Superresolution Fluorescence Microscopy (nanoscopy)

Biomedical Applications

Publication list Christoph Cremer (1972 – 2016)

*In this publication list, the term superresolution microscopy (nanoscopy) is taken in its general meaning to cover all far field fluorescence microscopy methods enhancing the optical or structural resolution beyond the limits stated by Abbe (1873) and Rayleigh (1896) to be ca. 200 nm.

 

 

U. Birk, C. Cremer (2016) Perspectives in Super Resolved Fluorescence Microscopy:What Comes Next? Frontiers in Physics 4: Article11. doi: 10.3389/fphy.2016.00011.

 

F. Moser, G. Hildenbrand, P. Mueller, A. Al Saroori, A. Biswas, M.  Bach, F. Wenz, C. Cremer, N. Burger, M. R. Veldwijk, M. Hausmann (2016) Cellular Uptake of Gold Nanoparticles and Their Behavior as Labels for Localization Microscopy. Biophys. J., 110: 947 – 953.

 

A.Pierzyńska-Mach, A. Szczurek, F. Cella Zanacchi, F. Pennacchietti, J. Drukała, A. Diaspro, C. Cremer, Z. Darzynkiewicz, J. W. Dobrucki (2016) Subnuclear localization, rates and effectiveness of UVC-induced unscheduled DNA synthesis visualized by fluorescence widefield, confocal and super-resolution microscopy. Cell Cycle 15: 1156-1167.

 

I.Kirmes, A. Szczurek, K. Prakash, I. Charapits a,, C. Heiser, M. Musheev, F. Schock, K. Fornalczyk, D. Ma, U. Birk, C. Cremer, G. Reid (2015) A transient ischemic environment induces reversible compaction of chromatin. Genome Biology 16: 246 (pp. 1-19), doi: 10.1186/s13059-015-0802-2.

 

M. Stuhlmüller, J. Schwarz-Finsterle, E. Fey, J. Lux, M. Bach, C. Cremer, K. Hinderhofer, M. Hausmann, G. Hildenbrand (2015) In situ optical sequencing and structure analysis of a trinucleotide repeat genome region by localization microscopy after specific COMBO-FISH nano-probing. Nanoscale 7(42):17938-46.

 

O. Oleksiuk, M. Abba, K. C. Tezcan,W. Schaufler, F. Bestvater, N. Patil, M. Hafner, P. Altevogt, C. Cremer, H. Allgayer (2015) Single-Molecule Localization Microscopy allows for the analysis of cancer metastasis-specific miRNA distribution on the nanoscale, Oncotarget 29: 44745-57.

 

A. T. Szczurek, K. Prakash, H. K. Lee, D. J. Żurek-Biesiada, G. Best, M. Hagmann, J. W. Dobrucki, C. Cremer, U. Birk (2014) Single molecule localization microscopy of the distribution of chromatin using Hoechst and DAPI fluorescent probes. Nucleus 5 (4)1-10.

 

Q. Wang, R. Dierkes, R. Kaufmann, C. Cremer (2014) Quantitative analysis of individual Hepatocyte Growth Factor Receptor Clusters in Influenza A virus infected human epithelial cells using localization microscopy, Biochimica et Biophysica Acta 1838: 1191–1198.

 

C. Cremer, R. Kaufmann, M. Gunkel, F. Polanski, P. Müller, R. Dierkes, S. Degenhard, C. Wege, M. Hausmann, U. Birk (2014) Application Perspectives of localization microscopy in Virology. Histochem. Cell. Biol., DOI 10.1007/s00418-014-1203-4.

 

P. Müller,  N. A. Lemmermann ,· R. Kaufmann ,  M. Gunkel, D. Paech · G. Hildenbrand , R. Holtappels, C. Cremer, M. Hausmann (2014) Spatial distribution and structural arrangement of a murine cytomegalovirus glycoprotein detected by SPDM localization microscopy. Histochem Cell Biol DOI 10.1007/s00418-014-1185-2

 

C. Cremer (2014) Farfield Light Microscopy, Encyclopedia of Life Sciences (eLS), in press (Wiley-Blackwell). DOI:10.1002/9780470015902.a0005922.pub2.

