Microfluidic flow fractionation for isolation of circulating tumor cells

Circulating tumor cells (CTCs) are highly correlated with the invasive behavior of cancer, so their isolations and quantifications are important for biomedical applications such as cancer prognosis and measuring the responses to drug treatments. In this chapter, we present the development of various microfluidic devices for the separation of CTCs from blood cells based on the physical properties of cells and microfluidic flow fractionation. For a continuous size-based separation of CTCs, firstly we designed a new microfluidic method, multi-orifice flow fractionation (MOFF), which utilizes inertial lift force and momentum-change-induced inertial force generated in a series of contraction/expansion microchannels. Secondly, we fabricated a microfluidic channel for multi-stage multi-orifice flow fractionation (MS-MOFF), which is made by combining three multi-orifice segments, and consists of 3 inlets, 3 filters, 3 multi-orifice segments and 5 outlets. Thirdly, we combined multi-orifice flow fractionation (MOFF) and dielectrophoretic (DEP) cell separation technique. Hydrodynamic separation such as flow fractionation takes advantage of the massive and high-throughput filtration of blood cells as it can accommodate a very high flow rate. We will describe advantages and disadvantages of our various MOFF systems and suggest that our systems will be useful for separation and detection of CTCs from blood cells for biomedical applications.