Enhancement of Nanoparticle-based Biomolecular Reactions with Acoustic Stimulation

The application of rapid bio-diagnostic methods is often limited due to their low sensitivity. Current strategies to enhance detection often rely on developing more sensitive physical readouts to report the analyte binding. These advancements, however, are fundamentally constrained by analyte-binding events, which can be tuned through an intricate molecular design only with moderate efficiency. To overcome these limitations, we established an approach for acoustically stimulated reactions between nanoparticles and analyte molecules for enhancing biorecognition sensitivity.

By leveraging acoustic stimulation, we modulated the dynamic behavior of nanoparticles interactions and clustering behavior, as mediated by biomolecular analyte. We applied this approach to both nucleic acid and pathogen antibody-antigen systems, and investigated the key parameters affecting the acoustically stimulated reactions. Our study reveals a several-order improvement in sensitivity for the specific spatiotemporal stimulation profiles. We combined nanoscale characterization with modeling to reveal the mechanism of the observed reaction enhancement effect. The discovered phenomena might find applications in improving detection methods by allowing the identification of low analyte concentrations across various biotargets.