Francisco Balzarotti

Last updated
Francisco Balzarotti
Born1983
Alma mater University of Buenos Aires (Diploma, PhD)
Known forMINFLUX, super-resolution microscopy, Single Molecule Tracking, Light Microscopy
Scientific career
Fields physics, electronics, optics, microscopy
Institutions
Website www.balzarotti-lab.org

Francisco Balzarotti (born in 1983 in Buenos Aires, Argentina) is an Argentinian scientist known for his work in super-resolution microscopy, particularly MINFLUX. He is a Group Leader at the Research Institute of Molecular Pathology (IMP) in Vienna, Austria. [1]

Contents

Education

From 2002 to 2007, Balzarotti studied electrical engineering at the University of Buenos Aires in Buenos Aires, Argentina. In 2012, he earned his Ph.D. in Electrical Engineering, working on research topics such as nanophotonics, optical nanolithography, superlenses, and plasmonics. [2] [3]

Career and research

For his postgraduate work, Balzarotti relocated to Germany to work as a postdoctoral researcher in the Department of NanoBiophotonics [4] at the Max Planck Institute for Biophysical Chemistry, led by Nobel Laureate Stefan W. Hell.

In Göttingen, Balzarotti played a central role in developing the super-resolution microscopy method MINFLUX [5] [6] which was named Breakthrough of the Year in 2017 by Physics World. [7] The method was even described as the Holy Grail in Light Microscopy. [8]

MINFLUX combines elements of information theory with the single-emitter nature of PALM/STORM and the beam geometries typically used in STED. During Balzarotti's time in Göttingen, they were able to show that with MINFLUX, a given localization precision can be obtained by using much fewer photons than in conventional centroid-localization techniques such as PALM/STORM. Hence, MINFLUX attains nanometer-scale resolution more quickly and with fewer emitted photons than previously possible. Subsequent work increased the application space of the technology even further. [9] [10] [11]

Since 2020, Balzarotti has been a Group Leader at the Research Institute of Molecular Pathology (IMP) in Vienna, Austria, supported by the European Research Council. At the IMP, he set up the Advanced Microscopy and Biophysics group. [12] [13] [14]

Balzarotti's group focuses on the development of novel optical methods and instrumentation for the observation of biological phenomena with the highest fidelity. His interdisciplinary group combines expertise in physics, engineering, mathematics, and biology.

Balzarotti is a well-known microscopist and an established member of the advanced microscopy community. Hence, he is frequently invited as a keynote speaker at key conferences in the field. [15] [16]

Balzarotti's group in collaboration with Mark Bates, organized the Single Molecule Localization Symposium 2023, which was hosted at IMP in Vienna. [17]

Awards and honours

Related Research Articles

<span class="mw-page-title-main">Microscopy</span> Viewing of objects which are too small to be seen with the naked eye

Microscopy is the technical field of using microscopes to view objects and areas of objects that cannot be seen with the naked eye. There are three well-known branches of microscopy: optical, electron, and scanning probe microscopy, along with the emerging field of X-ray microscopy.

<span class="mw-page-title-main">Optical microscope</span> Microscope that uses visible light

The optical microscope, also referred to as a light microscope, is a type of microscope that commonly uses visible light and a system of lenses to generate magnified images of small objects. Optical microscopes are the oldest design of microscope and were possibly invented in their present compound form in the 17th century. Basic optical microscopes can be very simple, although many complex designs aim to improve resolution and sample contrast.

A total internal reflection fluorescence microscope (TIRFM) is a type of microscope with which a thin region of a specimen, usually less than 200 nanometers can be observed.

Fluorescence correlation spectroscopy (FCS) is a statistical analysis, via time correlation, of stationary fluctuations of the fluorescence intensity. Its theoretical underpinning originated from L. Onsager's regression hypothesis. The analysis provides kinetic parameters of the physical processes underlying the fluctuations. One of the interesting applications of this is an analysis of the concentration fluctuations of fluorescent particles (molecules) in solution. In this application, the fluorescence emitted from a very tiny space in solution containing a small number of fluorescent particles (molecules) is observed. The fluorescence intensity is fluctuating due to Brownian motion of the particles. In other words, the number of the particles in the sub-space defined by the optical system is randomly changing around the average number. The analysis gives the average number of fluorescent particles and average diffusion time, when the particle is passing through the space. Eventually, both the concentration and size of the particle (molecule) are determined. Both parameters are important in biochemical research, biophysics, and chemistry.

A 4Pi microscope is a laser scanning fluorescence microscope with an improved axial resolution. With it the typical range of the axial resolution of 500–700 nm can be improved to 100–150 nm, which corresponds to an almost spherical focal spot with 5–7 times less volume than that of standard confocal microscopy.

