High-throughput Rare Cell Detection and Separation Using Inertial Microfluidics

Rapid and accurate classification and purification of cell types within a heterogeneous suspension and precise manipulation of bio-particle positions in confined flow are challenging but important tasks for critical applications in biological research and medicine. This study focuses on development and evaluation of microfluidic devices for high-throughput diagnostic applications, such as cost-effective hematology and rare cell detection and enrichment. The microfluidic devices utilize inertial migration phenomena, which can focus and order particles and cells to geometrically-determined equilibrium positions in flow continuously without external forces (e.g. optical, electrical and magnetic), in order to separate target cells based on intrinsic properties (e.g. size and deformability). Behavior of numerous cell types, including blood cells, healthy tissue cells, various carcinoma cells (both benign and invasive), sarcoma cells, and mural progenitor cells from the tissue digests was tested based on the single-cell size and deformability, the flow rate, and the channel geometry. It was found that there exist optimum ranges of flow rates to manipulate living deformable cells for different applications (e.g., cell separation or uniform positioning). It was also investigated how deformability, shape, and asymmetry affect the behavior of particles flowing in the inertial microfluidics. The current study has successfully demonstrated the feasibility to precisely manipulate the position of living cells as well as microparticles in a flow using inertial microfluidics towards high-throughput label-free rare target cell classification and isolation.