Mismatch-Tuned Plasmonic Nanogap Networks on Block Copolymers for Ultrasensitive Nucleic Acid Quantification

Abstract In localized surface plasmon resonance (LSPR), rational nanogap engineering in metallic nanostructures enables strong plasmonic coupling and efficient confinement of incident electromagnetic fields, thereby significantly enhancing optical responses for biosensing applications. Traditional approaches to fabricating small gaps have relied on localizing dielectric spacers between gold nanoparticles (AuNPs). However, doing so has encountered challenges in producing high-density, clean gaps across large surface areas. Here, we demonstrate a straightforward, self-assembly-guided method for the consistent fabrication of topologically anchored AuNPs featuring sub-5 nm nanogaps, arranged on a nanostructured block copolymer template. The solution-based method enables time-dependent tuning toward high plasmonic coupling density, resulting in an extensive number of hotspots, with an equivalent sensing enhancement factor (ESEF) exceeding that of thermally annealed gold nanoisland chips by 1 × 105. Laser excitation of these densely packed AuNPs at their plasmonic resonance efficiently drives both nucleic acid hybridization and amplification-based cyclic fluorescence probe cleavage, enabling SARS-CoV-2 viral sequence quantification down to the attomolar level. Our results demonstrate that a carefully engineered template nanostructure and the AuNP diameter integrate plasmonic hotspots, target adsorption, thermoplasmonic heating, and signal transduction within a single platform. This facile strategy for densely packed hotspots offers a potentially scalable avenue for ultrasensitive biomolecular assays.