{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T13:56:33Z","timestamp":1790690193688,"version":"4.1.0"},"reference-count":32,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100005046","name":"Natural Science Foundation of Heilongjiang Province","doi-asserted-by":"publisher","award":["JJ2024YX0618"],"award-info":[{"award-number":["JJ2024YX0618"]}],"id":[{"id":"10.13039\/501100005046","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Small"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Point\u2010of\u2010care compatible therapeutic drug monitoring requires platforms to rapidly quantify low\u2010abundance small\u2010molecule drugs in complex biofluids while resolving spectral interference from coexisting compounds. Surface\u2010enhanced Raman spectroscopy offers molecular fingerprint specificity, yet its quantitative reliability is often compromised by heterogeneous hotspots, matrix interference, and overlapping drug spectra. Here, we develop an integrated microfluidic SERS platform based on charge\u2010directed 3D Au@Ag plasmonic assemblies and machine learning\u2010assisted spectral decoding. Oppositely charged gold nanopolytopes and silver nanospheres spontaneously assemble into ordered 3D structures with dense interparticle nanogaps. Optimized 1:1 Au@Ag assembly delivers enhanced electromagnetic coupling and stable, reproducible SERS signals. Combined with deuterated methanol as a ratiometric internal standard in microfluidic chips, this system achieves low\u2010volume, fluctuation\u2010corrected standardized drug analysis. Six therapeutic molecules are identified via SERS fingerprints, and binary or ternary mixtures are accurately decoded by 3D\u2010LDA and CNN\u2010RF with AUC &gt; 0.98. Reliable discrimination in rat plasma, artificial sweat, and urine demonstrates excellent matrix tolerance. This work establishes a material microfluidic algorithm\u2010integrated SERS strategy for rapid therapeutic drug analysis, paving the way toward portable intelligent drug monitoring systems.<\/jats:p>","DOI":"10.1002\/smll.75991","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T13:05:22Z","timestamp":1790687122000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Machine\u2010Learning\u2010Enabled Microfluidic SERS With Charge\u2010Directed 3D Au@Ag Plasmonic Assemblies for Therapeutic Drug Monitoring in Complex Biofluids"],"prefix":"10.1002","author":[{"given":"Yanlong","family":"Xiao","sequence":"first","affiliation":[{"name":"The Second Hospital of Jilin University Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ran","family":"Gao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD) Research Center for Innovative Technology of Pharmaceutical Analysis College of Pharmacy Harbin Medical University  Harbin City Heilongjiang Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaochao","family":"Ma","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD) Research Center for Innovative Technology of Pharmaceutical Analysis College of Pharmacy Harbin Medical University  Harbin City Heilongjiang Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangrui","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD) Research Center for Innovative Technology of Pharmaceutical Analysis College of Pharmacy Harbin Medical University  Harbin City Heilongjiang Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Jiang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD) Research Center for Innovative Technology of Pharmaceutical Analysis College of Pharmacy Harbin Medical University  Harbin City Heilongjiang Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiacheng","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD) Research Center for Innovative Technology of Pharmaceutical Analysis College of Pharmacy Harbin Medical University  Harbin City Heilongjiang Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaowen","family":"Xing","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD) Research Center for Innovative Technology of Pharmaceutical Analysis College of Pharmacy Harbin Medical University  Harbin City Heilongjiang Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD) Research Center for Innovative Technology of Pharmaceutical Analysis College of Pharmacy Harbin Medical University  Harbin City Heilongjiang Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD) Research Center for Innovative Technology of Pharmaceutical Analysis College of Pharmacy Harbin Medical University  Harbin City Heilongjiang Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Physical Science and Technology Nantong University  Nantong Jiangsu People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD) Research Center for Innovative Technology of Pharmaceutical Analysis College of Pharmacy Harbin Medical University  Harbin City Heilongjiang Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixin","family":"Guo","sequence":"additional","affiliation":[{"name":"The Second Hospital of Jilin University Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0677-3245","authenticated-orcid":false,"given":"Yang","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD) Research Center for Innovative Technology of Pharmaceutical Analysis College of Pharmacy Harbin Medical University  Harbin City Heilongjiang Province China"},{"name":"Research Unit of Health Sciences and Technology (HST) Faculty of Medicine University of Oulu  Oulu Finland"},{"name":"Inpatient Department Heilongjiang Provincial Eye Hospital  Harbin City Heilongjiang Province China"},{"name":"Heilongjiang Provincial Clinical Medical Research Center For Chemical Poisoning Heilongjiang Second Provincial Hospital  Harbin City Heilongjiang Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,29]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-2667(26)00007-1"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2026.2197"},{"key":"e_1_2_9_4_1","first-page":"ehaf784","article-title":"Human Papillomavirus Infection and Risk of Cardiovascular Disease","volume":"46","author":"Deng Y.","year":"2026","journal-title":"European Heart 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