Activating\nSERS Signals of Inactive Analytes: Creating\nan Energy Bridge between Metal/Molecule Energy Alignment via Metal/Semiconductor\nTransitions

Surface-enhanced Raman spectroscopy (SERS) is a powerful\nanalytical\ntechnique, yet it faces challenges with certain probe molecules exhibiting\nweak or inactive signals, limiting their applicability. In a recent\nstudy, we investigated this phenomenon using a set of four probe moleculeschloramphenicol\n(CAP), 4-nitrophenol (4-NP), amoxicillin (AMX), and furazolidone (FZD)deposited\non Ag-based nanostructured SERS substrates. Despite being measured\nunder identical conditions, CAP and 4-NP exhibited SERS activity,\nwhile AMX and FZD did not. We also demonstrated that the alignment\nof the target molecule’s lowest unoccupied molecular orbital\n(LUMO) energy level with the substrate’s Fermi level plays\na critical role in influencing the SERS signal. When the LUMO level\ndiverges from the Fermi level, hindrance of the charge transfer process\noccurs due to a high potential barrier, leading to weak or absent\nSERS signals. To overcome this challenge, in this study, we introduce\nan approach inspired by metal–semiconductor interfacial charge\ntransfer dynamics. By employing TiO<sub>2</sub>/Ag nanostructures,\nwe not only enhance SERS signals for CAP and 4-NP but also activate\nsignals for inactive molecules AMX and FZD. Importantly, we demonstrate\nthat controlling the crystalline phase composition of the TiO<sub>2</sub> semiconductor allows for tailored conduction band minimum\nenergy level (E<sub>CBM</sub>) positions, significantly impacting\nthe overall SERS efficiency of the TiO<sub>2</sub>/Ag substrate. Our\nfindings highlight the pivotal role of the semiconductor’s\nE<sub>CBM</sub> position in the energy alignment of the metal–semiconductor–analyte\nthree-body interaction for an optimal SERS sensing platform. These\nfindings also offer a novel strategy to enhance and activate the SERS\nphenomenon of important yet underexplored analytes.