Journal of the American Society for Mass Spectrometry最新文献

{"title":"Automated Pixel-Wise Recalibration for Improving Mass Accuracy and Peak Assignment in MALDI Mass Spectrometry Imaging","authors":"Yuhao Fang,&nbsp;Kai Wu,&nbsp;Sujun Yan,&nbsp;Zilong Chen,&nbsp;Xinhai Zhu","doi":"10.1021/jasms.6c00113","DOIUrl":"10.1021/jasms.6c00113","url":null,"abstract":"<p>Mass misalignment remains a major limitation in axialMALDI-TOFmass spectrometry imaging (MSI), leading to degraded mass accuracy,peak broadening, and reduced reliability of spatial molecular interpretation.Here, we present a fully automated pixel-level postacquisition recalibrationframework that improves mass alignment while preserving single-pixelspectral fidelity. The method employs a “one-pixel, one-model”strategy using high-confidence endogenous calibration reference features,combined with dynamic peak matching and RANSAC (random sample consensus)-basedrobust regression, to correct both systematic and spatially heterogeneousmass drift. Applied to a mouse brain MSI data set (<em>N</em> = 33,903 pixels), the approach reduced the median absolute masserror from 28.1 to 5.6 ppm and restored spectral compactness in averagedspectra without introducing detectable peak-shape distortion. Theimproved mass alignment enabled the use of narrower extraction windows,resulting in enhanced spatial contrast and more reliable visualizationof both high- and low-abundance lipid species. Notably, the methodfacilitated the resolution of overlapping spectral features and revealedbiologically distinct lipid distributions that were obscured in uncalibrateddata. These gains translated into improved consistency with reference-assistedannotation under stringent mass tolerances and enhanced interpretabilityin unsupervised multivariate analyses by reducing instrument-drivenvariance. The robustness and transferability of the framework werefurther demonstrated across independent data sets acquired under differentmatrix systems (DHB and NEDC), ion modes, and biological models (mousebrain and zebrafish), including data affected by substantial instrumentalinstability. In all cases, recalibration consistently reduced mass-errordispersion, improved spectral quality, and enhanced spatial signalextraction under fixed narrow-window conditions. Application of thestrategy to different MALDI-MSI platforms also demonstrated its broadapplicability and effectiveness in reducing mass errors. Overall,this pixel-level recalibration strategy provides a practical and broadlyapplicable postprocessing solution for improving mass accuracy, spectralfidelity, and spatial interpretability in MALDI-TOF MSI, thereby enablingmore reliable molecular annotation and spatial analyses on widelyaccessible instrumentation.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":"37 8","pages":"1858–1871"},"PeriodicalIF":2.9,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148387208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Persistent Homology as a Detection Axis Complementary to Intensity-Based Methods for Comparative MALDI Mass Spectrometry Imaging","authors":"Shinichi Yamaguchi,&nbsp;Yuzuki Morita,&nbsp;Hiromichi Suetani,&nbsp;Ikuko Yao","doi":"10.1021/jasms.6c00138","DOIUrl":"10.1021/jasms.6c00138","url":null,"abstract":"<p>Comparing spatial molecular distributions across massspectrometryimaging (MSI) sections is complicated by intersection shape differences,intensity variation, and the blindness of intensity-based tests tospatial organization. Persistent homology (PH) with per-section z-scorenormalization and 1-Wasserstein (W1) distance between persistencediagrams provides an alignment-free framework for quantifying spatialdissimilarity. We applied this pipeline to the public positive-modeMALDI-MSI lung lipidomics data set of Stevens et al. (2025): 12 mice(6 female, 6 male; 3 saline (SFA) and 3 HDM + O3 per sex). For eachsex, 1000 <em>m</em>/<em>z</em> channels were screenedacross 15 pairwise comparisons and prioritized by 9/9 directionalconsistency (all 9 cross-group distances exceeding the within-groupmean). The female cohort yielded 16 PH candidates (∼15 putativespecies), of which 8 have strong Moran’s I support (HO3/SFAMoran ratio ≥2 with absolute HO3Moran ≥0.20); the malecohort yielded 1 candidate, consistent with the expected sex-specificity.The Kolmogorov–Smirnov and Earth Mover’s Distance baselinesapplied to the same pair structure returned 9 and 29 female candidateswith zero overlap with the PH set at the main parameters (KS was acomplete subset of EMD); the overlap becomes partial at coarser binning.A control analysis applying EMD to z-scored pixel distributions returned92 female candidates, of which only 5 overlapped with PH and 3 withraw-EMD, localizing the detection-domain separation primarily to thetopology/W1 step rather than to z-score preprocessing alone. Withinthis positive-mode data set PH acts as a detection axis partiallyorthogonal to intensity-based screening; candidates are reported asprioritization targets requiring targeted MS/MS for identification.