How to detect weak pairs

Single-molecule fluorescence spectroscopy has shed light on many biological processes, from protein folding to enzyme dynamics. However, to study weakly interacting molecules, the diffraction limit of light must be overcome. In their Perspective, Laurence and Weiss review recent "superresolution" methods that achieve smaller detection volumes, a requirement for studying weak interactions. They highlight the method of Levene et al., who achieve parallel detection of many single molecules in extremely small (zeptoliter) detection volumes.