High-repetition-rate femtosecond laser multi-pulse incubation for noble-metal-free Raman sensing enhancement on Sb2S3 substrates

Surface-enhanced Raman scattering (SERS) technology holds great application prospects in biomedicine and food safety detection. Nevertheless, conventional noble metal substrates suffer from high cost and insufficient stability. In this work, a multi-pulse incubation fabrication strategy using high-repetition-rate femtosecond laser is proposed. This method achieves the one-step fabrication of micro/nano-structured SERS substrates on Sb 2 S 3 thin films, which integrate laser-induced periodic surface structures (LIPSS) and in-situ generated nanoparticles. The hybrid micro/nano-structures strongly increase the localized electric field, and facilitates interactions between excitation light and target molecules, as well as further amplify Raman signals. The substrate exhibits excellent trace analysis capability, long-term environmental stability and favorable detection repeatability, with a limit of detection (LOD) of 10 −4 M for urea molecules in saliva samples. Relying on the urease-catalyzed hydrolysis reaction, this substrate can quantify urease levels in saliva, enabling non-invasive preliminary screening for Helicobacter pylori infection. This study offers a new route for the high-efficiency fabrication of noble-metal-free SERS substrates and rapid clinical detection applications.