Whole-Blood Extracellular Vesicle Analysis Captures Molecular Signals Missed by Plasma Testing

Extracellular vesicles (EVs) carry proteins and lipids that reflect cell states and disease processes, but their analysis typically depends on plasma or serum. This excludes signals originally present in whole blood and may limit clinical biomarker discovery. Meanwhile, biobanks worldwide store large numbers of whole-blood samples that remain underused for EV research. A new study shows that directly isolating circulating EVs from whole blood can recover complementary molecular information.

At IRBLleida’s +Pec Proteomics Research Group and the University of Lleida, together with Brock University and Newcastle University, researchers optimized the PRotein Organic Solvent PRecipitation (PROSPR) method for standardized enrichment of EVs directly from whole blood. PROSPR uses protein organic solvent precipitation to rapidly concentrate circulating vesicles. The workflow generated highly purified EV preparations while preserving vesicle morphology, membrane integrity, and stability.

Performance was validated using standard methodology in the field and then assessed with high-depth systems biology and multiomics analyses. The method was described as rapid and accessible, and it is compatible with standard laboratory equipment. These features are intended to facilitate use in biomedical and clinical research settings.

The main finding was that whole-blood-derived EVs contained coordinated platelet- and mitochondria-associated protein and lipid signatures that were not detected in corresponding plasma-derived EV fractions. Whole-blood EV analysis therefore captures complementary biological information that is lost when only plasma or serum is examined. Relying solely on plasma or serum can overlook molecular signals relevant to disease mechanisms and biomarker discovery.

The work, entitled “Optimized enrichment of circulating extracellular vesicles from whole blood samples using PROSPR,” was published in Extracellular Vesicles and Circulating Nucleic Acids on July 7, 2026. By enabling the analysis of previously underused archived whole-blood samples, PROSPR provides a practical strategy to unlock valuable national and international biobank collections. This approach may support deeper investigation of disease mechanisms and expand opportunities for discovering circulating biomarkers for early diagnosis, prognosis, and disease monitoring.

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