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Molecular-size resolution with light

Throughout the 20th century, it was widely accepted that a light microscope relying on propagating light waves and conventional optical lenses could not discern details that were much finer than about half the wavelength of light, or 200-400 nm, due to diffraction.

Stefan Hell and his team have shattered what was regarded an absolute limit of microscopic resolution. For his development of STED (STimulated Emission Depletion) microscopy, the first light-focusing microscope with a resolution at the nanoscale, Stefan Hell was awarded the Nobel Prize in Chemistry in 2014.

Recently, a fresh look at the basic physical principles underlying nanoscopy has spawned powerful new concepts. In particular, MINFLUX imaging (nanoscopy with MINimal photon FLUXes) has been pioneered in the Hell Labs, obtaining the ultimate (super)resolution: the size of a molecule (~1 nm). At present, MINFLUX and related concepts are explored to create unprecedented measurement capabilities for the life sciences and beyond.

Picture of Stefan W. Hell

Stefan W. Hell

Stefan Hell is a director at both the Max Planck Institute for Biophysical Chemistry in Göttingen and the Max Planck Institute for Medical Research in Heidelberg, Germany.

He 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 numerous awards, including the 2014 Kavli Prize in Nanoscience and the Nobel Prize in Chemistry.

Stefan Hell received his doctorate (1990) in physics from the University of Heidelberg. From 1991 to 1993 he worked at the European Molecular Biology Laboratory, 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. From 2003 to 2017 he also led a research group at the German Cancer Research Center (DKFZ). Hell holds honorary professorships in physics at the Universities of Heidelberg and Göttingen.

Stefan Hell’s Autobiography at nobelprize.org  |  Stefan Hell’s Nobel Lecture (Video)

Most Recent Articles

Lohner, P. , M. Zmyslia, J. Thurn, J. K. Pape, R. Gerasimaite, J. Keller-Findeisen, S. Groeer, B. Deuringer, R. Süss, A. Walther, S. W. Hell, G. Lukinavicius, T. Hugel, C. Jessen-Trefzer (2021): "Inside a Shell – Organometallic Catalysis Inside Encapsulin Nanoreactors".  Angew. Chem. Int. Ed. , in early view. view

Konen, T. , D. Stumpf, T. Grotjohann, I. Jansen, M. Bossi, M. Weber, N. Jensen, S. W. Hell, S. Jakobs (2021): "The Positive Switching Fluorescent Protein Padron2 Enables Live-Cell Reversible Saturable Optical Linear Fluorescence Transitions (RESOLFT) Nanoscopy without Sequential Illumination Steps".  ACS Nano    , 9509-9521 view

Gerasimaite, R. , Bucevicius, J., Kiszka, K. A., Schnorrenberg, S., Kostiuk, G., Koenen, T., Lukinavicius, G. (2021): "Blinking Fluorescent Probes for Tubulin Nanoscopy in Living and Fixed Cells".  ACS Chem. Biol. , in early view. view

Savicheva, E. A. , J. Seikowski, J. I. Kast, C. R. Grünig, V. N. Belov, S. W. Hell (2021): "Fluorescence Assisted Capillary Electrophoresis of Glycans Enabled by the Negatively Charged Auxochromes in 1‐Aminopyrenes".  Angew. Chem. Int. Ed.    , 3720-3726 view

Uno, K. , A. Aktalay, M. L. Bossi, M. Irie, V. N. Belov, S. W. Hell (2021): "Turn-on mode diarylethenes for bioconjugation and fluorescence microscopy of cellular structures".  PNAS    118, view

Weber, M. , M. Leutenegger, S. Stoldt, S. Jakobs, T. S. Mihaila, A. N. Butkevich, S. W. Hell (2021): "MINSTED fluorescence localization and nanoscopy".  Nature Photonics    15, 361-366  Additionally published in bioRxiv view

Schmidt, R. , T. Weihs, C. A. Wurm, I. Jansen, J. Rehman, S. J. Sahl, S. W. Hell (2021): "MINFLUX nanometer-scale 3D imaging and microsecond-range tracking on a common fluorescence microscope".  Nature Commun.    , view

Quentin, C. , R. Gerasimaite, A. Freidzon, L. S. Atabekyan, G. Lukinavicius, V. N. Belov, G. Mitronova (2021): "Direct Visualization of Amlodipine Intervention into Living Cells by Means of Fluorescence Microscopy".  molecules    , view

Landmark Publications

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

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

Chojnacki, J. , T. Staudt, B. Glass, P. Bingen, J. Engelhardt, M. Anders, J. Schneider, B. Müller, S. W. Hell, H.-G. Kräusslich (2012): "Maturation-Dependent HIV-1 Surface Protein Redistribution Revealed by Fluorescence Nanoscopy".  Science    338, 524 - 528 view

Berning, S. , K. I. Willig, H. Steffens, P. Dibaj, S. W. Hell (2012): "Nanoscopy in a Living Mouse Brain".  Science    335, 551 view

Grotjohann, T. , I. Testa, M. Leutenegger, H. Bock, N. T. Urban, F. Lavoie-Cardinal, K. I. Willig, C. Eggeling, S. Jakobs, S. W. Hell (2011): "Diffraction-unlimited all-optical imaging and writing with a photochromic GFP".  Nature    478, 204 - 208 view

Hell, S. W. (2007): "Far-Field Optical Nanoscopy".  Science    316, 1153-1158 view

Willig, K. I. , R. R. Kellner, R. Medda, B. Hein, S. Jakobs, S. W. Hell (2006): "Nanoscale resolution in GFP-based microscopy".  Nature Meth.    3, 721-723 view

Westphal, V. , S. W. Hell (2005): "Nanoscale Resolution in the Focal Plane of an Optical Microscope".  Phys. Rev. Lett.    94, 143903 (4 pp.) view

Klar, T. A. , S. Jakobs, M. Dyba, A. Egner, S. W. Hell (2000): "Fluorescence microscopy with diffraction resolution limit broken by stimulated emission".  PNAS    97, 8206-8210Abstract view

Hell, S. W. , J. Wichmann (1994): "Breaking the diffraction resolution limit by stimulated emission: stimulated-emission-depletion fluorescence microscopy".  Opt. Lett.    19, 780-782  We propose a new type of scanning fluorescence microscope capable of resolving 35 nm in the far field. We overcome the diffraction resolution limit by employing stimulated emission to inhibit the fluorescence process in the outer regions of the excitation point-spread function. In contrast to near-field scanning optical microscopy, this method can produce three-dimensional images of translucent specimens. view

Address


Max Planck Institute for Biophysical Chemistry
Department of NanoBiophotonics
Am Fassberg 11, 37077 Göttingen, Germany
&
Max Planck Institute for Medical Research
Department of Optical Nanoscopy
Jahnstr. 29, 69120 Heidelberg, Germany

Phone


+49 551 201 2500