Programmable DNA-responsive microchip for the capture and release of circulating tumor cells by nucleic acid hybridization

The detection and analysis of circulating tumor cells (CTCs) from patients′ blood is important to assess tumor status; however, it remains a challenge. In the present study, we developed a programmable DNA-responsive microchip for the highly efficient capture and nondestructive release of CTCs via nucleic acid hybridization. Transparent and patternable substrates with hierarchical architectures were integrated into the microchip with herringbone grooves, resulting in greatly enhanced cell-surface interaction via herringbone micromixers, more binding sites, and better matched topographical interactions. In combination with a high-affinity aptamer, target cancer cells were specifically and efficiently captured on the chip. Captured cancer cells were gently released from the chip under physiological conditions using toehold-mediated strand displacement, without any destructive factors for cells or substrates. More importantly, aptamer-containing DNA sequences on the surface of the retrieved cancer cells could be further amplified by polymerase chain reaction (PCR), facilitating the detection of cell surface biomarkers and characterization of the CTCs. Furthermore, this system was extensively applied to the capture and release of CTCs from patients′ blood samples, demonstrating a promising high-performance platform for CTC enrichment, release, and characterization.