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 Multidisciplinary Sciences 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 (named Max Planck Institute for Multidisciplinary Sciences since 2022) 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

Sahl, S. J. , J. Matthias, K. Inamdar, M. Weber, T. A. Khan, C. Brüser, S. Jakobs, S. Becker, C. Griesinger, J. Broichhagen, S. W. Hell (2024): "Direct optical measurement of intramolecular distances with angstrom precision".  Science   386, 180 - 187 view

Schleske, J. M. , J. Hubrich, J. O. Wirth, E. D'Este, J. Engelhardt, S. W. Hell (2024): "MINFLUX reveals dynein stepping in live neurons".  PNAS , in early view. view

Bredfeldt, J.-E. , J. Orcaz, Kiszka, K. A., Moosmayer, T., Weber, M., Sahl, S. J., Hell, S. W. (2024): "Bleaching protection and axial sectioning in fluorescence nanoscopy through twophoton activation at 515nm".  nature communications   15:7472, view first published in Open Access

Khan, T. A. , S. Stoldt, M. L. Bossi, V. N. Belov, S. W. Hell (2024): "β-Galactosidase- and Photo-Activatable Fluorescent Probes for Protein Labeling and Super-Resolution STED Microscopy in Living Cells".  molecules   29, view

Rickert, J. D. , M. O. Held, J. Engelhardt, S. W. Hell (2024): "4Pi MINFLUX arrangement maximizes spatio-temporal localization precision of fluorescence emitter".  PNAS , in early view. view

Knorr, G. , M. L. Bossi, A. N. Butkevich, S. W. Hell (2024): "Synthesis of Thioxanthone 10,10-Dioxides and Sulfone-Fluoresceins via Pd-Catalyzed Sulfonylative Homocoupling".  Organic Letters   26, 945 - 949 view

Scheiderer, L. , H. von der Emde, M. Hesselink, M. Weber, S.W. Hell (2024): "MINSTED tracking of single biomolecules".  Nature methods   , view

Remmel, M. , J. Matthias, R. Lincoln, J. Keller-Findeisen, A. N. Butkevich, M. L. Bossi, S. W. Hell (2024): "Photoactivatable Xanthone (PaX) Dyes Enable Quantitative,Dual Color, and Live-Cell MINFLUX Nanoscopy".  small methods , in early view. view first published in Open Access

Wirth, J. O. , E.-M. Schenterra, L. Scheiderer, V. Macarrón-Palacios, M. Tarnawski & S. W. Hell (2024): "Uncovering kinesin dyamics in neurites with MINFLUX".  communications biology , in early view. view

Wolff, J. O. , L. Scheiderer, T. Engelhardt, J. Engehlardt, J. Matthias, S.W. Hell (2023): "MINLUX dissects the unimpeded walking of kinesin-1".  Science   379, 1004-1010  https://www.science.org/stoken/author-tokens/ST-1071/full view first published in BioArxiv

Kim, D. , S. Stoldt, M. Weber, S. Jakobs, V. N. Belov, S. W. Hell (2023): "A Bright Surprise: Live-Cell Labeling with Negatively Charged Fluorescent Probes based on Disulfonated Rhodamines and HaloTag".  Chemistry Methods , in early view.  https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/cmtd.202200076 view

Aktalay, A. , T. A. Khan, M. L. Bossi, V. N. Belov, S. W. Hell (2023): "Photoactivatable Carbo- and Silicon-Rhodamines and Their Application in MINFLUX Nanoscopy".  Angew. Chem. Int. Ed. , in early view.  https://doi.org/10.1002/anie.202302781 view

Landmark Publications

Sahl, S. J. , J. Matthias, K. Inamdar, M. Weber, T. A. Khan, C. Brüser, S. Jakobs, S. Becker, C. Griesinger, J. Broichhagen, S. W. Hell (2024): "Direct optical measurement of intramolecular distances with angstrom precision".  Science   386, 180 - 187 view

Rickert, J. D. , M. O. Held, J. Engelhardt, S. W. Hell (2024): "4Pi MINFLUX arrangement maximizes spatio-temporal localization precision of fluorescence emitter".  PNAS , in early view. 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

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

Eilers, Y. , H. Ta, K. C. Gwosch, F. Balzarotti, S. W. Hell (2018): "MINFLUX monitors rapid molecular jumps with superior spatiotemporal resolution".  PNAS   115, 6117-6122 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

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. , S. O. Rizzoli, V. Westphal, R. Jahn, S. W. Hell (2006): "STED-microscopy reveals that synaptotagmin remains clustered after synaptic vesicle exocytosis".  Nature   440, 935-939 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 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