Highly uniform and reproducible surface-enhanced Raman scattering from DNA-tailorable nanoparticles with 1-nm interior gap

An ideal surface-enhanced Raman scattering (SERS) nanostructure for sensing and imaging applications should induce a high signal enhancement, generate a reproducible and uniform response, and should be easy to synthesize. Many SERS-active nanostructures have been investigated, but they suffer from poor reproducibility of the SERS-active sites, and the wide distribution of their enhancement factor values results in an unquantifiable SERS signal. Here, we show that DNA on gold nanoparticles facilitates the formation of well-defined gold nanobridged nanogap particles (Au-NNP) that generate a highly stable and reproducible SERS signal. The uniform and hollow gap (∼1 nm) between the gold core and gold shell can be precisely loaded with a quantifiable amount of Raman dyes. SERS signals generated by Au-NNPs showed a linear dependence on probe concentration (R²>0.98) and were sensitive down to 10 fM concentrations. Single-particle nano-Raman mapping analysis revealed that >90% of Au-NNPs had enhancement factors greater than 1.0 × 10 ⁸, which is sufficient for single-molecule detection, and the values were narrowly distributed between 1.0 × 10⁸ and 5.0 × 10⁸.