Based on sensitively detecting one fluorescent dye at a time, single-molecule fluorescence imaging gives nanometer-scale resolution to benchtop optical microscopes, enabling in situ and in vivo super-resolution microscopy. Still, the resolution of single-molecule fluorescence imaging is limited by the brightness of fluorescent probes. To address this limitation, we take advantage of the localized surface plasmon resonances that result from the interaction of light with metal nanoparticles to improve the brightness and photostability of nearby fluorescent labels. We have measured plasmon-enhanced fluorescence one dye at a time in a single-molecule approach that eliminates ensemble averaging.

Furthermore, by measuring the fundamental properties of plasmon-enhanced fluorescence with single-molecule detection, we have discovered how coupling leads to a predictable shift of the emission position, angle, and polarization. Finally, we are applying this understanding to biocompatible enhancement of fluorescent protein emission, extending the advantages of metal-enhanced fluorescence to live-cell bio-imaging, and creating a flexible technology for high-resolution, real-time imaging.