Circumventing the diffraction limit to achieve nanoscale microscope images has earned Eric Betzig, Stefan W. Hell and W.E. Moerner the 2014 Nobel Prize in Chemistry. Hell, director of the Max Planck Institute for Biophysical Chemistry in Goettingen, Germany, was recognized for developing stimulated emission depletion (STED) microscopy, which uses one laser beam to stimulate fluorescence in molecules and another to cancel out all fluorescence except for that at the nanoscale. Betzig and Moerner, working separately, developed single-molecule microscopy. The method relies on turning individual molecules’ fluorescence on and off. The same area is imaged multiple times, with just a few interspersed molecules allowed to glow each time. Superimposing these images yields a dense image with nanoscale detail. STED microscopy (circular inset image) provides an approximately 10 times sharper image of filament structures within a nerve cell compared to a conventional light microscope (outer image). Courtesy of the Max Planck Institute for Biophysical Chemistry. Betzig, of the Howard Hughes Medical Institute’s Janelia Farm Research Campus in Ashburn, Va., utilized this method for the first time in 2006. Moerner is a professor at Stanford University. “Today, nanoscopy is used worldwide and new knowledge of greatest benefit to mankind is produced on a daily basis,” according to the Royal Swedish Academy of Sciences, which presents the Nobels. The techniques developed by Hell, Betzig and Moerner, according to the society, have enabled scientists to see how molecules create synapses between nerve cells in the brain, track proteins involved in Parkinson’s, Alzheimer’s and Huntington’s diseases, and follow individual proteins in fertilized eggs as they divide into embryos. The three recipients will split a prize of 8 million Swedish kronor (about $1.11 million). Conventional light microscopes reach their resolution limit when two similar objects are closer than 200 nm because the diffraction of light blurs them to a single image feature. In 1837, German microscopist Ernst Abbe declared that this was the limit of microscopy — and so it was for more than a century. But Hell thought differently, and went on to develop the STED technique in 1999. “Back then I intuitively felt that something has not been thought through thoroughly,” he said in a statement. STED microscopy is capable of imaging labelled protein complexes with a separation of 20 to 50 nm. It can also image fast movements within living cells with a resolution of 65 to 70 nm — three to four times better than conventional light microscopes. For more information, visit www.nobelprize.org.