We report a contraction-expansion array (CEA) microchannel device that performs label-free high-throughput separation of cancer cells from whole blood at low Reynolds number (Re). The CEA microfluidic device utilizes hydrodynamic field effect for cancer cell separation, two kinds of inertial effects: (1) inertial lift force and (2) Dean flow, which results in label-free size-based separation with high throughput. To avoid cell damages potentially caused by high shear stress in conventional inertial separation techniques, the CEA microfluidic device isolates the cells with low operational Re, maintaining high-throughput separation, using nondiluted whole blood samples (hematocrit ~45%). We characterized inertial particle migration and investigated the migration of blood cells and various cancer cells (MCF-7, SK-BR-3, and HCC70) in the CEA microchannel. The separation of cancer cells from whole blood was demonstrated with a cancer cell recovery rate of 99.1%, a blood cell rejection ratio of 88.9%, and a throughput of 1.1 × 10(8) cells/min. In addition, the blood cell rejection ratio was further improved to 97.3% by a two-step filtration process with two devices connected in series.

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Continuous inertial blood plasma separation is demonstrated in a contraction–expansion array microchannel with a low aspect ratio (AR). The separation cutoff value of the particle size can be controlled by modulation of the force balance between inertial lift and Dean drag forces. The modulation is achieved by changing the channel AR at contraction region, which causes the change in magnitudes of the inertial lift forces on the particles. The presented blood plasma separator provides a level of yield and throughput of 62.2% and 1.2 ml/h(∼1.0×108 cells/min), respectively.

We report a contraction-expansion array (CEA) microchannel that allows three-dimensional hydrodynamic focusing with a single sheath flow in a single-layer device. The CEA microchannel exploits centrifugal forces acting on fluids travelling along the contraction and expansion regions of the microchannel. Around an entrance of the contraction region, the centrifugal forces induce a secondary flow field where two counter-rotating vortices enable to envelop a sample flow with a sheath flow in three dimensions. We herein describe an underlying principle and a design of the CEA microchannel and demonstrate complete sheathing of a sample fluid (water and human red blood cells) in three dimensions. The focusing characteristics of the CEA microchannel are investigated in terms of the number of the rectangular structures, flow rate, and flow ratio between sample and sheath flows. This microfluidic channel for three-dimensional hydrodynamic focusing is easy to fabricate in a single-layer fabrication process and simple to operate with a single sheath flow.

Three-dimensional lamination mixing is demonstrated in a simple and easily fabricated contraction-expansion array microchannel. The abrupt change of the cross-sectional area of the channel curves fluid streams and accelerates the flow velocity especially at the entrance of the contraction region. Centrifugal effects at that region result in Dean vortices that continuously split and redirect fluid streams, thereby enabling appreciable mixing. The presented mixer provides a level of 90% mixing in the relatively large range of Reynolds number from 4.3 to 28.6 by employing the channel with 30 contraction-expansion units.

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This paper demonstrates an inertia-activated cell sorting method to separate cells based on their surface protein expression by using inertial microfluidics.

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