Flash: Dual-gradient filtering membranes enable ultra-fast plasma separation.

Background: Whole blood sample consists of red and white blood cells, platelets, nucleic acids, proteins, and other metabolites. However, the presence of blood cells will affect the monitoring of biomarker in plasma. To obtain plasma from microscale whole blood, plasma separation membranes are commonly used. However, obtaining high-purity plasma within a short time in point-of-care cases still remains a significant challenge. It is evident that achieving high yield/purity and high recovery rate of markers plasma separation from microliters of whole blood in an extremely short time is crucial for the point-of-care (POC) testing.

Results: Here, we propose dual-gradient (structural\wetting gradient) plasma separation membranes (DG-PSMs) to effectively address the above issue. Specifically, the upper layer of DG-PSM pre-treated by blood-typing antibody exhibits hydrophobicity, which can promote red blood cell (RBC) agglutination reaction. In addition, the wetting gradient can generate wetting gradient force, which also facilitates the rapid transport of plasma. As a result, the DG-PSM can extract extremely pure plasma (∼99.99 %) from ∼15 μL whole blood. More importantly, the plasma separation costs only 15 s, far less than that of other traditional plasma separation membranes (e.g., 5-10 min). The flash separation process reduces the possibility of entanglement/absorption of protein by paper fibers, achieving an ultra-high protein recovery rate (∼98.88 %). In addition, the DG-PSM is comparable to centrifugation in avoiding hemolysis of RBCs.

Significance: More importantly, the plasma separated by DG-PSM was tested for blood glucose detection by integrating microfluidic paper-based analytical devices (μPADs) and colorimetric assays, which achieved rapid blood glucose detection (∼20 s). The DG-PSM promotes the realization of plasma separation and detection on lab-on-a-chip. We believe DG-PSM can be integrated into more detection devices to benefit mankind in remote areas and developing countries.