Continuous High-Throughput Plasma Separation for Blood Biomarker Sensing Using a Hydrodynamic Microfluidic Device.

Abstract

Continuous, cost-effective, high-throughput with admissible yield and purity of blood plasma separation is widely needed for biomarker detection in the clinic. The existing gold standard technique (centrifugation) and microfluidic technologies fall short of meeting these criteria. In this study, a microfluidic device design is demonstrated based on passive hydrodynamic principles to achieve admissible yield and purity plasma samples. Through computational and experimental assessments, it is shown that side channels with varying lengths are required to improve the plasma extraction rate. The optimized side channels in this device design use the formed cell-free layer regions in the expanded areas to extract plasma consistently and efficiently. These Hydrodynamic Continuous, High-Throughput Plasma Separator (HCHPS) microfluidic devices achieve a purity in the range of 47% to 64% with whole blood and maintaining a yield of 10% to 18%, with half hemolysis compared to gold standard centrifugation. These devices also separate the plasma from diluted blood with a purity in the range of 62% to 97% with a similar yield range. Additionally, whole human blood spiked with lactate was processed through the HCHPS device, and the separated plasma is collected and analyzed using two biosensing approaches, a bead-based fluorescence, and an electrochemical aptamer biosensing, confirming the quality of plasma for downstream biomarker detection.