Throughout the 20th century it was widely accepted that a light microscope relying on conventional optical lenses cannot discern details that are much finer than about half the wavelength of light (200-400 nm), due to diffraction. However, in the 1990s, the viability to overcome the diffraction barrier was realized and microscopy concepts defined, that can resolve fluorescent features down to molecular dimensions. In this lecture, I will discuss the simple yet powerful principles that allow neutralizing the limiting role of diffraction1,2. In a nutshell, feature molecules residing closer than the diffraction barrier are transferred to different (quantum) states, usually a bright fluorescent state and a dark state, so that they become discernible for a brief period of detection. Thus, the resolution-limiting role of diffraction is overcome, and the interior of transparent samples, such as living cells and tissues, can be imaged at the nanoscale.
1. Hell, S.W. Far-Field Optical Nanoscopy. Science 316, 1153-1158 (2007).
2. Hell, S.W. Microscopy and its focal switch. Nature Methods 6, 24-32 (2009).
Meet Dr. Stefan Hell
Stefan W. Hell is a Director at the Max Planck Institute for Biophysical Chemistry in Göttingen, where he leads the Department of NanoBiophotonics. Since 2016 he is also a Director at the Max Planck Institute for Medical Research in Heidelberg, where he leads the Department of Optical Nanoscopy.
Stefan W. Hell received his diploma (1987) and doctorate (1990) in physics from the University of Heidelberg. From 1991 to 1993 he worked at the European Molecular Biology Laboratory, also in Heidelberg, followed by stays as a senior researcher at the University of Turku, Finland, between 1993 and 1996, and as a visiting scientist at the University of Oxford, England, in 1994. In 1997 he was appointed to the MPI for Biophysical Chemistry in Göttingen as a group leader and was promoted to Director in 2002.
Hell is credited with having conceived, validated and applied the first viable concept for overcoming Abbe’s diffraction-limited resolution barrier in a light-focusing fluorescence microscope. For these achievements and their significance for other fields, Hell has received numerous awards. In 2014 he shared the Kavli Prize in Nanoscience and the Nobel Prize in Chemistry.