{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T18:16:59Z","timestamp":1788459419461,"version":"build-2803163510"},"reference-count":40,"publisher":"National Academy of Sciences","issue":"36","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK137113"],"award-info":[{"award-number":["DK137113"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,9,8]]},"abstract":"<jats:p>\n                    Whole-tissue level spatial proteomics provides critical insights into region-specific biological regulations but remains challenging. Previously, we introduced the micro-scaffold assisted spatial proteomics (MASP) concept for whole-tissue mapping. However, this prototype required substantial development in spatial resolution, practicality, and throughput for practical application. Here we present a next-generation MASP technique (\n                    <jats:italic toggle=\"yes\">hex-<\/jats:italic>\n                    MASP) featuring i) a new design of hexagonal-micro-wells fabricated with optimized projection micro-stereolithography 3D-printing, achieving high spatial resolution, sampling robustness, and mechanical strength for reproducibly compartmentalizing even tough tissues; ii) enhanced throughput\/effectiveness in sample preparation and LC\u2013MS analysis with high quantitative quality. Applied to mouse brain,\n                    <jats:italic toggle=\"yes\">hex-<\/jats:italic>\n                    MASP achieved in-depth, whole-tissue mapping for &gt;6,000 proteins in mouse brains, with high spatial accuracy and excellent data quality. The substantially improved resolution revealed critical regional details across the entire brain, that were not previously captured, enabling precise depiction of protein distribution heterogeneity. This technique enabled the identification of many unreported regionally enriched proteins across brain structures. We further applied\n                    <jats:italic toggle=\"yes\">hex-<\/jats:italic>\n                    MASP to investigate the intrabrain distribution of intracerebroventricularly dosed antibody therapeutics and related proteins, which enabled whole-tissue mapping of protein drugs revealed insights into antibody brain penetration and distribution.\n                    <jats:italic toggle=\"yes\">Hex<\/jats:italic>\n                    -MASP represents a robust, scalable platform for whole-tissue spatial proteomics.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2532946123","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T17:36:55Z","timestamp":1788457015000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":0,"title":["<i>Hex<\/i>\n                    -MASP for mapping the whole-tissue spatial proteome and the intrabrain distribution of monoclonal antibodies"],"prefix":"10.1073","volume":"123","author":[{"given":"Shihan","family":"Huo","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01q1z8k08","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pharmaceutical Sciences, State University of New York at Buffalo","place":["Buffalo"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Ma","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01q1z8k08","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pharmaceutical Sciences, State University of New York at Buffalo","place":["Buffalo"]},{"id":[{"id":"https:\/\/ror.org\/0499dwk57","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Cell Stress Biology, Roswell Park Comprehensive Cancer Center","place":["Buffalo"]},{"name":"Center of Excellence in Bioinformatics & Life 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New York at Buffalo","place":["Buffalo"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2004-5022","authenticated-orcid":false,"given":"Tara","family":"Barone","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0499dwk57","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Neuro-Oncology, Roswell Park Comprehensive Cancer Center","place":["Buffalo"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9388-9876","authenticated-orcid":false,"given":"Robert","family":"Plunkett","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0499dwk57","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Neuro-Oncology, Roswell Park Comprehensive Cancer 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