A circular gradient-width crossflow microfluidic platform for high-efficiency blood plasma separation

Abstract

Separation and collection of blood plasma are required steps for broad ranges of clinical diagnostic assays. Here, we introduce a continuous-flow blood plasma separation microfluidic device based on size exclusion cell separation in crossflow microchannels. A gradient-width crossflow microchannel structure is utilized to minimize blood cell leakage into the plasma collection channel while maximizing the flow rate for higher throughput. Additionally, the crossflow channels are placed at the corner of the blood channel to enhance Fahraeus effects, resulting in reduction of the concentration of blood cells around the entrance of the crossflow channels. Combined with a circular geometry that minimizes the footprint of the device for point-of-care diagnosis applications, the developed device significantly improves the performance of blood plasma separation in terms of separation efficiency, degree of hemolysis, and microchannel clogging by blood cells. At a relatively high flow rate of 2000 µl/h for a passive blood separation device, a plasma extraction ratio of 22% and red blood cell separation efficiency of 97% could be achieved using undiluted whole human blood, where such separation efficiency is about 28% higher compared with that of a conventional crossflow design. The effect of channel height and flow rate on the degree of hemolysis was also investigated, where the optimized device could achieve very little hemolysis (0.01–0.5%), demonstrating that the device can produce high-quality blood plasma. Integration of this high-performance, compact, and passive blood plasma separation microdevice with on-chip blood biomarker sensing elements can create a point-of-care diagnosis system with reduced cost, test time, and sample/reagent volume.