Nanotentacle-Armed Flexible Affinity Interface Enables Streamlined Capture, Labeling, and Release of Circulating Tumor Cells

Liquid biopsy based on circulating tumor cells (CTCs) is regarded as a promising approach for cancer diagnosis, therapeutic evaluation, and metastasis monitoring. However, conventional CTC identification processes after CTC isolation are labor-intensive and can lead to CTC inactivation. Here, we present a nanotentacle-armed flexible affinity interface (NataFace) designed for the capture, release, and labeling of CTCs. Engineered from M13 bacteriophages and boronate affinity chemistry, NataFace integrates flexibility-enhanced and local multivalent interactions to achieve superior CTC capture affinity and selectivity. Using a programmable DNA-based "light-up" strategy, captured CTCs are self-labeled, enabling precise identification without the need for tedious and destructive immunostaining. Additionally, mild acidic fructose treatment allows the release of viable CTCs, preserving their phenotypic integrity for downstream applications. Importantly, NataFace is regenerable, enabling recharging with aptamers targeting different biomarkers for adaptable cell isolation. Clinical validation using cancer patient blood samples demonstrated high sensitivity, specificity, and consistency with standard immunofluorescence methods. Beyond CTC isolation, NataFace's multifunctional, renewable design positions it as a versatile platform with potential applications in drug delivery, immunosorbent assays, and hemopurification. This offers a transformative approach to liquid biopsy and personalized medicine.