Enhanced stiffness-based sorting of cancer cells using a microfluidic with slanted zig-zag ridges and step-wise compression

The deformability of tumor cells provides information about the metastatic capabilities of cancer and the ability to sort tumor cells, especially circulating tumor cells (CTCs), based on the stiffness. CTCs of different stiffness can be sorted by hydrophoresis that utilizes slanted or herringbone uniform ridges. When CTCs are deformed by the ridges, a transverse force proportional to cell membrane stiffness is generated to enable crossflow migration. To accentuate this sorting mechanism and sensitivity, we proposed a new 3D microfluidic design that incorporates slanted zig-zag ridges and step-wise progressive compression that collectively increase the elastic forces and residence time. Numerical simulation was performed to determine the trajectories of cells with different stiffness and the optimal design parameters. Experimental validation will be performed using PC-3 cells treated with or without cytochalasin that chemically reduces cell stiffness while maintaining a similar diameter. Further comparisons will be done between the proposed new design with the conventional uniform ridges design. Additional modeling efforts on cell-compliant wall interaction will also be provided.