Christoph Cremer

Last updated

Christoph Cremer (born in Freiburg im Breisgau, Germany) is a German physicist and emeritus [1] at the Ruprecht-Karls-University Heidelberg, former honorary professor at the University of Mainz [2] [3] and was a former group leader at Institute of Molecular Biology (IMB) at the Johannes Gutenberg University of Mainz, Germany, [4] 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.) [5] ). [6] [7] 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. [8] [9] [10]

Contents

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 Freiburg University and Munich University, 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 Freiburg University, several years in the United States at the University of California, and his "Habilitation" in general human genetics and experimental cytogenetics at Freiburg University. 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 the University of Heidelberg. In addition, he was a member of the Interdisciplinary Center for Scientific Computing Cremer was a participant in three "Projects of Excellence" of the University of Heidelberg (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 the University of Heidelberg, 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 the University of Heidelberg 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 the Ludwigs-Maximilian University in 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. [11] [12] However the publication from 1978 [13] 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. [14] 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. [15] [16]

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). [17] 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 . [18] [19]

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. [11] 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 the University of Heidelberg. 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, [11] [20] 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 [21]

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) [22] [23] [24] 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. [25]

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). [26] [27] [28]

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. [29] [30] in contrast to other localization microscopy technologies that need two laser wavelengths when special photo-switchable/photo-activatable fluorescence molecules are used. A further example for the use of SPDMphymod is an analysis of Tobacco mosaic virus (TMV) particles. [31] [32] or virus–cell interaction. [33] [34]

Disambiguation SPDMphymod: S = Spectral, P = Precision D = Distance, M = Microscopy, phy = physically, mod = modifiable

3D Light microscopical nanosizing (LIMON) microscopy

Combining SPDM and SMI, known as LIMON microscopy. [30] Christoph Cremer can currently achieve a resolution of approx. 10 nm in 2D and 40 nm in 3D in wide field images of whole living cells. [35] Widefield 3D "nanoimages" of whole living cells currently still take about two minutes, but work to reduce this further is currently under way. Vertico-SMI is currently the fastest optical 3D nanoscope for the three-dimensional structural analysis of whole cells worldwide [24] As a biological application in the 3D dual color mode the spatial arrangements of Her2/neu and Her3 clusters was achieved. The positions in all three directions of the protein clusters could be determined with an accuracy of about 25 nm. [36]

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">Microscope</span> Scientific instrument

A microscope is a laboratory instrument used to examine objects that are too small to be seen by the naked eye. Microscopy is the science of investigating small objects and structures using a microscope. Microscopic means being invisible to the eye unless aided by a microscope.

<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.

<span class="mw-page-title-main">Diffraction-limited system</span> Optical system with resolution performance at the instruments theoretical limit

In optics, any optical instrument or system – a microscope, telescope, or camera – has a principal limit to its resolution due to the physics of diffraction. An optical instrument is said to be diffraction-limited if it has reached this limit of resolution performance. Other factors may affect an optical system's performance, such as lens imperfections or aberrations, but these are caused by errors in the manufacture or calculation of a lens, whereas the diffraction limit is the maximum resolution possible for a theoretically perfect, or ideal, optical system.

<span class="mw-page-title-main">X-ray microscope</span> Type of microscope that uses X-rays

An X-ray microscope uses electromagnetic radiation in the X-ray band to produce magnified images of objects. Since X-rays penetrate most objects, there is no need to specially prepare them for X-ray microscopy observations.

<span class="mw-page-title-main">Fluorescence microscope</span> Optical microscope that uses fluorescence and phosphorescence

A fluorescence microscope is an optical microscope that uses fluorescence instead of, or in addition to, scattering, reflection, and attenuation or absorption, to study the properties of organic or inorganic substances. "Fluorescence microscope" refers to any microscope that uses fluorescence to generate an image, whether it is a simple set up like an epifluorescence microscope or a more complicated design such as a confocal microscope, which uses optical sectioning to get better resolution of the fluorescence image.

<span class="mw-page-title-main">Confocal microscopy</span> Optical imaging technique

Confocal microscopy, most frequently confocal laser scanning microscopy (CLSM) or laser scanning confocal microscopy (LSCM), is an optical imaging technique for increasing optical resolution and contrast of a micrograph by means of using a spatial pinhole to block out-of-focus light in image formation. Capturing multiple two-dimensional images at different depths in a sample enables the reconstruction of three-dimensional structures within an object. This technique is used extensively in the scientific and industrial communities and typical applications are in life sciences, semiconductor inspection and materials science.