 

C. Cremer (20149 Vorstoss in atomare Dimensionen. Laborjournal 7-8/2014: 65 – 67.

 

S. Rossberger, G. Best, D. Baddeley, R. Heintzmann, U. Birk, S. Dithmar, C. Cremer (2013) Combination of structured illumination and single molecule localization microscopy in one setup, J. Opt. 15, doi:10.1088/2040-8978/15/9/094003.

 

C. Cremer, B.R. Masters (2013) Resolution enhancement techniques in microscopy.

Eur. Phys. J. H, Eur. Phys. J. H 38: 281–344.

 

S. Rossberger, T. Ach, G. Best, C. Cremer, R. Heintzmann, S. Dithmar (2013) High resolution imaging of autofluorescent particles within drusen using structured illumination microscopy, British Journal of Ophthalmology 97 (4): 518 – 523.

 

G. Best, R. Amberger, C. Cremer (2013) Super-Resolution Microscopy: Interference and Pattern Techniques. In:  Fluorescence Microscopy: From Principles to Biological Applications Kubitschek U,Ed.), pp. 345 – 374. Wiley-Blackwell.

 

C. Cremer, Optics far Beyond the Diffraction Limit: From Focused Nanoscopy to Spectrally Assigned Localization Microscopy (2012). In:  Springer Handbook of Lasers and Optics, 2nd edition (F. Träger, Edit.), pp. 1351 – 1389.

 

R. Kaufmann, J. Piontek, F. Grüll, M. Kirchgessner, J.Rossa, H. Wolburg, I. E. Blasig, C. Cremer (2012) Visualization and quantitative analysis of reconstituted tight junctions using localization microscopy,  PLoS One 7 (2 ) e31128: 1 – 9.

 

O. Huber, A. Brunner, P. Maier, R. Kaufmann, P.-O. Couraud, C. Cremer, G. Fricker (2012) Localization microscopy (SPDM) reveals clustered formations of P-Glycoprotein in a human blood-brain barrier model, PLoS ONE 7 (9) e44776: 1-10.

 

R. Kaufmann, C. Cremer, J. G. Gall (2012) Superresolution imaging of transcription units on newt lampbrush chromosomes, Chromosome Research, DOI 10.1007/s10577-012-9306-z-

 

T. Ach, G. Best, S. Rossberger, R. Heintzmann, C. Cremer, S. Dithmar (2012)

Autofluorescence imaging of human RPE cell granules using structured illumination microscopy, Br. J. Ophthalmology, DOI 10.1136/bjophthalmol-2012-301547

 

T. Cremer T, Y. Markaki Y, B. Hübner B, A. Zunhammer A,  H. Strickfaden H, S. Beichmanis S, M. Heß M, L. Schermelleh L, M. Cremer, C.Cremer C (2012) Chromosome Territory Organization within the Nucleus. Encyclopedia of Molecular Cell Biology and Molecular Medicine,  DOI: 10.1002/3527600906.mcb.200300046.pub2.

 

D. Baddeley, D. Crossman, S. Rossberger, J. E. Cheyne, J. M. Montgomery, I. D. Jayasinghe, C. Cremer, M. B. Cannell, C. Soeller (2011) 4D Super-Resolution Microscopy with Conventional Fluorophores and Single Wavelength Excitation in

Optically Thick Cells and Tissues, PLoS ONE 6(5): e20645. doi:10.1371/journal.pone.0020645.

 

R. Kaufmann, P. Müller, G.L. Hildenbrand, M. Hausmann, C. Cremer (2011) Analysis of Her2/neu membrane protein clusters in breast cancer cells using localisation microscop, J. of Microscopy 242: 46–54.

 

Y. Weiland, P. Lemmer, C. Cremer  (2011) Combining FISH with Localisation Microscopy, Superresolution Imaging of Nuclear Genome Nanostructures, Chromosome Research  19: 5 – 23.

 

A.Brunner, G. Best, R. Amberger, P. Lemmer, T. Ach, S. Dithmar, R. Heintzmann, C. Cremer, Fluorescence Microscopy with Structured Excitation Illumination (2011). In: Handbook of Biomedical Optics (D.A Boas, C. Pitris, N. Ramanujam, Edits.), pp. 543 – 560.CRC Press, Taylor&Francis.

