Activating SERS Signals of Inactive Analytes: Creating an Energy Bridge between Metal/Molecule Energy Alignment via Metal/Semiconductor Transitions

Surface-enhanced Raman spectroscopy (SERS) is a powerful analytical technique, yet it faces challenges with certain probe molecules exhibiting weak or inactive signals, limiting their applicability. In a recent study, we investigated this phenomenon using a set of four probe molecules─chloramphenicol (CAP), 4-nitrophenol (4-NP), amoxicillin (AMX), and furazolidone (FZD)─deposited on Ag-based nanostructured SERS substrates. Despite being measured under identical conditions, CAP and 4-NP exhibited SERS activity, while AMX and FZD did not. We also demonstrated that the alignment of the target molecule's lowest unoccupied molecular orbital (LUMO) energy level with the substrate's Fermi level plays a critical role in influencing the SERS signal. When the LUMO level diverges from the Fermi level, hindrance of the charge transfer process occurs due to a high potential barrier, leading to weak or absent SERS signals. To overcome this challenge, in this study, we introduce an approach inspired by metal-semiconductor interfacial charge transfer dynamics. By employing TiO₂/Ag nanostructures, we not only enhance SERS signals for CAP and 4-NP but also activate signals for inactive molecules AMX and FZD. Importantly, we demonstrate that controlling the crystalline phase composition of the TiO₂ semiconductor allows for tailored conduction band minimum energy level (E_CBM) positions, significantly impacting the overall SERS efficiency of the TiO₂/Ag substrate. Our findings highlight the pivotal role of the semiconductor's E_CBM position in the energy alignment of the metal-semiconductor-analyte three-body interaction for an optimal SERS sensing platform. These findings also offer a novel strategy to enhance and activate the SERS phenomenon of important yet underexplored analytes.