Christoph Cremer (born in Freiburg im Breisgau, Germany) is a German physicist and emeritus at Heidelberg University, former honorary professor at the University of Mainz Honorary Professorship for IMB's Christoph CremerLecturers at the Faculty of Physics, Johann Gutenberg University Mainz https://www.iph.uni-mainz.de/lehrende/ and was a former group leader at Institute of Molecular Biology (IMB) at the University of Mainz, Germany,Optics IMB Mainz, The Cremer Lab https://www.optics.imb-mainz.de/ who has successfully overcome the conventional limit of resolution that applies to light based investigations (the Abbe limit) by a range of different methods (1971/1978 development of the concept of 4Pi-microscopy; 1996 localization microscopy SPDM; 1997 spatially structured illumination SIM (first developed in 1995 by John M. Guerra at Polaroid Corp.)).https://www.imb.de/research-at-imb/cremer/research/ In the meantime, according to his own statement, Christoph Cremer is a member of the Max Planck Institute for Chemistry (Otto Hahn Institute) and the Max Planck Institute for Polymer Research.Dr. Christoph Cremer | Max Planck Institute for Polymer Research, Germany | STEM | COP April 2021 https://www.youtube.com/watch?v=L0EMIQzyIAE ORCHID Connecting Research & Researches, Christoph Cremer biography https://orcid.org/0000-0002-2090-6905 Royal Microscopy Society 2021 events https://www.rms.org.uk/rms-event-calendar/2021-events/imaging-oneworld-spatially-modulated-illumination.html
His actual microscope Vertico-SMI is the world's fastest nano light microscope that allows large scale investigation of supramolecular complexes including living cell conditions. It allows 3 D imaging of biological preparations marked with conventional fluorescent dyes and reaches a resolution of 10 nm in 2D and 40 nm in 3D.
This nanoscope has therefore the potential to add substantially to the current revolution in optical imaging which will affect the entire molecular biology, medical and pharmaceutical research. The technology allows the development of new strategies for the prevention, the lowering of risk and therapeutic treatment of diseases.
Biography Following a few semesters studying philosophy and history at the University of Freiburg and LMU Munich, Cremer studied physics in Munich (with financial support from the Studienstiftung des Deutschen Volkes) and completed his Ph.D. in genetics and biophysics in Freiburg. This was followed by post-doctoral studies at the Institute for Human Genetics at the University of Freiburg, several years in the United States at the University of California, and his "Habilitation" in general human genetics and experimental cytogenetics at the University of Freiburg. From 1983 until his retirement, he was teaching as a professor (chair since 2004) for "applied optics and information processing" at the Kirchhoff Institute for Physics at Heidelberg University. In addition, he was a member of the Interdisciplinary Center for Scientific Computing. Cremer was a participant in three "Projects of Excellence" of Heidelberg University (2007–2012), and was also a partner in the Biotechnology Cluster for cell-based and molecular medicine, one of five clusters selected in 2008 as German BMBF Clusters of Excellence. Elected as Second Speaker of the Senate of Heidelberg University, Cremer was also involved in university governance and politics. In his function as adjunct professor at the University of Maine and as member of the Jackson Laboratory (Bar Harbor, Maine), where he undertakes research for several weeks each year during the semester breaks, he was involved in the establishment of the biophysics center (Institute for Molecular Biophysics), which is linked with Heidelberg University through a "Global Network" collaboration.
Cremer is married to architect and artist Letizia Mancino-Cremer.
Fundamental developments
Developing the concept of 4Pi microscopy Cremer was involved early in the further development of laser based light microscopy approaches. First ideas had their origin in his graduate student years in the 1970s. Jointly with his brother Thomas Cremer, now professor (chair) of Anthropology and Human Genetics at LMU Munich, Christoph Cremer proposed the development of a hologram-based laser scanning 4Pi microscope. The basic idea was to focus laser light from all sides (space angle 4Pi) in a spot with a diameter smaller than the conventional laser focus and to scan the object by means of this spot. In this manner, it should be possible to achieve an improved optical resolution beyond the conventional limit of approx. 200 nm lateral, 600 nm axial.C. Cremer and T. Cremer (1978): Considerations on a laser-scanning-microscope with high resolution and depth of field Microscopica Acta VOL. 81 NUMBER 1 September, pp. 31—44 (1978) However the publication from 1978 C. Cremer and T. Cremer (1978): Considerations on a laser-scanning-microscope with high resolution and depth of field Microscopica Acta VOL. 81 NUMBER 1 September, pp. 31—44 (1978) had drawn an improper physical conclusion (i.e. a point-like spot of light) and had completely missed the axial resolution increase as the actual benefit of adding the other side of the solid angle.The Nobel Prize in Chemistry 2014 https://www.nobelprize.org/prizes/chemistry/2014/hell/biographical/ Since 1992, 4Pi microscopy developed by Stefan Hell (Max-Planck Institute for Biophysical Chemistry, Göttingen) into a highly efficient, high-resolution imaging process, using two microscope objective lenses of high numeric aperture opposing each other.
