Chemistry is, for the most part, a field of ensemble measurements. Large numbers of molecules acting together produce effects that are macroscopically observable. But in many cases, such as the study of inhomogeneous systems or of processes with complex time dependence, observing molecules one by one can provide information that an ensemble measurement cannot.
Much of the flavor of single-molecule optical detection—a less invasive technique than, for example, scanning tunneling microscopy—dates back to 1976, when Tomas Hirschfeld used an optical microscope to observe proteins tagged with tens of fluorescent molecules. 1 True single-molecule detection came in 1989-90, achieved independently by William Moerner and Michel Orrit and their colleagues. 2 Both worked at cryogenic temperatures, at which molecular spectral peaks are much stronger and sharper. Room-temperature detection came shortly thereafter and has since facilitated a multitude of advances in biology, materials science, and other fields. Among the more striking recent...