<span class="mw-page-title-main">STED microscopy</span> Technique in fluorescence microscopy

Stimulated emission depletion (STED) microscopy is one of the techniques that make up super-resolution microscopy. It creates super-resolution images by the selective deactivation of fluorophores, minimizing the area of illumination at the focal point, and thus enhancing the achievable resolution for a given system. It was developed by Stefan W. Hell and Jan Wichmann in 1994, and was first experimentally demonstrated by Hell and Thomas Klar in 1999. Hell was awarded the Nobel Prize in Chemistry in 2014 for its development. In 1986, V.A. Okhonin had patented the STED idea. This patent was unknown to Hell and Wichmann in 1994.

RESOLFT, an acronym for REversible Saturable OpticaLFluorescence Transitions, denotes a group of optical fluorescence microscopy techniques with very high resolution. Using standard far field visible light optics a resolution far below the diffraction limit down to molecular scales can be obtained.

<span class="mw-page-title-main">Stefan Hell</span> Romanian-German physicist (born 1962)

Stefan Walter Hell is a Romanian-German physicist and one of the directors of the Max Planck Institute for Multidisciplinary Sciences in Göttingen, and of the Max Planck Institute for Medical Research in Heidelberg, both of which are in Germany. He received the Nobel Prize in Chemistry in 2014 "for the development of super-resolved fluorescence microscopy", together with Eric Betzig and William Moerner.

<span class="mw-page-title-main">Max Planck Institute for Medical Research</span>

The Max Planck Institute for Medical Research in Heidelberg, Germany, is a facility of the Max Planck Society for basic medical research. Since its foundation, six Nobel Prize laureates worked at the Institute: Otto Fritz Meyerhof (Physiology), Richard Kuhn (Chemistry), Walther Bothe (Physics), André Michel Lwoff, Rudolf Mößbauer (Physics), Bert Sakmann and Stefan W. Hell (Chemistry).

<span class="mw-page-title-main">GSD microscopy</span> Method of microscopy

Ground state depletion microscopy is an implementation of the RESOLFT concept. The method was proposed in 1995 and experimentally demonstrated in 2007. It is the second concept to overcome the diffraction barrier in far-field optical microscopy published by Stefan Hell. Using nitrogen-vacancy centers in diamonds a resolution of up to 7.8 nm was achieved in 2009. This is far below the diffraction limit (~200 nm).

Christoph Cremer is a German physicist and emeritus at the Ruprecht-Karls-University Heidelberg, former honorary professor at the University of Mainz and was a former group leader at Institute of Molecular Biology (IMB) at the Johannes Gutenberg University of Mainz, Germany, who has successfully overcome the conventional limit of resolution that applies to light based investigations by a range of different methods. In the meantime, according to his own statement, Christoph Cremer is a member of the Max Planck Institute for Chemistry and the Max Planck Institute for Polymer Research.

<span class="mw-page-title-main">Vertico spatially modulated illumination</span>

Vertico spatially modulated illumination (Vertico-SMI) is the fastest light microscope for the 3D analysis of complete cells in the nanometer range. It is based on two technologies developed in 1996, SMI and SPDM. The effective optical resolution of this optical nanoscope has reached the vicinity of 5 nm in 2D and 40 nm in 3D, greatly surpassing the λ/2 resolution limit applying to standard microscopy using transmission or reflection of natural light according to the Abbe resolution limit That limit had been determined by Ernst Abbe in 1873 and governs the achievable resolution limit of microscopes using conventional techniques.

<span class="mw-page-title-main">Research Institute of Molecular Pathology</span>

The Research Institute of Molecular Pathology (IMP) is a biomedical research center, which conducts curiosity-driven basic research in the molecular life sciences.

Super-resolution microscopy is a series of techniques in optical microscopy that allow such images to have resolutions higher than those imposed by the diffraction limit, which is due to the diffraction of light. Super-resolution imaging techniques rely on the near-field or on the far-field. Among techniques that rely on the latter are those that improve the resolution only modestly beyond the diffraction-limit, such as confocal microscopy with closed pinhole or aided by computational methods such as deconvolution or detector-based pixel reassignment, the 4Pi microscope, and structured-illumination microscopy technologies such as SIM and SMI.

Photo-activated localization microscopy and stochastic optical reconstruction microscopy (STORM) are widefield fluorescence microscopy imaging methods that allow obtaining images with a resolution beyond the diffraction limit. The methods were proposed in 2006 in the wake of a general emergence of optical super-resolution microscopy methods, and were featured as Methods of the Year for 2008 by the Nature Methods journal. The development of PALM as a targeted biophysical imaging method was largely prompted by the discovery of new species and the engineering of mutants of fluorescent proteins displaying a controllable photochromism, such as photo-activatible GFP. However, the concomitant development of STORM, sharing the same fundamental principle, originally made use of paired cyanine dyes. One molecule of the pair, when excited near its absorption maximum, serves to reactivate the other molecule to the fluorescent state.

