Cu/Ag Nanoparticle-Based Surface-Enhanced Raman Scattering Substrates for Label-Free Bacterial Detection

Surface-enhanced Raman spectroscopy (SERS) is a promising analytical technique for fast and accurate disease detection due to its attractive features. However, realizing label-free direct detection is still challenging as most probes have extremely low Raman cross sections and little affinity to SERS substrates. Disappointingly, SERS spectra of most bacteria and other biological samples look similar as the differences in their molecular compositions are subtle and not detectable. Hence, the fabrication of highly enhancing plasmonic nanoparticles with excellent uniformity is demanded. Moreover, as SERS substrates are not reusable, cost-effective and simplistic fabrication methods are critical. Here, we report a facile approach to synthesizing Ag nanoparticle array on Cu-foil in less than 3 min, using only Cu-foil, silver nitrate, and hydroquinone. We employed the idea of galvanic replacement in combination with a seed mediated particle-growth approach. The label-free bacterial detection has shown that our Cu/Ag nanoparticle substrate is superior to highly acclaimed Ag nanocubes. Creating strong second and third-generation SERS hot-spots through cooperative interaction of homo-(Ag-Ag) and heterogeneous (Ag-Cu) surfaces contributes mainly to the observed excellent enhancement. Interestingly, direct liquid bacteria sample analysis showed a 6-fold higher detection sensitivity than completely dried samples. We believe that our approach will offer remarkable advantages and change how SERS substrates are prepared and conducted in SERS-based bacterial detection.