Centrifuge-free separation of plasma from milliliters of whole blood for point-of-care diagnostics.

Performing efficient plasma separation from whole blood, a vital sample matrix for diagnostics, in point-of-care settings remains challenging, particularly for sensitive assays that require larger volumes than can be obtained from a finger prick. Centrifugation, the gold standard for plasma separation, relies on bulky equipment and trained personnel, making it difficult to implement in decentralized settings. Current point-of-care (POC) plasma separation methods are limited to microliter blood volumes, which are insufficient for high-sensitivity clinical applications; these tools also require manual operation and yield limited plasma volumes. Here, we present PlasmaLIFT (Large-volume Immunodepletion and Filtration Tool), an automated and compact device that uniquely combines two plasma separation strategies-immunomagnetic red blood cell depletion that enables downstream filtration without clogging, and a dual membrane size-exclusion filtration recently developed that removes remaining cells-to enable rapid, efficient plasma separation from 5 mL of whole blood within 10 minutes. PlasmaLIFT removes over 99.9% of cellular components without needing significant dilution or causing hemolysis, achieves a high plasma recovery efficiency of 80% at physiological hematocrit levels, and produces plasma containing clinically relevant biomarkers-demonstrated here for proteins, metabolites, lipids, nucleic acids, and viruses-at levels comparable to those obtained with centrifugation. This scalable, automated, centrifuge-free approach facilitates high-volume plasma separation in decentralized settings, potentially expanding access to sensitive blood-based diagnostic testing; future work to reduce the cost of magnetic beads at scale will expand access even further to low-resource settings.