Ultrasensitive SERS Detection of Amoxicillin Based on the AgNPs/WS2/AgNPs Hybrid Substrate

Amoxicillin is one of the most widely used antibiotics in modern clinical practices and agricultural breeding. However, it is well documented that high clinical doses of amoxicillin exert carcinogenic, teratogenic, and mutagenic effects in preclinical studies. Therefore, it is essential to develop rapid and accurate detection methods for trace amounts of amoxicillin residues in food matrices. In this work, a AgNPs/WS2/AgNPs composite substrate was fabricated via electron beam evaporation combined with thermal annealing. The proposed sandwich structure doubles the density of plasmonic hotspots and establishes bidirectional charge-transfer channels mediated by few-layer WS2 interlayer between two Ag nanoparticle (AgNP) layers, achieving simultaneous and synergistic amplification of electromagnetic (EM) and chemical (CM) enhancements. The as-prepared AgNPs/WS2/AgNPs substrate enables ultrasensitive detection of amoxicillin with an ultralow limit of detection (LOD) of 10–11 M in aqueous solution, ranking among the best performances of reported semiconductor- and metal-based SERS substrates. For practical applications, amoxicillin with LODs as low as 10–9 M in milk and 10–7 M in commercial orange juice is successfully detected using the composite substrate. Furthermore, the AgNPs/WS2/AgNPs sample exhibits excellent spatial uniformity and maintains good stability when stored under vacuum. It also demonstrated excellent adaptability and favorable molecular selectivity to complex matrices. The quantitative accuracy of detecting amoxicillin using the SERS substrate was validated by the standard LC-MS method. The excellent SERS performance of the AgNPs/WS2/AgNPs hybrid substrate highlights its promising potential as a practical and sensitive SERS platform for antibiotic monitoring in complex matrices.