 

C. 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 (SPDM), Biotechnology Journal 6: 1037 – 1051.

 

G. Best, R. Amberger, D. Baddeley, T. Ach, S. Dithmar, R. Heintzmann, C. Cremer (2011) Structured illumination microscopy of autofluorescent aggregations in human  tissue, Micron 42: 330 – 335.

 

R. Kaufmann, P. Müller, M. Hausmann, C. Cremer (2011) Imaging label-free intracellular structures by localisation microscopy Micron 42: 348 – 352.

 

C. Cremer, Lichtmikroskopie unterhalb des Abbe-Limits (2011) Physik in Unserer Zeit 42: 21 – 29.

 

C. Cremer, Mikroskope und Mikroben. In: Viren und andere Mikroben: Heil oder Plage? Zum hundertsten Todestag von Robert Koch (Karlheinz Sonntag, Hg.). Studium Generale der Universität Heidelberg 2010. Universitätsverlag Winter, Heidelberg (2011).

 

Y. Markaki, M. Gunkel, L. Schermelleh, S. Beichmanis, J. Neumann,M. Heidemann, H. Leonhardt, D. Eick, C. Cremer, T. Cremer (2010) Functional nuclear organization of transcription and DNA replication: a topographical marriage between chromatin domains and the interchromatin compartment, Cold Spring Harbor Symposia on Quantitative Biology 75: 475 - 492

 

D. Hübschmann, N. Kepper, C. Cremer, G. Kreth (2010) Quantitative Approaches to Nuclear Architecture Analysis and Modelling, in: N.M. Adams and P.S. Freemont (eds.), Advances in Nuclear Architecture, 87 – 129. DOI 10.1007/978-90-481-9899-3_3, Springer Inc.

 

C. Grossmann, J. Schwarz-Finsterle, E. Schmitt, U. Birk, G. Hildenbrand, C. Cremer, L. Trakhtenbrot, and M. Hausmann Variations of the spatial fluorescence distribution in ABL gene chromatin domains measured in blood cell nuclei by SMI microscopy after COMBO – FISH labelling (2010). In: Microscopy - Science, Technology, Applications and Education (A. Méndez-Vilas and J. Díaz (Eds.), pp. 688 – 695. FORMATEX 2010.

 

M. Bohn, P.  Diesinger, R.  Kaufmann , Y. Weiland, P. Müller, M. Gunkel, A. von Ketteler, P. Lemmer , M. Hausmann, C. Cremer (2010) Localization microscopy reveals expression dependent parameters of chromatin nanostructure. Biophys. J. 99: 1358 – 1367.

 

L.-O. Tykocinski,  A. Sinemus, E. Rezavandy, Y. Weiland, D. Baddeley, C. Cremer, S. Sonntag, K. Willeke, J. Derbinski,  B. Kyewski (2010) Epigenetic regulation of promiscuous gene expression in thymic medullary epithelial cells. Proc. Natl. Acad. Scie. USA  107 (45): 19426–19431.

 

D. Baddeley, V.O. Chagin, L. Schermelleh, S. Martin, A. Pombo, P.M. Carlton, A. Gahl, P. Domaing, U. Birk, H. Leonhardt, C. Cremer, M.C. Cardoso (2010) Measurement of replication structures at the nanometer scale using super-resolution light microscopy. Nucleic Acids Res 38: e8 1-11. doi:10.1093/nar/gkp901.

 

M. Lang, T. Jegou, I. Chung, K. Richter, S. Münch, A. Udvarhelyi, C. Cremer, P. Hemmerich, J. Engelhardt, S. Hell, K. Rippe (2010). On the three-dimensional organization of promyelocytic leukemia nuclear bodies”, J. of Cell Science 123: 392 – 412.

 

C. Cremer, A. von Ketteler, P. Lemmer, R. Kaufmann, Y. Weiland, P. Mueller, M. Hausmann, D. Baddeley, A. Amberger (2010) Far field fluorescence microscopy of cellular structures @ molecular resolution, In: Nanoscopy and Multidimensional Optical Fluorescence Microscopy (A. Diaspro, Edit.), pp. 3/1 – 3/35. Taylor & Francis.

