Rare Blood Cell Separation on a Microfluidic Platform: A Case Study of Circulating Tumor Cells

Microfluidic devices can exploit unique aspects of blood rheology (e.g., the Fahreaus effect, plasma skimming and nucleated cell margination) to separate nucleated cells (NC) from whole blood. To optimize cell separation in a microfluidic platform, we created polydimethylsiloxane (PDMS) rectangular microchannels of various geometries and topologies and analyzed the auto‐segregation (margination) of nucleated cells (NCs). We found, similar to previous studies in tubes of circular cross sections – and in real blood vessels – that NC margination in rectangular microchannel geometries depends on flow, hematocrit and red blood cell (RBC) aggregation. It also is exaggerated in abrupt and repeated expansions. Based on the resulting design constraints, we have prepared devices that reliably extract marginated NCs with separation efficiency greater than 98%, resulting in a 50‐fold increase in NC‐to‐RBC ratio. We have further extended the design to improve the immuno‐capture of circulating tumor cells (CTC) from whole blood. This platform can easily be integrated with lab‐on‐a‐chip modules that perform PCR, nucleic acid isolation and detection, allowing a complete rare cell analysis on chip.