<span class="mw-page-title-main">Eric Betzig</span> American physicist

Robert Eric Betzig is an American physicist who works as a professor of physics and professor of molecular and cell biology at the University of California, Berkeley. He is also a senior fellow at the Janelia Farm Research Campus in Ashburn, Virginia.

Three-photon microscopy (3PEF) is a high-resolution fluorescence microscopy based on nonlinear excitation effect. Different from two-photon excitation microscopy, it uses three exciting photons. It typically uses 1300 nm or longer wavelength lasers to excite the fluorescent dyes with three simultaneously absorbed photons. The fluorescent dyes then emit one photon whose energy is three times the energy of each incident photon. Compared to two-photon microscopy, three-photon microscopy reduces the fluorescence away from the focal plane by , which is much faster than that of two-photon microscopy by . In addition, three-photon microscopy employs near-infrared light with less tissue scattering effect. This causes three-photon microscopy to have higher resolution than conventional microscopy.

Gerd Ulrich "Uli" Nienhaus is a German physicist who is a professor and director of the Institute of Applied Physics, Karlsruhe Institute of Technology (KIT). At the KIT, he is also affiliated with the Institute of Nanotechnology, Institute of Biological and Chemical Systems, and Institute of Physical Chemistry, and he is an adjunct professor at the University of Illinois at Urbana-Champaign.

Ilaria Testa is an Italian-born scientist who is a Fellow at the SciLifeLab in Stockholm and an Associate Professor at the Department of Applied Physics at the School of Engineering Science at the KTH Royal Institute of Technology. She has made major contributions to advanced microscopy, particularly superresolution microscopy.

MINFLUX, or minimal fluorescence photon fluxes microscopy, is a super-resolution light microscopy method that images and tracks objects in two and three dimensions with single-digit nanometer resolution.

References

  1. "Francisco Balzarotti's lab at the IMP" . Retrieved 2023-07-19.
  2. https://www.linkedin.com/in/francisco-balzarotti/
  3. "Francisco Balzarotti | Light-based microscopy | Research Institute of Molecular Pathology (IMP)".
  4. "Stefan Hell".
  5. "Researchers achieve ultimate resolution limit in fluorescence microscopy".
  6. Balzarotti, Francisco; Eilers, Yvan; Gwosch, Klaus C.; Gynnå, Arvid H.; Westphal, Volker; Stefani, Fernando D.; Elf, Johan; Hell, Stefan W. (2017). "Nanometer resolution imaging and tracking of fluorescent molecules with minimal photon fluxes". Science. 355 (6325): 606–612. arXiv: 1611.03401 . Bibcode:2017Sci...355..606B. doi:10.1126/science.aak9913. hdl:11858/00-001M-0000-002C-2D9A-4. PMID   28008086. S2CID   5418707.
  7. "First multimessenger observation of a neutron-star merger is Physics World 2017 Breakthrough of the Year". 11 December 2017.
  8. "Researchers achieve ultimate resolution limit in fluorescence microscopy".
  9. Eilers, Yvan; Ta, Haisen; Gwosch, Klaus C.; Balzarotti, Francisco; Hell, Stefan W. (2018). "MINFLUX monitors rapid molecular jumps with superior spatiotemporal resolution". Proceedings of the National Academy of Sciences. 115 (24): 6117–6122. doi: 10.1073/pnas.1801672115 . PMC   6004438 . PMID   29844182.
  10. Pape, Jasmin K.; Stephan, Till; Balzarotti, Francisco; Büchner, Rebecca; Lange, Felix; Riedel, Dietmar; Jakobs, Stefan; Hell, Stefan W. (2020). "Multicolor 3D MINFLUX nanoscopy of mitochondrial MICOS proteins". Proceedings of the National Academy of Sciences. 117 (34): 20607–20614. Bibcode:2020PNAS..11720607P. doi: 10.1073/pnas.2009364117 . PMC   7456099 . PMID   32788360.
  11. Gwosch, Klaus C.; Pape, Jasmin K.; Balzarotti, Francisco; Hoess, Philipp; Ellenberg, Jan; Ries, Jonas; Hell, Stefan W. (2020). "MINFLUX nanoscopy delivers 3D multicolor nanometer resolution in cells". Nature Methods. 17 (2): 217–224. doi:10.1038/s41592-019-0688-0. PMID   31932776. S2CID   256840140.
  12. "Francisco Balzarotti | Light-based microscopy | Research Institute of Molecular Pathology (IMP)".
  13. https://www.balzarotti-lab.org/
  14. "Francisco Balzarotti | Research at a molecular biology institute when you are not a biologist". YouTube .
  15. "Seeing is Believing: Imaging the Molecular Processes of Life – Course and Conference Office".
  16. "Program".
  17. https://smlms.org/
  18. "ERC Starting Grants 2019 – List of Principal Investigators" (PDF). Retrieved 2023-07-19.
  19. "High-throughput 4D imaging for nanoscale cellular studies" . Retrieved 2023-07-19.