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":"37 8","pages":"1910–1921"},"PeriodicalIF":2.9,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148410022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Experimental Study of Collision-Induced Dissociation for Ionic Liquid Ions and Clusters","authors":"Stefan J. Bell,&nbsp;Abu Md Tahsin,&nbsp;Elaine Petro","doi":"10.1021/jasms.5c00437","DOIUrl":"10.1021/jasms.5c00437","url":null,"abstract":"<p>Electrospray ionization is well established in mass spectrometry,but the collisional behavior of electrospray ions in the context ofsatellite propulsion systems remains poorly understood. This workdemonstrates the covalent dissociation onset energy for commonly usedionic liquids, 1-ethyl 3-methylimidazolium bis(trifluoromethylsulfonyl)imide(EMI-TFSI) and 1-ethyl 3-methylimidazolium tetrafluoroborate (EMI-BF₄), using tandem mass spectrometry (MS2). Characteristic collisionproducts are identified for each ionic liquid and for their <em>n</em> = 1 ion clusters (dimers). Additionally, experimentallymeasured detection fractions for each dissociation product are reportedas a function of the lab-frame collisional energy. The experimentalresults are compared with molecular dynamics simulations to providea validation case for the simulation results.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":"37 8","pages":"1754–1763"},"PeriodicalIF":2.9,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148417778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improved Protein Identification in Native Ambient Mass Spectrometry by the Integration of Proton Transfer Charge Reduction and Higher-Energy Collision Dissociation (PTCR-HCD MS3)","authors":"Rebecca L. Edwards,&nbsp;Oliver J. Hale,&nbsp;Sarah R. W. Vickers,&nbsp;Helen J. Cooper","doi":"10.1021/jasms.6c00165","DOIUrl":"10.1021/jasms.6c00165","url":null,"abstract":"<p>Here,we demonstrate PTCR-HCD MS³ as a toolfor improvingprotein identification in native ambient mass spectrometry (NAMS).NAMS involves the direct analysis of tissue sections with no or littlesample preparation and no (solution-phase) separation postsampling.NAMS samples are therefore highly complex, comprising proteins, salts,and other biomolecules, and NAMS spectra are highly congested. PTCRMS has emerged as a useful strategy in top-down proteomics. Most commonly,it is applied as an adjunct MS² step, providing molecularweight information to support sequence information provided by collision-basedMS² or it is applied as an MS³ step to simplifycollision, photon, or electron-based MS² by reducing <em>m</em>/<em>z</em> overlap of product ions. In this work,we show that the selection of charge-reduced PTCR product ions forsubsequent HCD reduces the incidence of chimeric fragmentation spectraand improves confidence in protein identification in NAMS samplesfrom mouse spinal cord, rat kidney, and cell-line-derived xenografttissue. As well as removing interference from overlapping proteinspecies, we show that PTCR-HCD MS³ also removes interferencefrom overlapping lipid species which can similarly affect confidentprotein identification. The approach also allows identification ofproteins that are masked at the MS1 level but are revealed followingPTCR.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":"37 8","pages":"1971–1980"},"PeriodicalIF":2.9,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148468159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Uneven Distribution of Oxygen Lability within Phosphatidylserine Evaluated with Oxygen Exchange and Tandem Mass Spectrometry","authors":"Evgeny B. Serebryakov,&nbsp;Igor A. Kaltashov","doi":"10.1021/jasms.6c00053","DOIUrl":"10.1021/jasms.6c00053","url":null,"abstract":"<p>Understanding themechanism of isotope exchange between biomoleculesand solvent molecules has very important implications in two areasof life sciences, namely, the studies of biomolecular dynamics usingthe exchange of labile