High‐Density Arrangement of Biomimetic Plasmonic Nanoprobes Guided by DNA Nanoroller based Cleaving‐Rolling Process for SERS Sensing Analysis

Abstract DNA walker nanomachines are in fast development for biosensing, medical diagnostics, and food safety monitoring. For practical application, the issues of slow dynamics and low operational efficiency hinder its widespread application. Inspired by the high efficiency of agricultural cooperative machinery, a unique cleaving‐rolling‐assembly integrated nanodevice (CRAIN) is constructed for the high‐performance detection of various biomolecules. In the design, DNA nanotubes are introduced as building loaders to engineer polyoriented walking DNA nanorollers with blocked DNAzyme‐based walking strands and thus to increase the reaction direction and local concentration. Through target‐specific recognition, the activated nanorollers can autonomously and progressively cleave and roll along directional hairpin tracks on a gold substrate, significantly accelerating the reaction rate. Moreover, using nucleic acid‐encoded urchin‐shaped multispike gold‐silver composite nanospheres (nMGSs) as SERS‐enhanced probes, the engineered assembly of nMGSs probes induced by the cleaving‐rolling process promotes the formation of high‐density hotspot domains, further improving the detection sensitivity. With rational design, the CRAIN system can be extended to perform highly sensitive analyses of various analytes, such as microRNA‐21, butyrylcholinesterase activity and organophosphorus pesticides. This integrated assembly strategy can provide new perspectives for clinical diagnosis, biomedical engineering, and environmental science.