<span class="mw-page-title-main">Two-photon excitation microscopy</span> Fluorescence imaging technique

Two-photon excitation microscopy is a fluorescence imaging technique that is particularly well-suited to image scattering living tissue of up to about one millimeter in thickness. Unlike traditional fluorescence microscopy, where the excitation wavelength is shorter than the emission wavelength, two-photon excitation requires simultaneous excitation by two photons with longer wavelength than the emitted light. The laser is focused onto a specific location in the tissue and scanned across the sample to sequentially produce the image. Due to the non-linearity of two-photon excitation, mainly fluorophores in the micrometer-sized focus of the laser beam are excited, which results in the spatial resolution of the image. This contrasts with confocal microscopy, where the spatial resolution is produced by the interaction of excitation focus and the confined detection with a pinhole.

<span class="mw-page-title-main">Autofluorescence</span>

Autofluorescence is the natural emission of light by biological structures such as mitochondria and lysosomes when they have absorbed light, and is used to distinguish the light originating from artificially added fluorescent markers (fluorophores).

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.

Scanning confocal electron microscopy (SCEM) is an electron microscopy technique analogous to scanning confocal optical microscopy (SCOM). In this technique, the studied sample is illuminated by a focussed electron beam, as in other scanning microscopy techniques, such as scanning transmission electron microscopy or scanning electron microscopy. However, in SCEM, the collection optics are arranged symmetrically to the illumination optics to gather only the electrons that pass the beam focus. This results in superior depth resolution of the imaging. The technique is relatively new and is being actively developed.

<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">Raman microscope</span> Laser microscope used for Raman spectroscopy

The Raman microscope is a laser-based microscopic device used to perform Raman spectroscopy. The term MOLE is used to refer to the Raman-based microprobe. The technique used is named after C. V. Raman, who discovered the scattering properties in liquids.

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.

Nikon Instruments is a division of Nikon Corporation, which is headquartered in Tokyo. Its US operations are based in Melville, New York and its European operations in Amstelveen, Netherlands. Nikon Instruments is a specialist in optical instrumentation.

The technique of vibrational analysis with scanning probe microscopy allows probing vibrational properties of materials at the submicrometer scale, and even of individual molecules. This is accomplished by integrating scanning probe microscopy (SPM) and vibrational spectroscopy. This combination allows for much higher spatial resolution than can be achieved with conventional Raman/FTIR instrumentation. The technique is also nondestructive, requires non-extensive sample preparation, and provides more contrast such as intensity contrast, polarization contrast and wavelength contrast, as well as providing specific chemical information and topography images simultaneously.

Endomicroscopy is a technique for obtaining histology-like images from inside the human body in real-time, a process known as ‘optical biopsy’. It generally refers to fluorescence confocal microscopy, although multi-photon microscopy and optical coherence tomography have also been adapted for endoscopic use. Commercially available clinical and pre-clinical endomicroscopes can achieve a resolution on the order of a micrometre, have a field-of-view of several hundred μm, and are compatible with fluorophores which are excitable using 488 nm laser light. The main clinical applications are currently in imaging of the tumour margins of the brain and gastro-intestinal tract, particularly for the diagnosis and characterisation of Barrett’s Esophagus, pancreatic cysts and colorectal lesions. A number of pre-clinical and transnational applications have been developed for endomicroscopy as it enables researchers to perform live animal imaging. Major pre-clinical applications are in gastro-intestinal tract, toumour margin detection, uterine complications, ischaemia, live imaging of cartilage and tendon and organoid imaging.

Lattice light-sheet microscopy is a modified version of light sheet fluorescence microscopy that increases image acquisition speed while decreasing damage to cells caused by phototoxicity. This is achieved by using a structured light sheet to excite fluorescence in successive planes of a specimen, generating a time series of 3D images which can provide information about dynamic biological processes.