atoms as a structural probe and the investigationof metabolic pathways using stable isotope-labeled (SIL) compounds.While the former has benefited greatly from the fast exchange of heteroatom-boundhydrogens with water molecules, several other elements have been shownto exhibit fast-to-moderate exchange kinetics with the solvent molecules,raising the hopes that they can also be used as structural probesin isotope exchange reactions. Conversely, significant isotope exchangebetween SIL compounds and the solvent molecules in metabolic studieswould be highly detrimental vis-à-vis the reliability of quantitative(and in extreme cases also qualitative) aspects of such investigations.We use phosphatidylserine 16:0/16:0 (PS) as a model compound to probecatalyst-free oxygen exchange (¹⁶O/¹⁸O) withwater in a site-specific fashion using tandem mass spectrometry (MS/MS)as a readout. All three oxygen-containing functionalities are targeted:the carboxylate end-group, the phosphate linker, and the fatty acids’acyl ester groups (nonbridging oxygen atoms). Oxygen exchange withinboth the carboxylic moiety and the acyl ester groups is slow underthe physiologically relevant conditions but is dramatically acceleratedin acidic media at elevated temperatures. In contrast, exchange ofthe oxygen atoms within the phosphate linker remains below the limitof detection under all conditions tested in this work. While theseresults may be viewed as disappointing vis-à-vis the prospectsof using oxygen exchange to study phospholipid dynamics (e.g., toquantify PS localization on the outer membrane leaflet upon cell activationor apoptosis), they are both reassuring and helpful in the contextof studies relying on stable isotopes as tracers of metabolic processes.Indeed, the uneven distribution of oxygen lability across three differentfunctionalities, as well as the identification of conditions thatresult in oxygen exchange acceleration, will be invaluable for bothdesigning the SIL compounds and selecting the sample-handling conditionsthat eliminate the possibility of “isotope leaching”in the studies of metabolic pathways.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":"37 8","pages":"1804–1811"},"PeriodicalIF":2.9,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148409993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"KMD-Enhanced MALDI-ToF MS for Polymer Biodegradation Analysis","authors":"Sophia Y. van Mourik,&nbsp;Heather J. Walker,&nbsp;Anthony J. Ryan","doi":"10.1021/jasms.6c00101","DOIUrl":"10.1021/jasms.6c00101","url":null,"abstract":"<p>A noveland tailored mass spectrometry workflow is presented forthe analysis of polymer biodegradation products, integrating principlesfrom the ‘omics’ sciences to address the challengesof complex mixture characterization. The workflow combines methodologiesfrom polymer analysis and metabolomics, offering a comprehensive approachto data acquisition and processing, with practical considerationsfor user implementation. Central to the analytical strategy is theapplication of Kendrick Mass Defect (KMD) theory, which enhances spectralvisualization and facilitates the identification of biodegradationproducts and metabolites within heterogeneous samples. By combiningaccessible and open software tools along with custom R scripts, theworkflow supports reproducible MS data analysis, providing a platformfor advancing polymer biodegradation research. Biodegraded samples,due to their complex polymer and metabolite content, typically generatenoisy spectra, which require intensive filtering to distinguish polymerfragments from microbial metabolites. While pure polymer spectra aregenerally cleaner, they still necessitate specific peak detectionmethods, emphasizing the need for tailored data processing protocols.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":"37 8","pages":"2033–2045"},"PeriodicalIF":2.9,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148434509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Conformational Landscapes Observed through Controlled Kinetics (CLOCK): Precise Control of Ion Temperatures from Submillisecond to Second Time Scales","authors":"AnneClaire Wageman,&nbsp;Yuan Feng,&nbsp;Addison E. Roush,&nbsp;Rilke L.K. Grimlund,&nbsp;Matthew F. Bush","doi":"10.1021/jasms.6c00218","DOIUrl":"10.1021/jasms.6c00218","url":null,"abstract":"<p>A detailed understanding of ion conformational dynamicsover arange of temperatures and time scales remains a central challengein structural mass spectrometry. We recently