DNA‐Regulated Catalytic‐Plasmonic Colocalization Enables Synergistic Signal Amplification in SERS and Nanozyme‐Based Sensors

Abstract

ABSTRACT The critical need for accessible disease monitoring underscores the urgency of developing advanced point‐of‐care testing (POCT). We present a DNA‐regulated catalytic‐plasmonic colocalization‐based synergy coupling mechanism that resolved the spatiotemporal disjunction commonly present in conventional SERS‐catalysis systems through programmed spatial confinement. Rolling circle amplification‐derived DNA nanocages were employed as programmable spatial regulators to precisely position Au@Pt nanozymes within plasmonic hotspots via base pair encoded hybridization, thereby enforcing spatial and temporal consistency between catalytic generation of Raman‐active species and electromagnetic field enhancement. This strategy integrated coordinated interface, pore, and interlayer confinement, enabling cross‐scale signal amplification from molecular to microscale levels. As a result, it yielded exceptional SERS enhancement (an approximate 41‐fold versus controls), sensitivity (10 2 exosomes µL −1 ), and reproducibility (6.5% RSD). To translate this mechanism into practical application, a portable dual‐modal detection platform with potential point‐of‐care applicability was developed that preserved catalytic‐plasmonic colocalization during both colorimetric screening and SERS quantification. The device achieved radical miniaturization (95% volume, 91% weight reduction) and cost‐efficiency (90% reduction vs. commercial systems). By coupling programmable nanomaterial design with customizable device engineering, we established a robust paradigm for next‐generation POCT, providing a promising platform for biomedical detection, environmental surveillance, and food safety monitoring.