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But current saliva detection methods are hampered from clinical application by their restricted target diversity, complex procedures, and costly equipment. In this work, we introduce an enzymatic responsive serial\u2010nanofluids strategy, enabling simultaneous trace\u2010level detection of multiple humoral markers in saliva. Enzymatic\u2010responsive nanochannels were engineered respectively by modifying the outer surfaces of AAO arrays with polypeptides featuring target\u2010cleavage sites. Thus, the macromolecular markers in saliva could cleave corresponding polypeptide, opening the ion pathway and enhancing the ion flux of nanochannels. Upon the open of a set of nanochannel\u2010arrays tandemly connected, serial\u2010nanofluids are generated and ionic currents are coupled to enable collaborative detection of multiple targets. Employing oral cancer markers of MMP\u20101 and MMP\u20103 as models, we developed a mobile nanosensor that can concurrently monitor their trace variation low to 2.14 \u00d7 10\n                    <jats:sup>\u2212<\/jats:sup>\n                    <jats:sup>1<\/jats:sup>\n                    <jats:sup>3<\/jats:sup>\n                    g\/mL. Furthermore, the clinical trial indicated that our nanosensor could noninvasively, conveniently, and effectively distinguish healthy individuals from oral cancer patients, and those with lymph node metastasis. This strategy offers a robust framework for multi\u2010marker detection in clinical diagnostics, facilitating high\u2010frequency and large\u2010scale cancer screening through saliva test.\n                  <\/jats:p>","DOI":"10.1002\/adma.202522747","type":"journal-article","created":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T14:28:54Z","timestamp":1771597734000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Trace Detection of Multiple Macromolecular Biomarkers in Saliva by Enzymatic Responsive Serial\u2010Nanofluids Strategy"],"prefix":"10.1002","volume":"38","author":[{"given":"Nuo","family":"Chen","sequence":"first","affiliation":[{"name":"Beijing Laboratory of Biomedical Materials Department of Geriatric Dentistry Peking University School and Hospital of Stomatology  Beijing P. R. 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