Cell-Mimetic Antifouling Poly(ethylene glycol) Interface Enables Selective Capture and Viable Release of Circulating Tumor Cells

Circulating tumor cells (CTCs) hold great promise as biomarkers for cancer diagnosis, metastasis assessment, and therapeutic monitoring. However, their extremely low abundance and interference from complex blood components make their efficient and specific isolation highly challenging. Herein, we developed a reduction-responsive, antifouling, and cell-mimicking silica-patterned platform functionalized with bispecific antibodies (BsAbs, anti-PEG scFv, and anti-HER2 scFv) for selective CTC capture. The PEG-modified surface effectively suppressed nonspecific adhesion of immune cells, while the BsAbs and rough substrate topology synergistically enhanced the capture efficiency and specificity toward HER2-overexpressing tumor cells (SKBR3). Notably, the captured cells could be gently released upon treatment with glutathione, preserving their viability for subsequent culture and analysis. This study provides a robust and controllable strategy for highly-specificity CTC isolation, offering a promising tool for liquid biopsy-based cancer diagnostics.