Orthogonal Sensing of Small Molecules Using a Modular Nanoparticle‐Based Assay

Abstract Herein, we present a modular indicator‐displacement assay able to selectively recognize small molecules with biological relevance under competitive conditions. The assay relies on the change in affinity of macrocyclic receptors, such as cavitands, cyclodextrins or calixarenes, for monolayer‐protected gold nanoparticles upon complexation of the respective target analyte. This change affects the equilibrium between the nanoparticles and a fluorescent reporter leading to a change in intensity of the fluorescent output signal. The recognition modules can be changed in order to tune the selectivity of the assay without affecting the nature of the output signal. The combined use of recognition modules results in an assay able to detect multiple analytes simultaneously with high selectivity.