P. Müller, E. Schmitt, A. Jacob, J. Hoheisel, R. Kaufmann, C. Cremer, M. Hausmann (2010) COMBO-FISH Enables High Precision Localization Microscopy as a Prerequisite for Nanostructure Analysis of Genome Loci, Int. J. Mol. Sci. 11: 4094-4105.

T. Ach, G. Best, M. Ruppenstein. R. Amberger, C. Cremer, S. Diethmar (2010) Hochauflösende Fluoreszenzmikroskopie des Retinalen Pigmentepithels mittels strukturierter Beleuchtung. Der Ophtalmologe 11: 1037 – 1042.

 

M. Gunkel, F. Erdel, K. Rippe, P. Lemmer, R. Kaufmann, C. Hörmann, R. Amberger, C. Cremer (2009) Dual color localization microscopy of cellular nanostructures. Biotechnology J. 4: 927 – 938.

 

P. Lemmer, M. Gunkel, D. Baddeley, R. Kaufmann, Y. Weiland, P. Müller, A. Urich, R. Amberger, H. Eipel, M. Hausmann, C. Cremer (2009) Using Conventional Fluorescent Markers for Far-field Fluorescence Localization Nanoscopy allows Resolution in the 10 nm Regime,  J. of Microscopy 235: 163 – 171.

 

D. Baddeley, I.D. Jayasinghe, C. Cremer, M.B. Cannell, C. Soeller (2009) Light-induced dark states of organic fluorochromes enable 30 nm resolution imaging in standard media. Biophysical J. 96: L22-L24.

 

R. Kaufmann, P. Lemmer, M. Gunkel, Y. Weiland, P. Müller, M. Hausmann, D. Baddeley, R. Amberger, C. Cremer (2009)  SPDM – Single Molecule Superresolution of Cellular Nanostructures. Invited paper, Proc. SPIE 7185 :71850J-1 – 71850J-19. 

 

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. Applied Physics B 93: 1-12.

 

J. Reymann, D. Baddeley, P. Lemmer, W. Stadter, T. Jegou, K. Rippe, C. Cremer, U. Birk (2008) High precision structural analysis of subnuclear complexes in fixed and live cells via Spatially Modulated Illumination (SMI) microscopy. Chromosome Research 16: 367 –382.*

 

*First publication (March 2008) to demonstrate effective single molecule localization microscopy with single standard organic fluorphores and standard preparation conditions, together with a relevant biomedical application (nanoscopy of an important intracellular structure). Superresolution experiments performed in the C.Cremer Lab under the direct supervision of CC.

 

J. Rauch, T.A. Knoch, I. Solovei, K. Teller, S. Stein, K. Buiting, B. Horsthemke, J. Langowski, T. Cremer, M. Hausmann, C. Cremer (2008) Lightoptical precision measurements of the active and inactive Prader-Willi Syndrome imprinted regions in human cell nuclei. Differentiation 76: 66 – 83.

 

U.J. Birk, D. Baddeley, C. Cremer (2008) Nanosizing by spatially modulated illumination (SMI) microscopy and applications to the nucleus. In R. Hancock (ed) The Nucleus, Vol. 2: Chromatin, Transcription, Envelope, Proteins, Dynamics, and Imaging. DOI 10.1007/978-1-60327-461-6_21.

 

D. Baddeley, C. Batram, Y. Weiland, C. Cremer, U.J. Birk (2007) Nano-structure analysis using Spatially Modulated Illumination microscopy. Nature Protocols 2: 2640 – 2646.

 

H. Mathee, D. Baddeley, C. Wotzlaw, C. Cremer, U. Birk (2007) Spatially Modulated Illumination Microscopy using one objective lens. Optical Engineering, 46:  083603/1 – 083603/8.

 

S. Fenz, H. Mathee, G. Kreth, D. Baddeley, Y. Weiland, J. Schwarz-Finsterle, C.G. Cremer, U.J. Birk (2007) Two-color intranuclear distance measurements of gene regions in human lymphocytes. Proc. SPIE 6630: 663002-1 – 663002-10.

