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However, when it comes to biomarker discovery or histopathological diagnostics, more sensitive and in-depth profiling from localized areas is required. We developed a comprehensive, fully automated online platform for high-resolution liquid extraction surface analysis (HR-LESA) followed by micro\u2013liquid chromatography (LC) separation and a data-independent acquisition strategy for untargeted and low abundant analyte identification directly from tissue sections. Applied to tissue sections of rat pituitary, the platform demonstrated improved spatial resolution, allowing sample areas as small as 400 \u03bcm to be studied, a major advantage over conventional LESA. The platform integrates an online buffer exchange and washing step for removal of salts and other endogenous contamination that originates from local tissue extraction. Our carry over\u2013free platform showed high reproducibility, with an interextraction variability below 30%. Another strength of the platform is the additional selectivity provided by a postsampling gas-phase ion mobility separation. This allowed distinguishing coeluted isobaric compounds without requiring additional separation time. Furthermore, we identified untargeted and low-abundance analytes, including neuropeptides deriving from the pro-opiomelanocortin precursor protein and localized a specific area of the pituitary gland (i.e., adenohypophysis) known to secrete neuropeptides and other small metabolites related to development, growth, and metabolism. This platform can thus be applied for the in-depth study of small samples of complex tissues with histologic features of \u223c400 \u03bcm or more, including potential neuropeptide markers involved in many diseases such as neurodegenerative diseases, obesity, bulimia, and anorexia nervosa.<\/jats:p>","DOI":"10.1021\/acs.analchem.7b03512","type":"journal-article","created":{"date-parts":[[2017,9,25]],"date-time":"2017-09-25T13:17:43Z","timestamp":1506345463000},"page":"11143-11150","source":"Crossref","is-referenced-by-count":34,"title":["Integration of Ion Mobility MSE after Fully\nAutomated, Online, High-Resolution Liquid Extraction Surface Analysis\nMicro-Liquid Chromatography"],"prefix":"10.1021","volume":"89","author":[{"given":"Lieke","family":"Lamont","sequence":"first","affiliation":[{"name":"Maastricht University , , ,","place":["Maastricht, The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Baumert","sequence":"additional","affiliation":[{"name":"Advion , ,","place":["Harlow, United Kingdom, CM20 2NQ"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Ogrinc Potoc\u030cnik","sequence":"additional","affiliation":[{"name":"Maastricht University , , ,","place":["Maastricht, The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Allen","sequence":"additional","affiliation":[{"name":"Advion , ,","place":["Harlow, United Kingdom, CM20 2NQ"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rob","family":"Vreeken","sequence":"additional","affiliation":[{"name":"Maastricht University , , ,","place":["Maastricht, The Netherlands"]},{"name":"Janssen Pharmaceutica , ,","place":["Beerse, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6533-7179","authenticated-orcid":true,"given":"Ron M. 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