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We introduce multiplex in situ tagging (MIST) Linker, a rapid and Fc-site-specific labeling tool that conjugates fluorophores or DNA oligonucleotides to antibodies from diverse commercial sources in as fast as 10 min using minimal starting material. MIST Linker achieves &gt;90% cleavage upon UV exposure, facilitating rapid cyclic imaging on a single specimen. Validated across multiple species and sources, the platform outperforms conventional two-step immunofluorescence and immunohistochemistry in various tissues and cell lines. By enabling the rapid, cost-effective customization of antibody panels, MIST Linker significantly lowers the barrier to accessing antibody\u2013DNA conjugates for spatial biology. When integrated with the spatial MIST platform and MIST-Explorer, it enables high-plex, single-cell spatial proteomics at high signal-to-noise ratios in human clinical biopsies, mouse specimens and cell lines. This toolkit provides an efficient, accessible solution for high-resolution spatial mapping, allowing for the in-depth analysis of cell subpopulations, biomarker distributions, and signaling events in complex biological specimens. Thus, MIST Linker offers a versatile, accessible, and scalable solution for antibody-labeling-based research and clinical diagnosis.<\/jats:p>","DOI":"10.3390\/bios16070385","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T03:34:23Z","timestamp":1784172863000},"page":"385","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Universal, Rapid, and Cleavable Labeling of Antibodies by Fluorophores and DNA Oligonucleotides for Multiplex Immunostaining and Spatial Proteomics Through MIST Linker"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-4908-6523","authenticated-orcid":false,"given":"Arafat","family":"Meah","sequence":"first","affiliation":[{"name":"Multiplex Biotechnology Laboratory, Department of Biomedical Engineering, State University of New York at Stony Brook, Stony Brook, NY 11794, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4273-7839","authenticated-orcid":false,"given":"Shuo","family":"Yin","sequence":"additional","affiliation":[{"name":"Multiplex Biotechnology Laboratory, Department of Biomedical Engineering, State University of New York at Stony Brook, Stony Brook, NY 11794, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saimoen Strrrz","family":"Anderson","sequence":"additional","affiliation":[{"name":"Multiplex Biotechnology Laboratory, Department of Biomedical Engineering, State University of New York at Stony Brook, Stony Brook, NY 11794, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3481-7066","authenticated-orcid":false,"given":"Ming","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Computer Science, State University of New York at Stony Brook, Stony Brook, NY 11794, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuo","family":"Liang","sequence":"additional","affiliation":[{"name":"Multiplex Biotechnology Laboratory, Department of Biomedical Engineering, State University of New York at Stony Brook, Stony Brook, NY 11794, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meghana","family":"Davuluri","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, State University of New York at Stony Brook, Stony Brook, NY 11794, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Xian","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, State University of New York at Stony Brook, Stony Brook, NY 11794, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandeep K.","family":"Mallipattu","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Department of Medicine, Stony Brook School of Medicine, Stony Brook, NY 11794, USA"},{"name":"Renal Section, Northport VA Medical Center, Northport, NY 11768, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Wang","sequence":"additional","affiliation":[{"name":"Multiplex Biotechnology Laboratory, Department of Biomedical Engineering, State University of New York at Stony Brook, Stony Brook, NY 11794, USA"},{"name":"MIST Bioscience, New York, NY 11794, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1038\/s41392-023-01379-7","article-title":"Kidney fibrosis: From mechanisms to therapeutic medicines","volume":"8","author":"Huang","year":"2023","journal-title":"Signal Transduct. 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