Development of the first DNA laser-UV-microirradiation technique for living cells In the early 1970s, the brothers realized a UV laser micro irradiation instrument which for the first time made it possible to irradiate in a controlled manner only a tiny part of a living cell at the absorption maximum for DNA (257 nm). This replaced the conventional UV partial irradiation practiced for over 60 years. In this way, it was possible for the first time to induce alterations in the DNA in a focused manner (i.e. at predetermined places in the cell nucleus of living cells) without compromising the cells ability to divide and to survive. Specific very small cell regions could be irradiated and thus the dynamics of macromolecules (DNA) contained there quantitatively estimated. Furthermore, due to the high speed of the process using irradiation times of fractions of a second, it became possible to irradiate even moving cell organelles. This development provided the basis for important experiments in the area of genome structure research (establishing the existence of so-called chromosome territories in living mammalian cells) and led, a few years later (1979/1980) to a successful collaboration with the biologist Christiane Nüsslein-Volhard (Max Planck Institute for Developmental Biology, Tübingen). In this collaboration Cremer used his UV laser micro irradiation equipment to elicit cellular changes in the early larval stages of the fruit fly Drosophila melanogaster.
Development of the confocal laser scanning microscopy for fluorescence On the basis of experience gained in the construction and application of the UV laser micro irradiation instrument, the Cremer brothers designed in 1978 a laser scanning process which scans point-by-point the three-dimensional surface of an object by means of a focused laser beam and creates the over-all picture by electronic means similar to those used in scanning electron microscopes. It is this plan for the construction of a confocal laser scanning microscope (CSLM), which for the first time combined the laser scanning method with the 3D detection of biological objects labeled with fluorescent markers that earned Cremer his professorial position at Heidelberg University. During the next decade, the confocal fluorescence microscopy was developed into a technically fully matured state in particular by groups working at the University of Amsterdam and the European Molecular Biology Laboratory (EMBL) in Heidelberg and their industry partners. In later years, this technology was adopted widely by biomolecular and biomedical laboratories and remains to this day the gold standard as far as three-dimensional light microscopy with conventional resolution is concerned.
Development of the super resolution microscopy methods
The goal of microscopy is in many cases to determine the size of individual, small objects. Conventional fluorescence microscopy can only establish sizes to around the conventional optical resolution limit of approximately 200 nm (lateral). More than 20 years after submitting the 4 pi patent application,Cremer C, Cremer T (1971) Punkthologramme: Physikalische Grundlagen und mögliche Anwendungen. Enclosure to Patent application DE 2116521 "Verfahren zur Darstellung bzw. Modifikation von Objekt-Details, deren Abmessungen außerhalb der sichtbaren Wellenlängen liegen" (Procedure for the imaging and modification of object details with dimensions beyond the visible wavelengths). Filed 5 April 1971; publication date 12 October 1972.Deutsches Patentamt, Berlin. http://depatisnet.dpma.de/DepatisNet/depatisnet?action=pdf&docid=DE000002116521A Christoph Cremer returned to the problem of the diffraction limit. With the Vertico SMI microscope he could realize his various super resolution techniques including SMI, SPDM, SPDMphymod and LIMON. These methods are mainly used for biomedical applications
Spatially Modulated Illumination SMI Around 1995, he commenced with the development of a light microscopic process, which achieved a substantially improved size resolution of cellular nanostructures stained with a fluorescent marker. This time he employed the principle of wide field microscopy combined with structured laser illumination (spatially modulated illumination, SMI)US patent 7,342,717, filed 10 July 1997: Christoph Cremer, Michael Hausmann, Joachim Bradl, Bernhard Schneider Wave field microscope with detection point spread function Currently, a size resolution of 30 – 40 nm (approximately 1/16 – 1/13 of the wavelength used) is being achieved. In addition, this technology is no longer subjected to the speed limitations of the focusing microscopy so that it becomes possible to undertake 3D analyses of whole cells within short observation times (at the moment around a few seconds). Disambiguation SMI: S = spatially, M = Modulated I= Illumination.
Localization Microscopy SPDM Also around 1995, Cremer developed and realized new fluorescence based wide field microscopy approaches which had as their goal the improvement of the effective optical resolution (in terms of the smallest detectable distance between two localized objects) down to a fraction of the conventional resolution (spectral precision distance/position determination microscopy, SPDM; Disambiguation SPDM: S = Spectral, P = Precision, D = Distance, M = Microscopy).US patent 6,424,421, filed 23 December 1996: Christoph Cremer, Michael Hausmann, Joachim Bradl, Bernd Rinke Method and devices for measuring distances between object structures
Localization Microscopy SPDMphymod With this method, it is possible to use conventional, well established and inexpensive fluorescent dyes, standard like GFP, RFP, YFP, Alexa 488, Alexa 568, Alexa 647, Cy2, Cy3, Atto 488 and fluorescein.