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EVs are nanosized (30\u2013200 nm), carriers of biomolecules that participate in cellular communication and can deliver therapeutic cargo in a targeted manner. Their use as drug vectors requires high-purity isolates; however, achieving such purity is challenging due to complex host matrices. Size exclusion chromatography (SEC) affects separations based on hydrodynamic radii and is a common isolation method due to its downstream applicability; however, it struggles to yield high-purity isolates. Polyester (PET) capillary-channeled polymer (C-CP) fiber spin-down tips are a novel EV separation platform employing hydrophobic interaction chromatography (HIC) to isolate high-purity EVs. Samples are loaded under high ionic strength conditions, where hydrophobic species adsorb to the fibers, and polar species pass through unretained. Analytes are then eluted in order of increasing hydrophobicity using an inverse salt gradient and adding small amounts of organic solvent at each step. A practical comparison of a commercial SEC column and PET C-CP spin-down tip EV eluates is conducted here via quantitative absorbance response curves, protein assays, nanoflow cytometry, and transmission electron microscopy. PET C-CP fiber platforms isolated 4.3\u2009\u00d7\u200910\n                    <jats:sup>11<\/jats:sup>\n                    particles mL\n                    <jats:sup>\u22121<\/jats:sup>\n                    of HEK supernatant and yielded purities of 3.1\u2009\u00d7\u200910\n                    <jats:sup>10<\/jats:sup>\n                    particles \u00b5g\n                    <jats:sup>\u22121<\/jats:sup>\n                    protein, a tenfold improvement for both metrics versus the SEC methodology, demonstrating a rapid, high-purity alternative to that commercial method.\n                  <\/jats:p>","DOI":"10.1007\/s00216-026-06653-5","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T11:21:08Z","timestamp":1783596068000},"page":"6307-6318","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Comparison of polyester (PET) capillary-channeled polymer (C-CP) fiber spin-down tips and size exclusion chromatography (SEC) for the isolation of HEK 293-derived extracellular vesicles (EVs)"],"prefix":"10.1007","volume":"418","author":[{"given":"Carolina","family":"Mata","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher D.","family":"Topper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4276-5805","authenticated-orcid":false,"given":"R. 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