Smith, Andrew M.

Tiny silicon microchip–based high-throughput hanging drop arrays allow drug screening and geometric control.

Significance Highly selective and sensitive detection of microRNA is a key challenge in the development of liquid-biopsy approaches. Technologies that can achieve high diagnostic performance without the requirement of complicated processing steps or expensive equipment are necessary for broad use. With these features in mind, we demonstrate a digital-readout microRNA diagnostic that fundamentally relies on microRNA-activated nanoparticle-photonic crystal hybrid coupling. The hybrid formation allows for clear detection of single-particle binding events due to enhanced nanoparticle absorption at the binding location. Whereas the applied photonics lend the assay concentration sensitivity, we additionally demonstrate broad placement single-base mismatch selectivity and complex media detection by applying free-energy tuned toehold probes.