Tunable Fluorescent Artificial Receptor Biosensor Based on Programmable Lanthanide Metal‐Organic Framework for Highly Selective Neurotransmitter Detection

Abstract The design and fabrication of artificial receptors suitable for highly selective and sensitive sensing of neurotransmitters in aqueous media remains a challenge, especially for the significant biomarker dopamine (DA) for neurological diseases. Herein, a novel modular fluorescent artificial receptor design strategy based on multiple parameters programming engineering is proposed. The optimal artificial receptor DA biosensor based on fluorescent lanthanide metal‐organic frameworks (Ln‐MOFs) is coded by adjusting the modular design parameters such as preparation solvents and ligands. It is prepared by Eu ion and ligand 1,2,4,5‐benzenetetracarboxylic acid (BTEC) in DMF/water, which can selectively recognize DA even in complex biological fluids, without the interference of other structurally similar neurotransmitters such as levodopa, serotonin and noradrenaline, and the limit of detection for DA is as low as 10 n m . Ln‐MOFs are believed to uniquely utilize their tunable host‐guest interactions (specific recognition) and confinement catalysis capabilities to achieve highly selective and dual‐response DA detection, similar to lock‐and‐key theory, which is supported by experiments and density functional theory calculations. Fluorescent artificial receptors based on Ln‐MOFs are proved to have broad potential for label‐free detection, imaging and diagnosis. They can overcome the long‐standing limitations of complex synthetic biosensors, and bringing new solutions to personalized medicine.