High-Throughput, Label-Free Isolation of White Blood Cells from Whole Blood Using Parallel Spiral Microchannels with U-Shaped Cross-Section

Abstract

Rapid isolation of white blood cells (WBCs) from whole blood is an essential part of any WBC examination platform. However, most conventional cell separation techniques are labor-intensive and low throughput, require large volumes of samples, need extensive cell manipulation, and have low purity. To address these challenges, we report the design and fabrication of a passive, label-free microfluidic device with a unique U-shaped cross-section to separate WBCs from whole blood using hydrodynamic forces that exist in a microchannel with curvilinear geometry. It is shown that the spiral microchannel with a U-shaped cross-section concentrates larger blood cells (e.g., WBCs) in the inner cross-section of the microchannel by moving smaller blood cells (e.g., RBCs and platelets) to the outer microchannel section and preventing them from returning to the inner microchannel section. Therefore, it overcomes the major limitation of a rectangular cross-section where secondary Dean vortices constantly enforce particles throughout the entire cross-section and decrease its isolation efficiency. Under optimal settings, we managed to isolate more than 95% of WBCs from whole blood under high-throughput (6 mL/min), high-purity (88%), and high-capacity (360 mL of sample in 1 h) conditions. High efficiency, fast processing time, and non-invasive WBC isolation from large blood samples without centrifugation, RBC lysis, cell biomarkers, and chemical pre-treatments make this method an ideal choice for downstream cell study platforms.

A dielectrophoresis-based microfluidic system having double-sided optimized 3D electrodes for label-free cancer cell separation with preserving cell viability

“…This paper investigates the performance of a proposed DEP device for three different configurations of 3D electrodes to separate MDA-MB-231 cancer cells from the different subtypes of WBCs with a cell viability approach. It should be noted that WBCs and CTCs are slightly larger than other blood components, so before separating WBCs from CTCs in the proposed system, they can be separated from other blood components using these two methods: (1) conventional cell sorting techniques such as centrifugation with density gradient, and (2) cell sorting based on microfluidic systems using deterministic lateral displacement (DLD) 36 , pinch flow fractionation (PFF) 37 , hydrodynamic filtration 38 , and inertial migration 39 mechanisms. In this section, various parameters such as cell trajectory, the electric field in the microchannel, DEP force applied to cells, and Joule heating are surveyed.…”

Signal-Based Methods in Dielectrophoresis for Cell and Particle Separation

“…Microfluidics enables the miniaturization of these analytical devices by controlling the fluid flow along a microchannel. Moreover, it is widely used in particle manipulation processes, such as focusing, sorting, and trapping micro to nanoparticles [ 2 , 3 ]. These microfluidic platforms provide fast response time, portability, precise manipulation, low cost, and less sample volume consumption [ 4 ].…”

“…In contrast, an external field is used for sorting particles in an active sorting technique [ 2 , 3 , 4 ]. Dielectrophoresis (DEP), magnetic [ 3 , 4 , 5 , 6 ], optical [ 7 , 8 , 9 ], and acoustic [ 10 ] methods are some examples of active sorting techniques. Generally, active sorting methods result in higher efficiency and throughput than passive sorting ones.…”

Signal-Based Methods in Dielectrophoresis for Cell Separation

“…Microfluidics enables the miniaturization of these analytical devices by controlling the fluid flow along a microchannel. Also, it is widely used in particle manipulation processes, such as focusing, sorting, and trapping micro to nanoparticles [2,3]. These microfluidic platforms provide fast response time, portability, precise manipulation, low cost, and less sample volume consumption [4].…”

“…In contrast, an external field is used for sorting particles in an active sorting technique [2][3][4]. Dielectrophoresis (DEP), magnetic [3][4][5][6], optical [7][8][9], and acoustic [10] methods are some examples of active sorting techniques. Generally, active sorting methods result in higher efficiency and throughput than passive sorting ones.…”