DNA-mediated precise regulation of SERS hotspots for biosensing and bioimaging

Surface-enhanced Raman scattering (SERS) is a powerful analytical technique, where the creation of "hotspots" holds the key to unlocking sensitive, reproducible and reliable performance. DNA nanostructures, known for their unique predictability and exceptional programmability, have emerged as promising tools for the controllable assembly and precise regulation of SERS hotspots. In recent years, the application of DNA nanotechnology in the regulation of SERS hotspots has emerged as a research focus, but a comprehensive summary of this field is still lacking. This review begins by elucidating the mechanisms of localized surface plasmon resonance (LSPR) coupling and SERS enhancement, providing a theoretical foundation for the design principles and assembly strategies for SERS hotspots. Following this, general approaches for assembling static SERS hotspots using DNA structures of different dimensions as linkers or templates are explored. Subsequently, we delve into dynamic regulation strategies for SERS hotspots mediated by DNA structures, focusing on structural reconfiguration driven by DNA hybridization, toehold-mediated strand displacement (TMSD), and enzyme-catalyzed DNA allostery, and then summarize recent examples of DNA-mediated hotspot regulation in biosensing and bioimaging applications. Finally, we discuss future perspectives associated with the DNA-mediated precise regulation of SERS hotspots, underscoring the imperative for enhanced scalability, uniformity, and integration to pave the way for real-world applications.