introduced SLIMPHONY,which is a traveling-wave ion mobility (IM) instrument built on structuresfor lossless ion manipulations (SLIM), and demonstrated proof-of-conceptexperiments for conformational landscapes observed through controlledkinetics (CLOCK). Here, we develop CLOCK as a quantitative frameworkfor probing ion dynamics on submillisecond to second time scales.We apply CLOCK to native-like ions of 6+ ubiquitin and 7+ cytochrome <em>c</em> and show that both the guard electrode potential and theduration of activation independently control the resulting conformationaldistributions. We then combine ion trajectory simulations with statisticalmethods to estimate effective translational temperatures, providinga physically interpretable scale for comparing activation conditionsand a mechanistic understanding of CLOCK. Applying this temperaturecalibration to CLOCK experiments reveals that 6+ ubiquitin and 7+cytochrome <em>c</em> exhibit very distinct unfolding kineticsover a similar range of effective temperatures. Together, these resultsestablish CLOCK as a quantitative, temperature-resolved, and time-resolvedframework for probing ion conformational dynamics.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":"37 8","pages":"2023–2032"},"PeriodicalIF":2.9,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148534732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interlaboratory Comparison of Orbitrap Analyzers in OrbiSIMS: Noise Parameters, Intensity Scaling, and Detection Limits","authors":"Gustavo F. Trindade,&nbsp;Michael R. Keenan,&nbsp;Alexander Pirkl,&nbsp;Michael Fartmann,&nbsp;Yuxiao Hou,&nbsp;Christine Kern,&nbsp;Anna Kotowska,&nbsp;Karsten Lamann,&nbsp;Mina Matsuo,&nbsp;Eleonora Paladino,&nbsp;Jiawen Qiu,&nbsp;Elke Tallarek,&nbsp;Yundong Zhou,&nbsp;Marcus Rohnke,&nbsp;Lu-Tao Weng,&nbsp;Ian S. Gilmore","doi":"10.1021/jasms.6c00119","DOIUrl":"10.1021/jasms.6c00119","url":null,"abstract":"<p>Orbitrap secondary ion mass spectrometry (OrbiSIMS) combineshigh-resolutionmass analysis with surface- and depth-resolved chemical imaging, enablingconfident molecular identification across a wide range of materialsand biological systems. As the number of OrbiSIMS instruments in operationcontinues to grow, establishing reproducible and comparable performanceacross laboratories has become increasingly important. Here, we reportthe results of a Versailles Project on Advanced Materials and Standards(VAMAS) interlaboratory comparison designed to assess Orbitrap noisecharacteristics, detection limits, and intensity scale calibrationin OrbiSIMS. Using replicated spectra acquired from a common silverreference sample across ten instruments worldwide, we quantify thenoise structure of the Orbitrap analyzer and determine scaling parametersthat convert arbitrary intensity units into true ion counts. The resultsconfirm that Orbitrap noise behavior is governed by the total ionpopulation in the trap and exhibits consistent characteristics acrossinstruments and Orbitrap models operated below saturation. The ratiobetween the calibration scaling parameter and the detector noise parameter(A/σ) is shown to be largely intensity-independent in the linearregime, providing a robust metric for comparing instrument performance.From the measured noise properties, detection limits are estimatedfor each instrument, highlighting the influence of ion load and thresholdingon analytical sensitivity. In addition, instrument-specific weightedsum of Rician (WSoR) noise models are derived and shown to yield consistentscaling behavior, enabling noise-unbiased multivariate statisticalanalysis and machine learning. Together, these results establish ametrological framework for reproducible OrbiSIMS measurements, supportmeaningful cross-laboratory comparison, and provide a foundation forfuture studies addressing Orbitrap linearity and performance acrossthe full dynamic range required for advanced SIMS imaging and depth-profilingapplications. The concepts and metrics introduced are directly applicableto Orbitrap mass spectrometry more broadly and are a foundation fora robust framework that can be incorporated into QA/QC workflows.