Acoustofluidic Plasmapheresis System Designed for Ultralow Blood Volume Applications

We present an integrated acoustofluidic plasmapheresis system designed for ultralow blood volume applications, such as neonatal care, enabling in-line sampling and plasma separation from whole blood. The system combines a two-stage acoustophoresis chip with microperistaltic pumps and PDMS-based flow pulsation dampeners to ensure continuous, stable operation. The input whole blood is acoustically separated into a cell-free plasma fraction and a returnable cell fraction, enabling closed-loop operation for neonates who have a circulating blood volume as low as 50 mL. The system achieves a plasma generation rate of 27.5 μL/min with ∼100% cell removal, outperforming previous microfluidic plasma separation approaches in terms of purity, throughput, and minimal sample volume. Plasma quality was validated by quantifying hemolysis and residual cellular content, while system robustness was demonstrated across hematocrit levels up to 50%, which is close to the average upper hematocrit value in neonates. Compared to previous microfluidic techniques, our system achieves the fastest generation of clinical quality undiluted plasma with the lowest required blood volume, making it highly suitable for point-of-care integration in neonatal intensive care units.