Dual Optimization of Shell and Interparticle Gaps in Plasmonic Au@Ag Nanocubes Assembly for Hot Spot-Driven SERS Performance

Surface-enhanced Raman scattering (SERS) allows sensitive detection of low-concentration biomolecules by amplifying Raman signals through plasmonic nanoparticles (NPs) such as Au@Ag nanostructures possessing tailorable surface plasmon resonance (SPR). This study presents a seed-mediated growth approach for the synthesis of monodisperse Au@Ag core-shell nanocubes. Their tunable cubic shell thickness (<i>t</i>_s) and self-assembly-induced controlled interparticle gaps (IPG) could act as dual optimization for SPR-enabled SERS enhancement. The thickness of the Ag shell is precisely controlled by varying the AgNO₃ concentration. Structural and optical characterizations were conducted by using UV-visible spectroscopy, high-resolution transmission electron microscopy (HRTEM), and X-ray diffraction (XRD). The uniform assembly-produced IPG was regulated and achieved by tailoring the concentration of the surfactant CTAB. The SERS performance was evaluated using novel antibodies (aCD47) as a probe molecule, demonstrating that SERS intensity can be effectively optimized by tuning the core-shell composition and IPG. The SERS enhancement factor (EF) of ∼5 × 10⁶ was achieved from Au@Ag nanocubes assembly with <i>t</i>_s and IPG below 10 nm, highlighting strong electromagnetic hotspot formation. The experimentally observed hotspot generation at different <i>t</i>_s and IPG was further backed by numerical simulations using COMSOL Multiphysics.