{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T12:13:01Z","timestamp":1788437581012,"version":"build-2803163510"},"reference-count":38,"publisher":"American Chemical Society (ACS)","issue":"34","license":[{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Mass spectrometry imaging (MSI) is a powerful technique for visualizing the spatial distribution of chemical species in biological samples. Time-of-flight secondary ion mass spectrometry (TOF-SIMS) enables high-spatial-resolution imaging and the detection of a broad range of molecular ions, including intact lipids. However, the observation of high-mass components remains challenging due to limitations in ionization efficiency and sample degradation. In this study, we present a novel sample preparation method for TOF-SIMS using an ionic liquid (IL) pretreatment to enhance the ionization efficiency of high-mass lipid ions. This approach increases the ionization efficiency of lipid molecules by achieving an appropriate distribution of ionic liquid to the surface of the sample. By reducing fragmentation, this method exceeds the static limit and increases the lipid ion signal by nearly 3 orders of magnitude. Furthermore, this method enabled static TOF-SIMS imaging of lipid-related ions and ion-induced electron imaging beyond the conventional static limit. These advancements significantly improve TOF-SIMS-based MSI applications, offering new opportunities for lipidomics and biological research.<\/jats:p>","DOI":"10.1021\/acsomega.6c03014","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T10:02:03Z","timestamp":1787047323000},"page":"51034-51041","source":"Crossref","is-referenced-by-count":0,"title":["TOF-SIMS Imaging\nof Intact Lipids in Biological Tissue\nwith Enhanced Ion Intensity by Ionic Liquid"],"prefix":"10.1021","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-3259-555X","authenticated-orcid":true,"given":"Itsuko","family":"Ishizaki","sequence":"first","affiliation":[{"name":"ULVAC-PHI, Inc. , 2500 Hagisono, , ,","place":["Chigasaki, Kanagawa, Japan, 253-8522"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriaki","family":"Sanada","sequence":"additional","affiliation":[{"name":"ULVAC-PHI, Inc. , 2500 Hagisono, , ,","place":["Chigasaki, Kanagawa, Japan, 253-8522"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,18]]},"reference":[{"issue":"1","key":"2026090307171498500_cit1","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1007\/s00216-008-2367-3","article-title":"Lipid imaging with cluster time-of-flight secondary\nion mass spectrometry","volume":"393","author":"Brunelle","year":"2009","journal-title":"Anal. Bioanal. Chem."},{"key":"2026090307171498500_cit2","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/j.jprot.2014.03.021","article-title":"MALDI imaging\nmass spectrometry:\nspatial molecular analysis to enable a new age of discovery","volume":"107","author":"Gessel","year":"2014","journal-title":"J. Proteomics"},{"key":"2026090307171498500_cit3","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1038\/s43586-024-00311-9","article-title":"Secondary\nion mass spectrometry","volume":"4","author":"Lockyer","year":"2024","journal-title":"Nat. Rev. Methods Primers"},{"issue":"3","key":"2026090307171498500_cit4","doi-asserted-by":"publisher","first-page":"03B411","DOI":"10.1116\/1.5019611","article-title":"Molecular\ndepth profiling on rat brain tissue sections prepared using different\nsampling methods","volume":"13","author":"Shon","year":"2018","journal-title":"Biointerphases"},{"issue":"8","key":"2026090307171498500_cit5","doi-asserted-by":"publisher","first-page":"1230","DOI":"10.1016\/j.jasms.2008.05.006","article-title":"Preparation of single cells for imaging\/profiling\nmass spectrometry","volume":"19","author":"Berman","year":"2008","journal-title":"J. Am. Soc. Mass Spectrom."},{"issue":"6","key":"2026090307171498500_cit6","doi-asserted-by":"publisher","first-page":"1550","DOI":"10.1021\/ac035243z","article-title":"Tissue molecular ion imaging by gold\ncluster ion bombardment","volume":"76","author":"Touboul","year":"2004","journal-title":"Anal. 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Soc.\nMass Spectrom."