Precisely Controlled Three-Dimensional Gold Nanoparticle Assembly Based on Spherical Bacteriophage Scaffold for Molecular Sensing via Surface-Enhanced Raman Scattering

Surface-enhanced Raman scattering (SERS) induced from nanostructured noble metals has a great potential for molecular detection and analysis. However, it has been a challenge to fabricate a reliable SERS-active nanostructure that produces highly sensitive signal response with high fidelity for use in the practical sensing platform. Here, a bacteriophage MS2 with highly regular structure was introduced as a molecular scaffold to assemble nanoparticles into a dense and reproducible three-dimensional raspberry-shaped nanostructure. The nanoraspberry features evenly distributed electromagnetic hot spots responsible for single-molecule-level analysis of SERS-based sensing. By selecting a rigid molecular linker, as well as MS2 phage, the gold nanoparticles were able to be assembled into nanoraspberry superstructures with precisely defined positions, producing strong electric near-field enhancement between nanometer-sized interparticle gaps. The numerical simulation and experimental measurement demonstrated that the nanoraspberry structure produces strong SERS signal amplification, with remarkable intra- and interbatch signal uniformity, proving that structural reproducibility originated from rigid building blocks can lead to a reliable SERS measurement for molecular sensing and analysis applications.