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

Circulating tumor cells (CTCs) enrichment by aptamers shows a number of advantages, but the issue of compromised binding affinities and stabilities in real samples hinders their wide applications. Inspired by the high efficiency of the prey mechanism of octopus, we engineered a deterministic lateral displacement (DLD) patterned microfluidic chip modified with interfaces mimicking the multivalent tentacles of octopus using aptamer‐functionalized nanospheres, called as aptamer‐tailed octopus‐chip (AP‐Octopus‐Chip) to enhance capture efficiency. The multivalent aptamer‐antigen binding improves 100 folds and the capture efficiency enhanced more than 300% compared with a monovalent aptamer modified chip. Moreover, the enriched cancer cells can be released via 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 AP‐Octopus‐Chip, we were able to find CTCs in 100% cancer samples (13 colorectal and 24 prostate cancer patients). Overall, this method brings a fresh approach to aptamer‐based clinical CTC analysis, pushing one step further towards practical use.

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