Hierarchically Engineered Phage-Activated Click Interface for Ultra-Efficient Cell Capture

This is the authors' abstract. We don't add key points for this paper.

Efficient cell adhesion under flow is vital in biological processes and artificial capture systems governed by the frequency of cell-surface encounters and the probability of successful binding. While previous efforts mainly focused on enhancing these factors at the molecular level within two-dimensional interfaces, strategies that simultaneously boost both aspects across the multiscale spatial level remain largely unexplored. In this study, we developed a multiscale hierarchically engineered cell capture interface, PACE-Chip, which integrates click chemistry at the molecular level, nanofiber-like M13 phage scaffolds at the interfacial microscale, and herringbone structures at the device macroscale, achieving synergistic enhancement of both cell binding kinetics or affinity. The PACE-Chip exhibited 294% higher binding strength and 181-fold faster binding kinetics compared to its two-dimensional counterpart, enabling the highly efficient isolation of target cells from complex blood matrices down to the single-cell level. Further analysis revealed that excessive phage length compromises performance due to entropic and structural penalties, highlighting the multiscale trade-off between multivalency and conformational stability.