References

  1. ↑ "Department for Physics and Astronomy". www.physik.uni-heidelberg.de. Retrieved 22 December 2021.
  2. ↑ Honorary Professorship for IMB's Christoph Cremer
  3. ↑ Lecturers at the Faculty of Physics, Johann Gutenberg University Mainz https://www.iph.uni-mainz.de/lehrende/
  4. ↑ Optics IMB Mainz, The Cremer Lab https://www.optics.imb-mainz.de/
  5. ↑ Guerra, John M. (26 June 1995). "Super-resolution through illumination by diffraction-born evanescent waves". Applied Physics Letters. 66 (26): 3555–3557. Bibcode:1995ApPhL..66.3555G. doi:10.1063/1.113814. ISSN   0003-6951.
  6. ↑ "Super-Resolution Light Microscopy | Prof. Christoph Cremer | Light Optical Nanoscopy by Localization Microscopy and Structured Illumination". Archived from the original on 6 February 2020. Retrieved 1 October 2020.
  7. ↑ https://www.imb.de/research-at-imb/cremer/research/ [ dead link ]
  8. ↑ Dr. Christoph Cremer | Max Planck Institute for Polymer Research, Germany | STEM | COP April 2021 https://www.youtube.com/watch?v=L0EMIQzyIAE
  9. ↑ ORCHID Connecting Research & Researches, Christoph Cremer biography https://orcid.org/0000-0002-2090-6905
  10. ↑ Royal Microscopy Society 2021 events https://www.rms.org.uk/rms-event-calendar/2021-events/imaging-oneworld-spatially-modulated-illumination.html
  11. 1 2 3 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)
  12. ↑ Cremer, T.; Cremer, C. (2006). "Rise, fall and resurrection of chromosome territories: a historical perspective Part II. Fall and resurrection of CTs during the 1950th to 1980th. Part III. Chromosome territories and the functional nuclear architecture: experiments and models from the 1990th to the present. In". European Journal of Histochemistry. 50: 223–272.
  13. ↑ 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)
  14. ↑ The Nobel Prize in Chemistry 2014 https://www.nobelprize.org/prizes/chemistry/2014/hell/biographical/
  15. ↑ Hell, S.; Lindek, S.; Cremer, C.; Stelzer, E. H. K. (1994). "Measurement of the 4pi-confocal point spread function proves 75 nm axial resolution". Applied Physics Letters. 64 (11): 1335–1337. Bibcode:1994ApPhL..64.1335H. doi:10.1063/1.111926.
  16. ↑ Hänninen, P. E.; Hell, S. W.; Salo, J.; Soini, E.; Cremer, C. (1995). "Two-photon excitation 4Pi confocal microscope - Enhanced axial resolution microscope for biological research". Applied Physics Letters. 68 (13): 1698–1700. Bibcode:1995ApPhL..66.1698H. doi:10.1063/1.113897.
  17. ↑ Cremer, C.; Cremer, T. (1974). "An ultraviolet Laser microbeam for 257 nm/Eine Laser-UV-Mikrobestrahlungsapparatur für 257 nm". Microscopica Acta. 75 (4): 331–337.
  18. ↑ Lohs-Schardin, M.; Cremer, C.; Nüsslein-Volhard, C. (1979). "A Fate Map for the Larval Epidermis of Drosophila melanogaster: Localized Cuticle Defects Following Irradiation of the Blastoderm with an Ultraviolet Laser Microbeam". Developmental Biology. 73 (2): 239–255. doi:10.1016/0012-1606(79)90065-4. PMID   115734.
  19. ↑ Nüsslein-Volhard, C.; Lohs-Schardin, M.; Cremer, C. (1980). "A dorso-ventral shift of embryonic primordia in a new maternal-effect mutant of Drosophila". Nature. 283 (5746): 474–476. Bibcode:1980Natur.283..474N. doi:10.1038/283474a0. PMID   6766208. S2CID   4320963.
  20. ↑ 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
  21. ↑ "Biomedical applications for Super Resolution Microscopy". Archived from the original on 13 October 2016. Retrieved 13 October 2016.
  22. ↑ Heintzmann, R.; Cremer, C. (1999). "Lateral modulated excitation microscopy: Improvement of resolution by using a diffraction grating". Proc. SPIE. 3568: 185–196. Bibcode:1999SPIE.3568..185H. doi:10.1117/12.336833. S2CID   128763403.
