Label-free isolation of rare tumor cells from untreated whole blood by interfacial viscoelastic microfluidics

Label-free, high-throughput, and efficient separation and enrichment of rare tumor cells, such as circulating tumor cells (CTCs), from untreated whole blood is a challenging task, owing to extremely rare events of CTCs and an enormous amount of blood cells. Current strategies for CTC separation always require pre-processing steps including lysis of blood or labeling of CTCs, leading to loss or damage of CTCs. Here, we report an interfacial viscoelastic microfluidic system for size-selective separation of tumor cells directly from whole blood, without the need of cell labeling and other treatments. The sharp flow interfaces between the sample flow and viscoelastic flow (0.05% PEO solutions) in the straight microchannel allow for the penetration of large tumor cells while blocking small blood cells, through exploiting the competition between the inertial lift forces and interfacial elastic lift forces. The microfluidic paradigm does not involve external force fields or complicated fabrication procedures, while achieving 95.1% separation efficiency and 77.5% recovery rate for isolating as few as 50 tumor cells in 1 mL whole blood. The viability of tumor cells after separation is ∼100%, and normal proliferation of separated tumor cells is observed. The interfacial viscoelastic microfluidics holds great promise to facilitate the fundamental and clinical studies of CTCs. Label-free, size-dependent, and high-throughput isolation of rare tumor cells from untreated whole blood is enabled by interfacial viscoelastic microfluidics.