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Found in biofluids like saliva, urine, blood, and peritoneal fluid, EVs serve as promising minimally invasive biomarkers for several conditions including cancer.\u00a0However, achieving high sensitivity and specificity in EV detection remains technically challenging. Placental Alkaline Phosphatase (PLAP), an enzyme primarily expressed in the placenta during pregnancy, has emerged as a clinically relevant biomarker in gynecological malignancies, including ovarian cancer (OC). In this study, a nanoengineered mesoporous gold (mAu)\u2010based Surface\u2010Enhanced Raman Spectroscopy (SERS) platform is reported for the rapid and ultrasensitive detection of PLAP\u2010positive EVs in OC patients. The mAu\u00a0offers high surface roughness, enabling numerous localized plasmonic hotspots that amplify Raman signals and improve probe and antibody loading. This allowed the detection of as few as 100 EVs\u00a0mL<jats:sup>\u22121<\/jats:sup> with excellent reproducibility (RSD\u00a0&lt;\u00a05%,n = 3). In clinical validation (n = 30), the assay achieved 90% sensitivity (<jats:italic>95% CI: 60%\u2013100%)<\/jats:italic> and 85% specificity (<jats:italic>95% CI: 15%\u2013100%<\/jats:italic>) in distinguishing OC patients from those with benign and healthy controls,\u00a0demonstrating superior performance compared to CA\u2010125. The mAu\u2010SERS platform shows considerable promise as a minimally invasive and clinically applicable diagnostic strategy for OC, especially for differential diagnosis for their ability to distingluis between benign and OC conditions.<\/jats:p>","DOI":"10.1002\/smll.202401817","type":"journal-article","created":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T05:14:57Z","timestamp":1752124497000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Plasmonic Mesoporous Gold\u2010Based SERS Biosensor for Ovarian Cancer\u2010Derived Extracellular Vesicles"],"prefix":"10.1002","volume":"21","author":[{"given":"Javeria","family":"Bashir","sequence":"first","affiliation":[{"name":"School of Mechanical and Mining Engineering Faculty of Engineering Architecture, and Information Technology (EAIT) The University of Queensland  Brisbane Queensland 4072 Australia"},{"name":"Australian Institute for Bioengineering and 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