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We present a versatile, tuneable, and selective nanoparticle-based lectin biosensor, based on flocculation of ternary supramolecular nanoparticle networks (NPN), formed through the sequential binding of three building blocks. The three building blocks are β-cyclodextrin-capped CdTe quantum dots, tetraethylene glycol-tethered mannose-adamantane cross-linkers (ADTEGMan), and the tetravalent lectin Concanavalin A (ConA). The working principle of this selective sensor lies in the dual orthogonal molecular interactions of the linker, uniting adamantane-β-cyclodextrin and mannose-lectin interaction motifs, respectively. Only when the lectin is present, sequential binding takes place, leading to in situ self-organization of the sensor through the formation of ternary supramolecular networks. Monitoring the loss of fluorescence signal of the quantum dots in solution, caused by controlled network formation and consecutive flocculation and sedimentation, leads to selective, qualitative, and quantitative lectin detection. Fluorescent sedimented networks can be observed by the naked eye or under UV illumination for a lectin concentration of up to 10-8 M. Quantitative detection is possible at 100 min with a lower detection limit of approximately 5 × 10-8 M.
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