Jaeon Cho, Lijun Peng, Chang Liu
Per- and polyfluoroalkyl substances (PFAS) are a category of persistent and extensively spread environmental contaminants that have raised significant global concerns. Liquid chromatography-tandem mass spectrometry (LC-MS/MS), a conventional detection gold standard, can accurately identify them, but its drawbacks include high costs, complicated procedures, and limited portability. Therefore, we developed a nanopore-based single-molecule sensing platform that combines cyclodextrin (CD) host-guest interactions to achieve precise identification of PFAS. By employing an α-hemolysin (α-HL) biological nanopore, when each CD-PFAS complex interacts with the pore, it creates a unique ionic current blockade that discriminates homologous compounds for single-molecular sensing, such as perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS). Molecular dynamics simulations combined with experimental data reveal the structural and energetic foundations of CD-PFAS interactions. This work demonstrates a sensitive and selective platform for PFAS monitoring, paving the way toward environmental protection.