A (Relatively) Simple Method to Visualize Single Molecules

Fluorescence microscopy can be used to study certain single molecules in solution or attached to a surface. Two conflicting challenges to overcome are: (1) to image freely moving molecules for long times and (2) to image immobilized single molecules when there is a highly fluorescent background. The fact that these two goals are inversely related is illustrated by epifluorescence, which is good for observing freely diffusing molecules but poor for detecting single molecules, whereas the reverse is true for zero-mode waveguides. Plus, these and other techniques require elaborate (read: expensive) equipment with computerized controls. Sabrina Leslie, Alexander Fields, and Adam Cohen have developed an ingenious (relatively) simple technique that can image freely moving single molecules.