Antibody-free Isolation and Regulation of Adherent Cancer Cells via Hybrid Branched Microtube-sandwiched Hydrodynamic System

Detection of circulating tumor cells (CTCs) has achieved promising progress for early diagnosis and diseases analysis. Microfluidic chips techniques have recently prompted technologies of CTCs sorting and analysis, yet seldom microfluidic chips for CTCs enrichment via antibody-free capturing could provide in situ regulation of both extracellular and intracellular activities, which are advantageous for cell-based pharmaceutical therapeutics and screening. Herein, we have demonstrated a hybrid TiO2/ZnO branched microtube arrays (HBMTA)-sandwiched hydrodynamic device that integrated multiple functions of selective enrichment of adherent tumor cells in an antibody-free manner, and in situ delivery to the extracellular and intracellular spaces of the enriched tumor cells. More than 90% cancer cells were enriched on the device due to their adhesion preferences with the nano-branches of HBMTA, while more than 91% blood cells were eliminated from the device by constant hydrodynamic shearing fluid. For in situ regulation, temporally and spatially controlled extracellular delivery to the enriched tumor cells could be precisely achieved through the hollow structures of the HBMTA. In addition, reagents (e.g. propidium iodide) could be delivery of into the intracellular spaces enriched tumor cells by coupling electric field to nondestructively perforate cell membrane. Our study not only offers a promising and facile strategy for antibody-free isolation of tumor cells, but also provides unique opportunities to facilitate cancer research including anti-tumor drug screening and personalized therapeutics.