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Here, we present a streamlined workflow for ultratrace plasma sample proteomics (UPSP) utilizing boronic acid-functionalized metal\u2013organic frameworks (MOFs) that enable efficient protein enrichment from just 1 \u03bcL plasma through synergistic nitrogen\u2013boronate complexation, cation\u2212\u03c0 interaction, and O\u2013Eu coordination. UPSP eliminates the need for high-abundance protein depletion and peptide fractionation, achieving robust and reproducible quantification of over 500 proteins per microliter with high interassay precision (R2 = 0.986) and low variability (CV &amp;lt; 20% for &amp;gt;65% of proteins). We demonstrate the utility of UPSP in a clinical context by profiling plasma from triple-negative breast cancer (TNBC) and healthy controls. Integrated with machine learning, the platform achieved a diagnostic accuracy of 0.93 for TNBC. UPSP provides a versatile and scalable platform for deep proteome profiling of trace-volume biospecimens, with broad applicability in biomarker discovery, longitudinal monitoring, and scarce-sample scenarios.<\/jats:p>","DOI":"10.1021\/acs.analchem.6c01607","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T06:13:31Z","timestamp":1784182411000},"page":"21353-21366","source":"Crossref","is-referenced-by-count":0,"title":["Boronic Acid-Functionalized\nMOFs Enable Ultrasensitive\nProteomic Profiling of Ultratrace Plasma for Triple-Negative Breast\nCancer Diagnosis"],"prefix":"10.1021","volume":"98","author":[{"given":"Shuang","family":"Zhang","sequence":"first","affiliation":[{"name":"Shanghai Jiao Tong University , , ,","place":["Shanghai, People\u2019s Republic of China, 200030"]},{"name":"Shanghai Jiao Tong University , , ,","place":["Shanghai, People\u2019s Republic of China, 200030"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhixiao","family":"Xu","sequence":"additional","affiliation":[{"name":"Shanghai Jiao Tong University , , ,","place":["Shanghai, People\u2019s Republic of China, 200030"]},{"name":"Shanghai Jiao Tong University , , ,","place":["Shanghai, People\u2019s Republic of China, 200030"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoni","family":"Yan","sequence":"additional","affiliation":[{"name":"Shanghai Jiao Tong University , , ,","place":["Shanghai, People\u2019s Republic of China, 200030"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujie","family":"Shi","sequence":"additional","affiliation":[{"name":"Shanghai Jiao Tong University , , ,","place":["Shanghai, People\u2019s Republic of China, 200030"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinwen","family":"Ding","sequence":"additional","affiliation":[{"name":"Shanghai Jiao Tong University , , ,","place":["Shanghai, People\u2019s Republic of China, 200030"]},{"name":"Shanghai Jiao Tong University , , ,","place":["Shanghai, People\u2019s Republic of China, 200030"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangxia","family":"Shen","sequence":"additional","affiliation":[{"name":"Shanghai Jiao Tong University , , ,","place":["Shanghai, People\u2019s Republic of China, 200030"]},{"name":"Shanghai Jiao Tong University , , ,","place":["Shanghai, People\u2019s Republic of China, 200030"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lai","family":"Jiang","sequence":"additional","affiliation":[{"name":"Shanghai Jiao Tong University , , ,","place":["Shanghai, People\u2019s Republic of China, 200030"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1549-3499","authenticated-orcid":true,"given":"Xianting","family":"Ding","sequence":"additional","affiliation":[{"name":"Shanghai Jiao Tong University , , ,","place":["Shanghai, People\u2019s Republic of China, 200030"]},{"name":"Shanghai Jiao Tong University , , ,","place":["Shanghai, People\u2019s Republic of China, 200030"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,7,16]]},"reference":[{"issue":"6404","key":"2026072808082222100_cit1","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1126\/science.aaq1327","article-title":"Co-regulatory\nnetworks of human serum proteins link genetics to disease","volume":"361","author":"Emilsson","year":"2018","journal-title":"Science"},{"issue":"4","key":"2026072808082222100_cit2","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.1021\/pr0500657","article-title":"Utilizing Human\nBlood Plasma for\nProteomic Biomarker Discovery","volume":"4","author":"Jacobs","year":"2005","journal-title":"J. Proteome Res."},{"issue":"8","key":"2026072808082222100_cit3","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1038\/nbt1235","article-title":"Protein\nbiomarker discovery and validation:\nthe long and uncertain path to clinical utility","volume":"24","author":"Rifai","year":"2006","journal-title":"Nat. Biotechnol."},{"issue":"3","key":"2026072808082222100_cit4","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1016\/j.cels.2016.02.015","article-title":"Plasma Proteome Profiling to Assess Human Health and Disease","volume":"2","author":"Geyer","year":"2016","journal-title":"Cell Syst."},{"issue":"1","key":"2026072808082222100_cit5","doi-asserted-by":"publisher","first-page":"946","DOI":"10.1038\/s41467-022-28639-4","article-title":"Prognostic tools and candidate drugs based on plasma\nproteomics of patients with severe COVID-19 complications","volume":"13","author":"Al-Nesf","year":"2022","journal-title":"Nat. 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