A Metasurface Plasmonic Analysis Platform Combined with Gold Nanoparticles for Ultrasensitive Quantitative Detection of Small Molecules

Food safety related to drug residues in food has become a widespread public concern. Small-molecule drug residue analysis often relies on mass spectrometry, thin-layer chromatography, or enzyme-linked immunosorbent assays (ELISA). Some of these techniques have limited sensitivity and accuracy, while others are time-consuming, costly, and rely on specialized equipment that requires skilled operation. Therefore, the development of a sensitive, fast, and easy-to-operate biosensor could provide an accessible alternative to conventional small-molecule analysis. Here, we developed a nanocup array-enhanced metasurface plasmon resonance (MetaSPR) chip coupled with gold nanoparticles (AuNPs) (MSPRAN) to detect small molecules. As sulfamethazine drug residues in poultry eggs may cause health issues, we selected this as a model to evaluate the feasibility of using MSPRAN for small-molecule detection. The MSPRAN biosensor employed competitive immunoassay technology for sulfamethazine detection. The limit of detection was calculated as 73 pg/mL, with sensitivity approximately twice that of previously reported detection methods. Additionally, the recovery rate of the biosensor, tested in egg samples, was similar to that measured using ELISA. Overall, this newly developed MSPRAN biosensor platform for small-molecule detection provides fast and reliable results, facile operation, and is relatively cost-effective for application in food safety testing, environmental monitoring, or clinical diagnostics.