A versatile biointerface with multiply flexible spatial molecular layers for improving tumor cell isolation and detection

Circulating tumor cells (CTCs) serve as critical biomarkers in liquid biopsy, creating a demand for materials capable of their specific capture. Conventional rigid micro/nanostructures are often hindered by a dimensional mismatch with cells and limited deformability, resulting in inefficient use of capture sites. In this study, we constructed a versatile biointerface with multiply flexible molecular layers (M-FML) to overcome these limitations. The M-FML was fabricated on a silicon substrate by alternately polymerizing poly-γ-glutamic acid and poly-ε-lysine. With an average height of approximately 20.20 ± 1.21 μm, this layer mimics the topological features of the extracellular matrix. The flexible and dynamic macromolecular chains within the M-FML greatly improve both the contact probability and spatial compatibility with recognition sites on cell surfaces. The substrate demonstrated strong capture performance for SK-BR-3 and MDA-MB-231 cells, maintaining efficiencies of about 36.67% and 40%, respectively, even at very low cell densities in environments simulating whole blood. Furthermore, the surface showed excellent resistance to the non-specific adhesion of fibrinogen, platelets, and other blood components. This work presents a flexible interfacial strategy for the efficient and specific enrichment of CTCs from complex biological samples.