Selective isolation of specific cell subpopulations from highly heterogeneous biological samples is an essential process in various biological studies and clinical applications. The ability to isolate rare cell populations, for example circulating tumor cells, provides unprecedented capabilities for the study of disease progression and better disease assessment. Currently, sorting and isolation of rare cell populations is typically performed using fluorescence-activated cell sorting (FACS) system, a technology developed nearly 60 years ago. These FACS systems are however complex, bulky, and expensive, require highly trained personnel for operation, and may produce bio-hazardous aerosols in open environments.

Microfluidics studies the unique behavior and interactions of fluids and particles at the micrometer length scale, typically in confined microscale channels. Microfluidic technology capable of precise cell manipulation thus has great potential to reinvent the next-generation cell sorting technology. We are currently developing two microfluidic cell sorting technologies including high-throughput hydrodynamic cell sorting and high-accuracy acoustic cell sorting. Hydrodynamic cell sorting is using an interesting inertial particle focusing behavior in an intermediate Reynolds number regime (~100 > Re > ~1). We have designed and fabricated a new type of hydrodynamic sorting device with a series of reverse wavy channel structures. These repeated wavy channels produce periodically reversed Dean secondary flow perpendicular to the main flow direction. The hydrodynamic inertial lift force and the Dean drag force scale with the particle size very distinctively, which leads to distinct equilibrium positions of differently sized particles. We have demonstrated the use of this new hydrodynamic sorting device to isolate cancer cells from blood cells without the use of sheath flows. Acoustic cell sorting is developed based on the study of interactions between high-frequency sound waves and microscale particles. In particular, I will discuss a unique design of a focused interdigital transducer (FIDT) structure, which is able to generate a highly localized acoustic field on the order of 25 µm wide. This highly focused acoustic beam has an effective manipulation area size that is comparable to individual micron-sized particles. We have demonstrated the use of this highly localized acoustic field for fluorescence-activated single cell level sorting with sub-millisecond pulses. By combining the two microfluidic cell sorting technologies, we have demonstrated the capability of enriching target cells by 1,000 to 10,000 times, providing a new solution of rare cell isolation.