Light paves the way to single-molecule detection and photocontrol, foundations of super-resolution microscopy

More than 25 years ago, low temperature experiments aimed at establishing the ultimate limits to optical storage in solids led to the first optical detection and spectroscopy of a single molecule in the condensed phase. At this unexplored ultimate limit, many surprises occurred where single molecules showed both spontaneous changes (blinking) and light-driven control of emission, properties that were also observed in 1997 at room temperature with single green fluorescent protein variants. These observations form foundations for super-resolution microscopy beyond the diffraction limit with single molecules, and tracking of single molecules in cells continues to yield surprises.