Nano-Interstice Driven Powerless Blood Plasma Extraction in a Membrane Filter Integrated Microfluidic Device

Abstract

Blood plasma is a source of biomarkers in blood and a simple, fast, and easy extraction method is highly required for point-of-care testing (POCT) applications. This paper proposes a membrane filter integrated microfluidic device to extract blood plasma from whole blood, without any external instrumentation. A commercially available membrane filter was integrated with a newly designed dual-cover microfluidic device to avoid leakage of the extracted plasma and remaining blood cells. Nano-interstices installed on both sides of the microfluidic channels actively draw the extracted plasma from the membrane. The developed device successfully supplied 20 μL of extracted plasma with a high extraction yield (~45%) in 16 min.

Keywords: blood plasma extraction; microfluidics; point-of-care testing.

Figure 1

Overall illustration of the plasma separation microfluidic device with the dual cover. (a) Fabrication process of the device and the result of fabrication. (b) Application of whole blood on the device and feature of the device. (c) Section AA’ represents the process of plasma flow by the nano-interstice (NI)-driven flow. (d) Section BB’ indicates the mechanical prevention of red blood cell leakage by the dual cover system. (e) Whole blood application to single- and dual-cover devices. The red arrowhead indicates blood leakage. Scale bar, 4 mm.

Figure 2

Evaluation of plasma separation performance of membrane filter according to the filter sizes and volume of whole blood. (a) Weight-based evaluation process using the absorbent pad. Blood plasma separation volume and yield of the membrane filter from 50 μL (b), 80 μL (c), and 100 μL (d) of whole blood (N = 8, error bars indicate standard deviation).

Figure 3

Plasma extraction in the dual cover microfluidic chip. (a) Images of plasma extraction in the chip depending on time. The red solid line and dotted line indicate the filter and whole blood insertion parts, respectively. The yellow solid line and dotted line represent acetone bonded edge and NI channel, respectively. Scale bars, 2 mm. (b) Graph of the volume of separated plasma into the microchannel.

Figure 4

Position of plasma extraction efficiency graph. The solid rectangle represents the developed system. P+: External Power Type, P−: Powerless Type.