  23. ↑ 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
  24. 1 2 Baddeley, D.; Batram, C.; Weiland, Y.; Cremer, C.; Birk, U.J. (2007). "Nano-structure analysis using Spatially Modulated Illumination microscopy". Nature Protocols. 2 (10): 2640–2646. doi:10.1038/nprot.2007.399. PMID   17948007. S2CID   22042676.
  25. ↑ Best, G; Amberger, R; Baddeley, D; Ach, T; Dithmar, S; Heintzmann, R; Cremer, C (2011). "Structured illumination microscopy of autofluorescent aggregations in human tissue". Micron. 42 (4): 330–335. doi:10.1016/j.micron.2010.06.016. PMID   20926302.
  26. ↑ Bradl, J.; Rinke, B.; Esa, A.; Edelmann, P.; Krieger, H.; Schneider, B.; Hausmann, M.; Cremer, C. (1996). Bigio, Irving J; Grundfest, Warren S; Schneckenburger, Herbert; Svanberg, Katarina; Viallet, Pierre M (eds.). "Comparative study of three-dimensional localization accuracy in conventional, confocal laser scanning and axialtomographic fluorescence light microscopy". Proc. SPIE. Optical Biopsies and Microscopic Techniques. 2926: 201–206. Bibcode:1996SPIE.2926..201B. doi:10.1117/12.260797. S2CID   55468495.
  27. ↑ 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
  28. ↑ Heintzmann, R.; Münch, H.; Cremer, C. (1997). "High-precision measurements in epifluorescent microscopy - simulation and experiment". Cell Vision. 4: 252–253.
  29. ↑ Manuel Gunkel, Fabian Erdel, Karsten Rippe, Paul Lemmer, Rainer Kaufmann, Christoph Hörmann, Roman Amberger and Christoph Cremer: Dual color localization microscopy of cellular nanostructures. In: Biotechnology Journal, 2009, 4, 927–938. ISSN 1860-6768
  30. 1 2 Reymann, J; Baddeley, D; Gunkel, M; Lemmer, P; Stadter, W; Jegou, T; Rippe, K; Cremer, C; Birk, U (May 2008). "High-precision structural analysis of subnuclear complexes in fixed and live cells via spatially modulated illumination (SMI) microscopy". Chromosome Research. 16 (3): 367–82. doi: 10.1007/s10577-008-1238-2 . PMID   18461478.
  31. ↑ Cremer, R. Kaufmann, M. Gunkel, S. Pres, Y. Weiland, P- Müller, T. Ruckelshausen, P. Lemmer, F. Geiger, S. Degenhard, C. Wege, N- A. W. Lemmermann, R. Holtappels, H. Strickfaden, M. Hausmann (2011): Superresolution imaging of biological nanostructures by spectral precision distance microscopy: Biotechnology 6: 1037–1051
  32. ↑ Manuel Gunkel, Fabian Erdel, Karsten Rippe, Paul Lemmer, Rainer Kaufmann, Christoph Hörmann, Roman Amberger and Christoph Cremer (2009): Dual color localization microscopy of cellular nanostructures. In: Biotechnology Journal, 2009, 4, 927–938. ISSN 1860-6768
  33. ↑ C. Cremer, R.Kaufmann, M. Gunkel, F. Polanski, P. Müller, R. Dierkes, S. Degenhard, C. Wege, M. Hausmann, U. Birk:"Application perspectives of localization microscopy in virology", Histochem Cell Biol (2014)
  34. ↑ Qiaoyun Wang, Rüdiger Dierkes, Rainer Kaufmanna, Christoph Cremer:"Quantitative analysis of individual hepatocyte growth factor receptor clusters in influenza A virus infected human epithelial cells using localization microscopy" Biochimica et Biophysica Acta (2014)
  35. ↑ P. Lemmer, M.Gunkel, D.Baddeley, R. Kaufmann, A. Urich, Y. Weiland, J.Reymann, P. Müller, M. Hausmann, C. Cremer(2008): SPDM – Light Microscopy with Single Molecule Resolution at the Nanoscale: in Applied Physics B, Vol 93, pp. 1-12
  36. ↑ Kaufmann, Rainer; Müller, Patrick; Hildenbrand, Georg; Hausmann, Michael; Cremer, Christoph (2010). "Analysis of Her2/neu membrane protein clusters in different types of breast cancer cells using localization microscopy". Journal of Microscopy. 242 (1): 46–54. doi:10.1111/j.1365-2818.2010.03436.x. PMID   21118230. S2CID   2119158.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.