Bioinspired Engineering of a Multivalent Aptamer‐Functionalized Nanointerface to Enhance the Capture and Release of Circulating Tumor Cells

Circulating tumor cell (CTC)‐enrichment by using aptamers has a number of advantages, but the issue of compromised binding affinities and stabilities in real samples hinders its wide applications. Inspired by the high efficiency of the prey mechanism of the octopus, we engineered a deterministic lateral displacement (DLD)‐patterned microfluidic chip modified with multivalent aptamer‐functionalized nanospheres (AP‐Octopus‐Chip) to enhance capture efficiency. The multivalent aptamer–antigen binding efficiency improves 100‐fold and the capture efficiency is enhanced more than 300 % compared with a monovalent aptamer‐modified chip. Moreover, the captured cancer cells can be released through a thiol exchange reaction with up to 80 % efficiency and 96 % viability, which is fully compatible with downstream mutation detection and CTC culture. Using the chip, we were able to find CTCs in all cancer samples analyzed. Octopus chip cell capture: Inspired by the high efficiency of the prey mechanism of the octopus, an aptamer‐tailed octopus chip (AP‐Octopus‐Chip) for CTC enrichment was developed. The design of the chip and the high binding affinity of the multivalent structures against the target cells significantly improved the CTC capture efficiency and enrichment. The enriched cancer cells can be released through a thiol exchange reaction, which is fully compatible with downstream mutation detection and CTC culture.