},{"issue":"1\u20132","key":"2026090307171498500_cit9","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1016\/j.ijms.2006.11.003","article-title":"Enhanced secondary ion emission with\na bismuth cluster\nion source","volume":"262","author":"Nagy","year":"2007","journal-title":"Int. J. Mass Spectrom."},{"issue":"12","key":"2026090307171498500_cit10","doi-asserted-by":"publisher","first-page":"5654","DOI":"10.1021\/ac4013732","article-title":"Enhancing\nsecondary ion yields in time-of-flight secondary ion mass spectrometry\nusing water cluster primary beams","volume":"85","author":"Sheraz","year":"2013","journal-title":"Anal. 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Mass Spectrom."},{"issue":"19","key":"2026090307171498500_cit14","doi-asserted-by":"publisher","first-page":"6966","DOI":"10.1016\/j.apsusc.2006.02.126","article-title":"Localization of lipids in freeze-dried\nmouse brain sections by imaging ToF-SIMS","volume":"252","author":"Sjo\u0308vall","year":"2006","journal-title":"Appl.\nSurf. Sci."},{"issue":"20","key":"2026090307171498500_cit15","doi-asserted-by":"publisher","first-page":"1851","DOI":"10.1002\/rcm.7285","article-title":"Mass spectrometric\nimaging of brain tissue by time-of-flight secondary ion mass spectrometry\u2500How\ndo polyatomic primary beams C60+, Ar2000+, water-doped Ar2000+, and\n(H2O)6000+ compare?","volume":"29","author":"Berrueta Razo","year":"2015","journal-title":"Rapid Commun. Mass Spectrom."},{"issue":"21","key":"2026090307171498500_cit16","doi-asserted-by":"publisher","first-page":"7921","DOI":"10.1021\/ac801712s","article-title":"C60 SIMS\nwith a hybrid-quadrupole orthogonal time-of-flight\nmass spectrometer","volume":"80","author":"Carado","year":"2008","journal-title":"Anal. Chem."},{"key":"2026090307171498500_cit17","doi-asserted-by":"publisher","first-page":"1000","DOI":"10.1038\/srep10000","article-title":"Three-dimensional\nimage of cleavage\nbodies in nuclei is configured using gas cluster ion beam with time-of-flight\nsecondary ion mass spectrometry","volume":"5","author":"Masaki","year":"2015","journal-title":"Sci. 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Mass Spectrom."},{"issue":"6","key":"2026090307171498500_cit31","doi-asserted-by":"publisher","first-page":"3469","DOI":"10.1021\/acs.analchem.4c05747","article-title":"Mass Spectrometry Imaging with Matrix-Enhanced\nSIMS: The Influence of Matrix Deposition Rate on Crystal Size and\nSignal Enhancement","volume":"97","author":"Adolphs","year":"2025","journal-title":"Anal. Chem."},{"issue":"2","key":"2026090307171498500_cit32","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1021\/jasms.2c00261","article-title":"Influence of Matrix pKa on Molecular Ion Formation in Matrix-Enhanced Secondary-Ion\nMass Spectrometry","volume":"34","author":"Pohkrel","year":"2023","journal-title":"J. Am. Soc. 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Chem."},{"issue":"2","key":"2026090307171498500_cit35","doi-asserted-by":"publisher","first-page":"100","DOI":"10.11410\/kenbikyo.48.2_100","article-title":"Application\nof ionic liquid as a liquid conductive material to electron microscopy","volume":"48","author":"Kuwabata","year":"2013","journal-title":"Kenbikyo"},{"issue":"6","key":"2026090307171498500_cit36","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1093\/jmicro\/dfac035","article-title":"Verification of permeability\nfor\nionic liquid into biological specimens by using a mass spectrometer","volume":"71","author":"Yamashita","year":"2022","journal-title":"Microscopy"},{"key":"2026090307171498500_cit37","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1186\/s13568-015-0097-4","article-title":"Simple observation\nof Streptococcus mutans biofilm by scanning electron\nmicroscopy using ionic liquids","volume":"5","author":"Asahi","year":"2015","journal-title":"AMB Express"},{"issue":"1","key":"2026090307171498500_cit38","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1021\/ac202713k","article-title":"Exploring the Surface\nSensitivity\nof Tof-SIMS by Measuring the Implantation and Sampling Depths of Bin\nand C60 Ions in Organic Films","volume":"84","author":"Munemoto","year":"2012","journal-title":"Anal. 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