High-efficiency single molecule fluorescence detection and correlation spectroscopy with dielectric microspheres

Microspheres made of high refractive index melamine resin are shown to enhance the fluorescence from single molecules in solution by seven-fold, and simultaneously reduce the observation volume by thirteen-fold, as compared to state-of-the-art confocal microscopy. This fluorescence enhancement is demonstrated to dramatically increase the signal-to-noise ratio in fluorescence correlation spectroscopy and reduce the experiment integration time by fifty-fold. We also provide the first description of dual-color fluorescence cross-correlation spectroscopy (FCCS) enhanced by a dielectric microsphere, and report comparable enhancement factors as for the single color case.