High-Throughput Fabrication of Microscale Gold Nanoparticle Superstructures with Tunable Plasmonic Coupling for Ultrasensitive SERS Detection

Noble metal nanostructures are attractive substrates for surface-enhanced Raman scattering (SERS) but face persistent challenges in combining efficient hot-spot engineering with scalable fabrication. This paper presents a high-throughput, hot-spot-designable approach for assembling gold nanoparticles (AuNPs) onto micrometer-scale, two-dimensional polymer single-crystal templates, producing ∼10⁸ uniform AuNP assemblies per milliliter. The assemblies, with planar micrometer-scale dimensions, are fully compatible with commercial confocal Raman systems. AuNP shape (spherical or anisotropic) is controlled through chemical reduction kinetics. Systematic SERS measurements reveal that precisely assembled spherical AuNPs with sub-2 nm gaps generate strong local electromagnetic field enhancement, yielding an analytical enhancement factor (AEF) of 1.43 × 10⁶. Compared with a commercial macroscopic SERS substrate of monolayer AuNPs, the proposed substrate delivers a 28-fold higher signal intensity while requiring 98% less AuNP surface coverage. Its applicability is demonstrated by the detection of biomolecules in sweat and malondialdehyde. This method provides a scalable route for high-throughput molecular sensing in real-world applications.