Dark‐Field Resonance Rayleigh Scattering Biosensor to Monitor Small Molecules and Determine the Secretory Ability of Single Neuron

Abstract Accurate monitoring of small molecules and precise characterization of the secretory ability of neurons are essential for effective diagnosis of neurological diseases. However, existing technologies for monitoring small molecules only provide approximate results. Plasmonic‐based biosensors are a potential solution in this biological application. Nevertheless, optical sensing nanoparticles require precise control of interparticle distance, particle shape and morphology, which can be challenging. This article discovers that the trapping of small molecules to aptamers induces a conformational change that alters the nanostructure of irregularly shaped Au nanoclusters (NCs) and aptamers due to the strong structure‐property relationships of Au NC‐aptamers. This change can be detected via resonance Rayleigh scattering (RRS) intensity in the dark‐field. This new technology overcomes the challenges of precise control of individual nanoparticles and the difficulty of small spectral peak shifts. The Au NC‐aptamers sensing device has a detection limit of 0.112 pm for dopamine, and this work detects 0.226 pm of dopamine surrounding a single epileptic neuron in polarization, which is more than those of healthy neurons. Overall, this easy‐to‐fabricate Au NC‐aptamers‐based technology has a high potential for monitoring small molecules and determining the secretory ability of single neurons, which is not possible using traditional technologies.