Constriction-induced capture of rare cells using interdigitated microchannels with bidirectionally perforated thin honeycomb films

The efficient capture and detection of rare target cell populations from complex biological fluids holds great promise for next-generation diagnostics, therapeutics, and bioprocess engineering. Here, we present a versatile microfluidic platform incorporating a thin honeycomb film (HCF) with laterally and vertically perforated micropores. The HCF is sandwiched between and supported by a glass slide and a PDMS substrate with interdigitated microchannels, enabling stable, bidirectional transmembrane flows even under high flow rate conditions. Large and/or less deformable cells were selectively trapped on the micropores of the HCF at the bottom of the interdigitated channels due to physical constriction. Using an HCF with 2.7 μm pores, we achieved highly efficient separation of white blood cells (WBCs) from diluted human blood, with minimal red blood cell contamination. Furthermore, employing a 10.4 μm pore HCF, we captured model circulating tumor cells (CTCs) with over 90 % efficiency at a flow rate of 500 μL/min, while suppressing nonspecific adhesion of other blood cells. The high capture efficiency, simple fabrication process, and tunable selectivity of the presented device offer significant advantages for rare cell-targeted liquid biopsy and therapeutics.