Vortex chip incorporating an orthogonal turn for size-based isolation of circulating cells

Highlights: • Orthogonal vortex chip for label-free size-specific cell and particle isolation. • Orthogonal configuration enhances formation of vortices and engenders turn-effect. • Inertial forces involved in turn-effect result in differential ejection of particles. • Vortex-trapping is accomplished at lower flow velocities which aids cell viability. • Results affirm applicability of device in gentle isolation of circulating tumor cells. Size-based label-free separation of rare cells such as CTCs is attractive due to its wider applicability, simpler sample preparation, faster turnaround and better efficiency. Amongst such methods, vortex-trapping based techniques offer high throughput but operate at high flow velocities where the resulting hydrodynamic shear stress is likely to damage cells and compromise their viability for subsequent assays. We present here an orthogonal vortex chip which can carry out size-differentiated trapping at significantly lower (38% of previously reported) velocities. Composed of entry-exit channels that couple orthogonally to a trapping chamber, fluid flow in such configuration results in formation of a vortex which selectively traps larger particles above a critical velocity while smaller particles get ejected with the flow. We call this phenomenon the turn-effect. Critical velocities and optimal architectures for trapping of cells and particles of different sizes are characterized. We explain how shear-gradient lift, centrifugal and Dean flow drag forces contribute to the turn-effect by pushing particles into specific vortex orbits in a size- and velocity-dependent fashion. Selective trapping of human breast cancer cells mixed with whole blood at low concentration is demonstrated. The device shows promising results for gentle isolation of rare cells from blood.