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

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 (102 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.