DNA Nanotechnology in Surface‐Enhanced Raman Scattering: Precision Engineering, Dynamic Biosensing, and Future Horizons

DNA nanotechnology has emerged as a transformative tool in surface‐enhanced Raman scattering (SERS), enabling unprecedented precision in plasmonic hotspot engineering, dynamic signal amplification, and multiplexed biomarker detection. By leveraging the programmable self‐assembly of nucleic acids, researchers have developed composite SERS substrates, enzyme‐free amplification strategies, and aptamer‐mediated recognition systems, achieving attomolar sensitivity for targets ranging from cancer exosomes to heavy metals. Framework nucleic acids further enhance spatial resolution, while DNA nanomachines and hydrogels introduce stimuli‐responsive capabilities for real‐time monitoring. However, challenges persist in stability, scalability, and spectral multiplexing, necessitating innovations in nuclease‐resistant designs, cost‐effective fabrication, and machine learning‐assisted data analysis. Future directions include CRISPR‐SERS integration, field‐portable devices, and quantum‐plasmonic hybrids. By bridging molecular programmability with plasmonics, DNA nanotechnology promises to revolutionize SERS applications in precision diagnostics, environmental surveillance, and single‐molecule analysis.