Spatially Controlled DNA Frameworks for Sensitive Detection and Specific Isolation of Tumor Cells

High‐affinity, specific, and sensitive probes are crucial for the specific recognition and identification of tumor cells from complex matrices. Multivalent binding is a powerful strategy, but the irrational spatial distribution of the functional moieties may reduce the probe performance. Here, we constructed a Janus DNA triangular prism nanostructure (3Zy1‐JTP‐3) for sensitive detection and specific isolation of tumor cells. Benefiting from spatial features of the triangular prism, the fluorescence intensity induced by 3Zy1‐JTP‐3 was almost 4 times that of the monovalent structure. Moreover, the DNA triangular prisms were connected to form hand‐in‐hand multivalent DNA triangular prism structures (Zy1‐MTP), in which the fluorescence intensity and affinity were increased to 9‐fold and 10‐fold of 3Zy1‐JTP‐3, respectively. Furthermore, 3Zy1‐JTP‐3 and Zy1‐MTP were combined with magnetic beads, and the latter showed higher capture efficiency (> 90%) in whole blood. This work provides a new strategy for the efficient capture of rare cells in complex biological samples.