Enabled by proteins, we present an all-electrical method for rapid detection of small pharmaceuticals (ibuprofen and sulfamethoxazole, SMZ) in aqueous media using silicon nitride pores. Specifically, we use carrier proteins, bovine serum albumin (BSA) and take advantage of their interactions with two small drug molecules to form BSA-drug complexes which can be detected by nm-diameter pores, thereby confirming the presence of small pharmaceuticals. We demonstrate detection of ibuprofen and SMZ at concentrations down to 100 nM (∼ 21 μg/L) and 48.5 nM (∼ 12 μg/L), respectively. We observe changes in electrical signal characteristics (reflected in event durations, rates, current magnitudes and estimated particle diameters) of BSA-drug complexes compared to BSA-only, and differences between these two small pharmaceuticals, possibly paving a path towards developing selective sensors by identifying “electrical fingerprints” of these molecules in the future. These distinct electrical signals are likely a combined result of diffusion, electrophoretic and electroosmotic effects, interactions between the pore and particles, which depend on pore diameters, pH, and the resulting surface charges. The use of single-molecule-counting nanopores allows sensing of small pharmaceuticals, studies of protein conformational changes, and may aid in efforts to evaluate the impact of small drug molecules on aquatic and human life.

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