Fold-crease induced paper wicking enhancement enabling rapid and high-yield plasma separation

Plasma separation from whole blood is a critical/first step in blood sample preparation and various clinical diagnostic applications. Traditional centrifugation methods often require complex equipment, skilled operators, and large volume sample (∼mL), which limits their use in point-of-care (POC) testing and resource-limited areas. Paper-based microfluidic devices (μPADs) present a viable alternative for POC plasma separation, while their plasma yield is often constrained, due to the blockage of red blood cells (RBCs) and the restricted liquid wicking capacity of papers.

Here, we proposed the folded-paper plasma separation device (FPSD), a compact platform that integrates antibody-induced RBC aggregation, crease-enhanced plasma wicking, and gravity-amplified differences in plasma and RBC wicking distance, enabling rapid and efficient plasma separation from whole blood. We successfully achieved high-yield (∼45.56%) plasma separation using FPSD within just 2 min. Moreover, FPSD enabled ultra-high plasma purity (∼99.9%) from ∼20 μL whole blood sample.

Finally, we integrated FPSDs with colorimetric analysis to enable the accurate detection of blood glucose and cholesterol from the separated plasma. FPSDs, origami-inspired plasma separation devices, leverage crease-enhanced wicking capacity to improve fluid transport, offering easy handling, low cost, and new opportunities for paper-based microfluidic chips and blood-based POC diagnostics.