Unimolecular Cucurbit[7]uril-Based Indicator Displacement Assay with Dual Signal-Readout for the Detection of Drugs

Point-of-care diagnostics relies on optical and electrochemical sensors to develop devices that are both compact and cost-effective. Therefore, the search for new design principles for chemosensors that enable multiple signal outputs is a particularly interesting concept. In this work, we present an unimolecular chemosensor based on cucurbit[7]uril that combines two signal readouts - namely fluorescent and electrochemical signals - in a single chemosensor design. This is achieved by utilizing the tunable fluorescence and the electrochemical properties of the reporter molecule, which depend on whether or not it is engulfed by the cucurbit[7]uril cavity in the absence or presence of the analyte. By setting up an assay using the dual readout chemosensor, illicit drug formulations containing pancuronium bromide or nicotine can be detected at low micromolar concentrations (0–100 μM). This assay is compatible with standard fluorescence plate readers and electrochemical devices, including commercially available screen-printed electrodes. Overall, the chemosensor presented in this study represents a significant advance in the development of cucurbit[7]uril chemosensors, characterized by multimodal detection capabilities. It uniquely combines traditional optical and electrochemical detection methods in a single molecular design.