 

U. J. Birk, I. Upmann, D. Toomre, C. Wagner, C. Cremer (2007) Size Estimation of Protein Clusters in the Nanometer Range by Using Spatially Modulated Illumination Microscopy.

In:  Modern Research and Educational Topics in Microscopy (A. Mendez-Vilas, J. Diaz, Eds), Vol. 1, pp.272 – 279. FORMATEX Microscopy Series.

 

D. Baddeley, C. Carl, C. Cremer (2006) 4Pi microscopy deconvolution with a variable point-spread function. Appl. Opt. 45: 7056-7064.

 

C. Wagner, G. Hildenbrand, U. Spöri, C. Cremer (2006) Beyond nanosizing: an approach to shape analysis of fluorescent nanostructures by SMI-microscopy. Optik 117: 26–32.

 

U. J. Birk, D. Baddeley, C. Cremer (2006) Local Protein/Gene Density Measurements Using SMI Microscopy. Proc. SPIE 6188: 212-216.

 

C. Cremer and C. Cardoso (2006) Towards Cellular Imaging at Nanoscale. Imaging & Microscopy 8 (3): 20-21.

 

H. Mathée, D. Baddeley, C. Wotzlaw, J. Fandrey, C. Cremer, U. Birk (2006) Nanostructure of specific chromatin regions and nuclear complexes. Histochem. Cell Biology 125: 75-82.

 

G. Hildenbrand, A. Rapp, U. Spöri, C. Wagner, C. Cremer, M. Hausmann (2005) Nano-Sizing of Specific Gene Domains in Intact Human Cell Nuclei by Spatially Modulated Illumination Light Microscopy. Biophysical Journal 88: 4312–4318.

 

C. Wagner, U. Spöri, C. Cremer (2005) High-precision SMI microscopy size measurements by simultaneous frequency domain reconstruction of the axial point spread function, Optik 116: 15–21.

 

M. Hausmann, G. Hildenbrand, J. Schwarz-Finsterle, U. Birk, H. Schneider, C. Cremer, E. Schmitt (2005) New Technologies Measure Genome Domains. Biophotonics International October 2005: 34 - 36.

 

A. Schweitzer, C. Wagner, C. Cremer (2004) The nanosizing of fluorescent objects by 458 nm spatially modulated illumination microscopy using a simplified size evaluation algorithm. J. Phys. Condens. Matter 16: 2393–2404.

 

U. Spöri, A. V. Failla, C. Cremer (2004) Superresolution size determination in fluorescence microscopy: A comparison between spatially modulated illumination and confocal laser scanning microscopy. Journal of Applied Physics 95: 8436-8443.

 

S. Martin, A. V. Failla, U. Spoeri, C. Cremer and A. Pombo (2004) Measuring the Size of Biological Nanostructures with Spatially Modulated Illumination Microscopy. Molecular Biology of the Cell 15: 2449–2455.

 

C. Cremer (2003) Far Field Light Microscopy. In: Nature Encyclopedia of the Human Genome, Nature Publ. Group. DOI: 10.1038/npg.els.0005922

 

A. V. Failla, B. Albrecht, U. Spoeri, A. Schweitzer, A. Kroll, M. Bach, C. Cremer (2003) Nanotopology analysis using spatially modulated illumination (SMI) microscopy. Complexus 1: 29 – 40.

 

R. Heintzmann, Th. M. Jovin, Ch. Cremer (2002) Saturated patterned excitation microscopy – a concept for optical resolution improvement, J. Opt. Soc. Am. A 19: 1599-1609.*

*First publication to show the conceptual possibility that saturated excitation microscopy can overcome the Abbe limit in a similarly  radical way as STED.

 

B. Albrecht, A. Schweitzer, A.V. Failla, P. Edelmann, C.Cremer (2002) Spatially modulated illumination (SMI)  microscopy allows axial distance resolution in the nanometer range. Applied Optics 41: 80 - 87.

 

A.V. Failla, A. Cavallo, C. Cremer (2002) Subwavelength size determination using SMI virtual microscopy. Appl. Optics Vol. 41: 6651-6659.

 

A. V. Failla, B. Albrecht, U. Spoeri, A. Kroll, C. Cremer (2002) Nanosizing of fluorescent objects by spatially modulated illumination microscopy. Applied  Optics 41: 7275-7283.

