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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  |  Stefan Hell’s Nobel Lecture (Video)

Most Recent Articles

Schnorrenberg, S. , Ghareeb, H.; Frahm, L.; Grotjohann, T.; Jensen, N.; Teichmann, T.; Hell, S.W.; Lipka, V.; Jakobs, S. (2020): "Live-cell RESLOFT nanoscopy of transgenic Arabidopsis thaliana".  Wiley , in early view. view

Pape, J. K. , Stephan, T., Balzarotti, F., Büchner, R., Lange, F., Riedel, D., Jakobs, S., Hell, S.W. (2020): "Multicolor 3D MINFLUX nanoscopy of mitochondrial MICOS proteins".  PNAS    117, 20607-20614. view

Bucevicius, J. , Kostiuk, G.; Gerasimaite, R.; Gilat, T.; Lukinavicius, G. (2020): "Enhancing the biocompatibility of rhodamine fluorescent probes by a neighbouring group effect".  RSC Chemical Science    11, 7313-7323. view

Stephan, T. , Brüser, C., Deckers, M., Steyer, A.M., Balzarotti, F., Barbot, M., Behr, T.S., Heim, G., Hübner, W., Ilgen, P., Lange, F., Pacheu-Grau, D., Pape, J.K., Stoldt, S., Huser, T., Hell, S.W., Möbius, W., Rehling, P., Riedel, D., Jakobs, S. (2020): "MICOS assembly controls mitochondrial inner membrane remodeling and crista junction redistribution to mediate cristae formation".  The EMBO Journal    39, 1-24. view

Belov, V. N. , Stoldt, S., Rüttger, F., John, M., Seikowski, J., Schimpfhauser, J., Hell, S.W. (2020): "Synthesis of Fluorescent Jasplakinolide Analogues for Live-Cell STED Microscopy of Actin".  The Journal of Organic Cemistry    , 7267-7275. view

Gwosch, K. C. , J. K. Pape, F. Balzarotti, P. Hoess, J. Ellenberg, J. Ries, S. W. Hell (2020): "MINFLUX nanoscopy delivers 3D multicolor nanometer resolution in cells".  Nature Meth.    17, 217-224. view

Fomin, M. , Seikowski, J., Belov, V. N., Hell, S. W. (2020): "Negatively Charged Red-Emitting Acridine Dyes for Facile Reductive Amination, Separation, and Fluorescent Detection of Glycans Maksim A.".  Anal. Chem.    92, 5329 - 5336. view

Savicheva, E.A. , Mitronova, G.Y., Thomas, L., Böhm, M.J., Seikowski, J., Belov, V.N., Hell, S.W. (2020): "Negatively Charged Yellow-Emitting 1-Aminopyrene Dyes for Reductive Amination and Fluorescence Detection of Glycans".  Angew. Chem. Int. Ed.    59, 5505 - 5509. view

Gerasimaite, R. , Seikowski, J., Schimpfhauser, J., Kostiuk, G., Gilat, T., D'Este, E., Schnorrenberg, S., Lukinavicius, G. (2020): "Efflux pump insensitive rhodamine-jasplakinolide conjugates for G- and F-actin imaging in living cells".  Organic Biomolecular Chemistry    , 2929-2937. view

Uno, K. , M.L. Bossi, V.N. Belov, M. Irie, S.W. Hell (2020): "Multicolour fluorescent "sulfide-sulfone" diarylethenes with high photo-fatigue resistance".  Chemical Communications    56, 2198-2201. view

Gregor, C. (2020): "Bioluminescent Imaging of Single Bacterial Cells Using an Enhanced ilux Operon".  Steven Ripp (ed.), Bioluminescent Imaging    Chapter 4, 42-52. 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, 8206-8210. 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. view


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


+49 551 201 2500