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We present SAFE (Sonication\u2010Assisted liposome Fusion with Extracellular vesicles (EVs)), a rapid, direct\u2010from\u2010plasma assay that quantifies microRNAs (miRNAs) encapsulated within EVs in approximately 10 min, providing a molecular signature of myocardial injury. SAFE delivers molecular beacons (MBs) into endogenous EVs through liposome fusion, eliminating the need for EV isolation and RNA extraction while minimizing interference from plasma proteins by confining hybridization within the EV lumen. Brief sonication accelerates fusion kinetics, shortening the assay time to 10 min. In a pilot clinical evaluation involving patients with CVD (\n                    <jats:italic>n<\/jats:italic>\n                    = 20) and healthy controls (\n                    <jats:italic>n<\/jats:italic>\n                    = 15), SAFE detected elevated levels of two cardiac\u2010associated miRNAs (miR\u2010133a and miR\u2010208a), achieving a diagnostic accuracy of 91.4% for each. These findings position SAFE as a rapid and minimally processed platform for the direct quantification of EV\u2010associated miRNAs, well suited for time\u2010critical CVD triage and ready for implementation studies across diverse clinical environments.\n                  <\/jats:p>","DOI":"10.1002\/smll.74300","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T08:55:25Z","timestamp":1782291325000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["SAFE: a Mix\u2010and\u2010Read Assay for miRNA Detection in Extracellular Vesicles From Unprocessed Plasma Toward Clinical Disease Diagnosis"],"prefix":"10.1002","volume":"22","author":[{"given":"Subhra Sulipta","family":"Jena","sequence":"first","affiliation":[{"name":"Department of Physics and Chemistry Daegu Gyeongbuk Institute of Science and Technology (DGIST)  Daegu Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soo Jin","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Asan Medical Center University of Ulsan College of Medicine  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyeonha","family":"Jang","sequence":"additional","affiliation":[{"name":"Colorectal Cancer Center Kyungpook National University Chilgok Hospital School of Medicine Kyungpook National University  Daegu Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianhua","family":"Chi","sequence":"additional","affiliation":[{"name":"Department of Physics and Chemistry Daegu Gyeongbuk Institute of Science and Technology (DGIST)  Daegu Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunji","family":"Eom","sequence":"additional","affiliation":[{"name":"Nano Lithography and Manufacturing Research Center Korea Institute of Machinery &amp; Materials  Daejeon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung\u2010Oh","family":"Doh","sequence":"additional","affiliation":[{"name":"Department of Physiology Yeungnam University College of Medicine  Daegu Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JaeJong","family":"Lee","sequence":"additional","affiliation":[{"name":"Nano Lithography and Manufacturing Research Center Korea Institute of Machinery &amp; Materials  Daejeon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun Seok","family":"Park","sequence":"additional","affiliation":[{"name":"Colorectal Cancer Center Kyungpook National University Chilgok Hospital School of Medicine Kyungpook National University  Daegu Republic of Korea"},{"name":"Department of Surgery School of Medicine Kyungpook National University  Daegu Republic of 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