field,which results in corona discharge at the microsyringe tip.The juiced strawberry sample loaded on the tip could be directly ionized with TAAEAI and then analyzed by a mass spectrometer.TAAEAI-MS was successfully applied to analyze 6 organophosphorus pesticides in three strawberry samples.Malathion and profenofos were detected from the investigated strawberry samples.This method could quantitatively determine the contents of organophosphorus pesticides in strawberry with high reproducibility,high precision,and high sensitivity.Sample matrices did not interfere with the pesticide analysis.The recoveries of organophosphorus pesticides spiked in strawberry samples varied between 82.6%and 116%with relative standard deviations(RSDs)less than 9.2%.The limits of detection(LODs)varied between 0.0124µg/g and 0.0245µg/g,while the limits of quantification(LOQs)varied between 0.0413µg/g and 0.0817µg/g.The coefficients of determination(R2)of the method were determined to be>0.995.The method established here may have potential application in the detection of organophosphorus pesticides in vegetables and fruits.

Accelerated plasma degradation of organic pollutants in milliseconds and examinations by mass spectrometry

The rapid degradation of organic pollutants,process monitoring and online controlling to obtain advanced products and decreased by-products are great and challenging tasks in environmental treatments.Herein,an accelerated plasma degradation in milliseconds was achieved by combining electrospray-based acceleration and plasma-based degradation.Taking the degradation of chloroaniline as an example,97%of the degradation can be achieved in milliseconds.The velocity distribution of droplets was determined to be 40-50 m/s after being degraded for 0.30 ms,which exhibited different degradation behaviors in different milliseconds.Simultaneously,by virtue of the real-time and on-line detection ability of ambient mass spectrometry,intermediates,by-products and advanced products were monitored.Therefore,degradation mechanisms for different degradation times were proposed,which would provide theoretical guidance on obtaining efficient and green degradation.The fabrication,examining and understanding of accelerated plasma degradation not only enlarged application of accelerated reactions,but also promoted green and efficient degradation for environmental treatments.

New Strategy for Further Improving the Detection Sensitivity of Direct Analysis in Real Time-Mass Spectrometry

Ambient mass spectrometry facilitates surface detection under ambient conditions and has quickly found its applications in various areas.However,the sensitivity of AMS methods is usually not as good as that of encapsulated ion sources due to less efficient ion transmission.In this work,a briefly machined external ion funnel(threepole electrostatic lens)was adopted and installed between direct analysis in real time and the mass spectrometer inlet to increase detection sensitivity.Software investigation with SIMION version 8.0 was employed to calculate electric fields and to simulate the trajectories of charged particles in the electric field.Both the geometrical parameters of the ion funnel and the electric parameters were studied to obtain the optimal ion focusing results,which demonstrated the ion funnel equipment would greatly improve the ion transmission efficiency.The equipment showed good prospect in direct analysis in real time-mass spectrometry analysis in the future.

Spatiotemporally resolved metabolomics and isotope tracing reveal CNS drug targets

Deconvolution of potential drug targets of the central nervous system(CNS)is particularly challenging because of the complicated structure and function of the brain.Here,a spatiotemporally resolved metabolomics and isotope tracing strategy was proposed and demonstrated to be powerful for deconvoluting and localizing potential targets of CNS drugs by using ambient mass spectrometry imaging.This strategy can map various substances including exogenous drugs,isotopically labeled metabolites,and various types of endogenous metabolites in the brain tissue sections to illustrate their microregional distribution pattern in the brain and locate drug action-related metabolic nodes and pathways.The strategy revealed that the sedative-hypnotic drug candidate YZG-331 was prominently distributed in the pineal gland and entered the thalamus and hypothalamus in relatively small amounts,and can increase glutamate decarboxylase activity to elevateγ-aminobutyric acid(GABA)levels in the hypothalamus,agonize organic cation transporter 3 to release extracellular histamine into peripheral circulation.These findings emphasize the promising capability of spatiotemporally resolved metabolomics and isotope tracing to help elucidate the multiple targets and the mechanisms of action of CNS drugs.

DART-MS:A New Research Tool for Herbal Medicine Analysis

Direct analysis in real time(DART) possesses the merits of analyzing sample in its native status with minimal or even no sample pretreatment.In this review, we summarized the recent applications of DART in the field of herbal medicine analysis such as compound detection, species identification, metabolites profiling and initial quantification. DART with the characters of hyper-rapid, easy-hyphenated offers a new research tool for herbal medicines to complete the experimental process in a very simple but still reliable way. It is anticipated that more wide and deep applications of DART in herbal medicine analysis, as rapid quantification, high-throughput active compounds screening, rapid species identification, and fast illegal additives screening will be promising and foreseeable in the near future.