Nanoassembled SERS Sensing for Complex Biological Systems: From Hotspot Engineering to Interface Regulation

作者：Haochen Ye, Weidong Zhao, Tie Wang · 发表于：Accounts of Chemical Research · 年份：2026 · DOI：10.1021/acs.accounts.6c00236 · 被引用次数：1 · 研究领域：Gold and Silver Nanoparticles Synthesis and Applications、Innovative Microfluidic and Catalytic Techniques Innovation、Spectroscopy Techniques in Biomedical and Chemical Research

ConspectusSurface-enhanced Raman scattering (SERS) has evolved over the past five decades into a powerful vibrational spectroscopic technique capable of single-molecule sensitivity. Despite significant advances in the rational design and fabrication of SERS substrates with abundant hotspots, SERS still faces formidable challenges in transitioning from laboratory demonstrations to reliable analysis in complex biological environments. In practical sensing scenarios, the achievable enhancement factor is rarely the decisive parameter. Instead, the dominant bottleneck lies at the interface, where analyte transport and capture, as well as signal stability, are governed by dynamic mass transfer and matrix interference. A predictive understanding and rational regulation of analyte-hotspot interactions are therefore urgently needed.In this Account, we present a conceptual shift in SERS substrate design: from passive hotspot engineering to active interface regulation. Rather than focusing solely on maximizing local electromagnetic fields, we integrate hotspot construction with dynamic control over interfacial interactions, establishing a unified framework for SERS sensing in gas, liquid, and solid-state biological systems. We first summarize our efforts in constructing highly ordered and reproducible plasmonic assemblies as a structural foundation for reliable sensing. Traditional hotspot engineering strategies often rely on sophisticated top-down nanofabrication techniques or poorly c...