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However, the lack of rapid and comprehensive characterization techniques for EV preparation analysis, coupled with the absence of efficient quality control methods, significantly hinders process optimization and large\u2010scale production. To address these challenges, we developed a label\u2010free clustering analysis (LFCA) platform that integrates nano\u2010flow cytometry for particle size distribution analysis with a clustering algorithm to deconvolute EV subpopulations and distinguish them from impurities. This platform enables the rapid quantification of EV component distribution and composition within 5 min using minimal sample input. Leveraging the high\u2010throughput capabilities of LFCA, we established a cascaded workflow incorporating a microcarrier\u2010based 3D culture system, a custom tangential flow filtration device, and multimodal size exclusion chromatography for EV preparation from adipose mesenchymal stem cells. This approach achieves a 4\u2010fold increase in EV yield compared to ultracentrifugation while maintaining comparable purity and preserving EV integrity. Critically, the resulting EVs exhibited enhanced functional potency in pro\u2010angiogenic and anti\u2010inflammatory assays, confirming the clinical relevance of our optimized production system. These advancements provide a scalable solution for EV production, paving the way for clinical applications.<\/jats:p>","DOI":"10.1002\/jev2.70333","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T04:30:54Z","timestamp":1782275454000},"source":"Crossref","is-referenced-by-count":2,"title":["Label\u2010Free Clustering Analysis Platform Drives Cascaded Workflow for Scalable Production of Therapeutic Extracellular Vesicles"],"prefix":"10.1002","volume":"15","author":[{"given":"Jing","family":"Zhou","sequence":"first","affiliation":[{"name":"Discipline of Intelligent Instrument and Equipment, College of Chemistry and Chemical Engineering Xiamen University  Xiamen Fujian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Chemical Biology, MOE Key Laboratory of Spectrochemical Analysis &amp; Instrumentation, Key Laboratory for Chemical Biology of Fujian 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