Pauli Lectures 2017

The Wolfgang Pauli Lectures 2017 were dedicated to physics.

Prof. Stefan W. Hell

Max Planck Institute for Biophysical Chemistry, Göttingen &
Max Planck Institute for Medical Research, Heidelberg

Enlarged view: Copyright: Scanpix
Copyright: Scanpix

Stefan W. Hell is a director at the external pageMax Planck Institute for Biophysical Chemistry in Göttingen, where he leads the Department of NanoBiophotonics. He is an honorary professor of experimental physics at the external pageUniversity of Göttingen and adjunct professor of physics at the external pageUniversity of Heidelberg. Since 2003 he also led the external pageOptical Nanoscopy division at the external pageGerman Cancer Research Center (DKFZ) in Heidelberg.

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, and followed with 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 in 2002 to director. In 2016 he was additionally promoted to director at the Max Planck Institute for Medical Research in Heidelberg.

Stefan W. 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 this accomplishment he has received several awards: most recently he shared the 2014 Kavli Prize in Nanoscience and the Nobel Prize in Chemistry.

How I Got to Break the Diffraction Barrier of Optical Microscopy

Monday, May 22, 2017 (17:15 h) Auditorium Maximum, HG F 30, ETH Zentrum, Rämistrasse 101, Zurich

In this lecture for a general audience, without requiring a science background, I will tell my personal story in science. My work on breaking the diffraction barrier has enabled optical microscopes which deliver much sharper images than was previously believed ever to be possible. The optical “nanoscopes” based on this discovery find increasing application in the biomedical sciences, revealing the organization of molecules in cells and tissues in unprecedented detail.

I discuss my path, from the graduate student who dreamt of something exciting to do, to the postdoc and young group leader struggling to find acceptance of my ideas, to the established scientist still continuing to ask what’s next. It is a story of persistence and dedication. As I put it in my Nobel Banquet Speech in Stockholm on December 10, 2014, it is important to seek out something important and then to focus: "We have so many choices of what to do or what to leave – every morning, every day. I better judge for myself, and --- go ahead and do it."   

 

 

 

Nanoscopy with Focused Light

Tuesday, May 23, 2017 (17:15 h) Auditorium Maximum, HG F 30, ETH Zentrum, Rämistrasse 101, Zurich

Throughout the 20th century it was widely accepted that, at the end of the day, a light microscope relying on conventional lenses (far-field optics) cannot discern details that are finer than about half the wavelength of light (>200 nm). However, in the 1990s, it was discovered that overcoming the diffraction barrier is realistic and that fluorescent samples can be resolved virtually down to molecular dimensions. Here I discuss the simple yet powerful principles that allow to neutralize the resolution-limiting role of diffraction and have led to the emergence of STED microscopy and, more generally, to far-field optical ‘nanoscopy’ as an entire field. In a nutshell, features residing closer than the diffraction barrier are prepared in different molecular (quantum) states so that they are distinguishable for a brief detection period. As a result, the resolution-limiting role of diffraction is overcome, and the interior of transparent samples such as living cells and tissues can now be imaged with nanoscale resolution using focused light in 3D. I illustrate the power of nanoscopy with a few examples from biology, to show what exciting opportunities lie ahead.

Optical Nanoscopy: Concepts and Recent Advances

Wednesday, May 24, 2017 (15:30 h) Lecture Room HCI G 3, ETH Hönggerberg, Vladimir-Prelog-Weg 1-5/10, Zurich

Throughout the 20th century it was widely accepted that, at the end of the day, a light microscope relying on conventional lenses (far-field optics) cannot discern details that are finer than about half the wavelength of light (>200 nm). However, in the 1990s, it was discovered [1] that overcoming the diffraction barrier is realistic and that fluorescent samples can be resolved virtually down to molecular dimensions.

Here I discuss the simple yet powerful principles that allow to neutralize the resolution-limiting role of diffraction and have led to the emergence of STED microscopy and, more generally, to far-field optical ‘nanoscopy’ as an entire field [2,3]. In a nutshell, features residing closer than the diffraction barrier are prepared in different molecular (quantum) states so that they are distinguishable for a brief detection period. As a result, the resolution-limiting role of diffraction is overcome, and the interior of transparent samples such as living cells and tissues can now be imaged with nanoscale resolution using focused light in 3D.

Moreover, I will show that an in-depth description of these basic principles spawns new powerful concepts such as MINFIELD [4] and MINFLUX nanoscopy [5]. Although they differ in some aspects, both concepts harness a local intensity minimum (of a doughnut or a standing wave) for determining the coordinate of the fluorophore to be registered. Most strikingly, by using an excitation intensity minimum to establish the fluorophore position, MINFLUX nanoscopy has obtained the ultimate (super)resolution: the size of a molecule [5].

[1]  Hell, S.W., Wichmann, J. Breaking the diffraction resolution limit by stimulated emission: stimulated-emission-depletion fluorescence microscopy. Opt. Lett. 19, 780-782 (1994)

[2]  Hell, S.W. Far-Field Optical Nanoscopy. Science 316, 1153-1158 (2007)

[3]  Hell, S.W. Microscopy and its focal switch. Nat. Methods 6, 24-32 (2009)

[4]  Göttfert, F., Pleiner, T., Heine, J., Westphal, V., Görlich, D., Sahl, S.J., Hell, S.W., Strong signal increase in STED fluorescence microscopy by imaging regions of subdiffraction extent. PNAS 114, 2125-2130 (2017)

[5] Balzarotti, F., Eilers, Y., Gwosch, K. C., Gynnå, A. H., Westphal, V., Stefani, F. D., Elf, J., Hell, S.W. Nanometer resolution imaging and tracking of fluorescent molecules with minimal photon fluxes. Science 355, 606-612 (2017)

 

 

 

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