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":"37 8","pages":"1883–1889"},"PeriodicalIF":2.9,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148315200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integration of a Modified Synchrotron Radiation Photoionization Time-of-Flight Mass Spectrometer with a Residual Gas Analyzer for Complementary Detection of Catalytic Products with Different Ionization Energies","authors":"Jun Huang,&nbsp;Zhiwei Wen,&nbsp;Tianci Xiao,&nbsp;Shijun Gao,&nbsp;Guangqi Wang,&nbsp;Yihan Tang,&nbsp;Minggao Xu,&nbsp;Chengyuan Liu,&nbsp;Yang Pan","doi":"10.1021/jasms.6c00006","DOIUrl":"10.1021/jasms.6c00006","url":null,"abstract":"<p>In situ synchrotron radiation photoionization mass spectrometry(SR-PIMS) is a powerful tool for detecting gas-phase species includingintermediates and products in gas–solid catalytic reactions.However, achieving sensitive and more comprehensive monitoring ofgas-phase compounds with different ionization energies in a singlemeasurement remains a significant challenge. In this work, a multiphysicsion trajectory simulation integrating a coupled computational fluiddynamics-direct simulation Monte Carlo (CFD-DSMC) method for continuum-rarefiedflow was carried out for tracing the ion motion within the ionizationregion. The simulation results were applied to the design of the cagelens assembly of a modified SR-PIMS, and a limit of detection (LOD)of 0.67 ppbv (<em>S</em>/<em>N</em> ≥ 3) wasachieved under Kr-lamp calibration conditions for toluene. Furthermore,a residual gas analyzer (RGA) was coupled to the SR-PIMS for the complementarydetection of organic products with low ionization energies (IEs, generallylower than 11 eV) and H₂, CO, CO₂ etc. withhigher IEs, thereby reducing the need for separate measurements atmultiple photon energies. The optimized SR-PIMS setup combined withRGA was successfully applied to probe the intermediates and productsgenerated during the methanol-to-hydrocarbons (MTH) reaction overZnO/HZSM-5 catalysts, and the time-evolved profiles for major speciesunder different ZnO loadings were obtained and analyzed.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":"37 8","pages":"1773–1782"},"PeriodicalIF":2.9,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148350241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging for Spatially Resolved Food Safety Analysis","authors":"Yikang Hou,&nbsp;Zhuoxi Li,&nbsp;Jie Lian","doi":"10.1021/jasms.6c00137","DOIUrl":"10.1021/jasms.6c00137","url":null,"abstract":"<p>Food safety analysis still relies primarily on homogenization-basedchromatography and spectroscopy. These methods remain indispensablefor residue compliance and exposure assessment, but they collapseheterogeneous food structures into average concentration values. Thatlimitation becomes important when the analytical question is not onlywhether a hazardous or safety-relevant molecule is present, but alsowhere it is produced, how far it penetrates, and which tissue domainscreate local exposure hotspots. Matrix-assisted laser desorption/ionizationmass spectrometry imaging (MALDI-MSI) can address this interpretivegap by acquiring mass spectra from defined coordinates while retainingthe spatial relationship between molecular signal and food structure.This review examines MALDI-MSI specifically as a source of spatialevidence for food safety, rather than as a general food-imaging technology.The literature is classified into three evidence levels: direct food-safetyapplications, indirectly relevant quality or plant-metabolomics models,and future opportunities that still require food-matrix demonstration.Direct examples are currently strongest for surface additives andselected processing contaminants, whereas food-matrix evidence remainssparse for mycotoxins, pesticide and veterinary-drug residues, packagingmigrants, and allergens. Reported food and plant MALDI-MSI studiescommonly operate from the low tens to hundreds of micrometers in lateralresolution, but sensitivity, limits of detection, and quantitativevalidity are highly analyte- and matrix-dependent rather than transferableacross hazards. The central conclusion is therefore deliberately cautious:MALDI-MSI is not yet a replacement for validated LC-MS/MS or GC-MSregulatory assays. Its strongest current role is complementary, providingmechanistic localization, penetration profiles, hotspot mapping, andcompartment-specific descriptors that bulk methods cannot supply.Reliable use requires explicit control of low-mass matrix background,ion suppression, analyte redistribution, molecular confirmation, calibrationdesign, and orthogonal validation.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":"37 8","pages":"1705–1717"},"PeriodicalIF":2.9,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148429550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}