 

R. Heintzmann, C.Cremer (2002) Axial tomographic confocal fluorescence microscopy. J. Microscopy 206: 7 – 23.

 

M. Heilemann, D.P. Herten, R. Heintzmann, C. Cremer, C. Müller, Ph. Tinnefeld, K.D. Weston, J. Wolfrum (2002) High-Resolution colocalization of single dye molecules by fluorescence lifetime imaging microscopy. Anal. Chemistry 74: 3511- 3517.*

*First experimental publication to show that the Abbe limit of optical resolution can be broken for single fluorescent molecules. A single molecule optical resolution of few tens of nm (~ 1/30 of the excitation wavelength) was demonstrated.

 

B. Albrecht, A.V. Failla, R. Heintzmann, C.Cremer (2001) Spatially modulated illumination microscopy: Online visualization of intensity distribution and prediction of nanometer precision of axial distance measurements by computer simulations. J. Biomed. Optics 6: 292 – 299.

 

A. Esa, A. E. Coleman, P. Edelmann, S. Silva, C. Cremer, S. Janz (2001) Conformational differences in the 3D-nanostructure of the immunoglobulin heavy-chain locus, a hotspot of chromosomal translocations in B lymphocytes. Cancer Genetics and Cytogenetics 127: 168 – 173.

 

B. Albrecht, R. Heintzmann, C. Cremer (2001) Online Visualisation of Axial Intensity Distribution in Spatially Modulated Illumination Microscopy, Optical Diagnostics of Living Cells IV (Daniel L. Farkas, Robert C. Leif, Editors) Proc. SPIE  4260: 126-130.

 

A.V. Failla, C. Cremer (2001) Virtual Statially Modulated Illumination Microscopy Prediction of Axial Distance Measurement, Optical Diagnostics of Living Cells IV (Daniel L. Farkas, Robert C. Leif, Editors) Proc.  SPIE 4260: 120-125

 

A.Esa, P. Edelmann, L. Trakthenbrot, N. Amariglio, G. Rechavi, M. Hausmann, C. Cremer (2000) 3D-spectral precision distance microscopy (SPDM) of chromatin nanostructures after triple-colour labeling: a study of the BCR region on chromosome 22 and the Philadelphia chromosome. J. Microscopy 199: 96 – 105.*

*First experimental publication to demonstrate a fluorescence based far field optical resolution of an intracellular 3D structure in the few tens of nanometer range by using the localization microscopy concept, in addition  with the first proof of 3D optical resolution down to 50 nm, plus its application to an important medical problem (cancer related chromosome break points). Work performed in collaboration with  the Tel Hashomer Hospital, Tel. Aviv University.

 

R. Heintzmann, G. Kreth, C. Cremer (2000) Reconstruction of axial tomographic high resolution data from confocal fluorescence microscopy. A method for improving 3D FISH images. Analytical Cellular Pathology 20: 7 – 15.

 

P. Edelmann, C. Cremer (2000) Improvement of confocal spectral precision distance microscopy (SPDM).In „Optical Diagnostics of Living Cells“ III. (D.L. Farkas, R.C. Leif, Edts.) Proc. SPIE 3921: 313 – 320.

 

Schneider, B., Albrecht, B., Jaeckle, P., Neofotistos, D., Söding, S., Jäger, Th., Cremer, C. (2000) Nanolocalization measurements in spatially modulated illumination microscopy using two coherent illumination beams. In „Optical Diagnostics of Living Cells“ III (D. L. Farkas, R. C. Leif, Edits) Proc. SPIE 3921: 321 – 330.

 

J. Rauch, M. Hausmann, I. Solovei, B. Horsthemke, T. Cremer, C. Cremer (2000): Measurement of local chromatin compaction by Spectral Precision Distance microscopy. In: Laser Microscopy (Edits. H.J. Tanke, H. Schneckenburger), Proc. SPIE 4164: 1 – 9.

 

C. Cremer, P. Edelmann, H. Bornfleth, G. Kreth, H. Muench, H. Luz, M. Hausmann (1999) Principles of Spectral Precision Distance confocal microscopy for the analysis of molecular nuclear structure. In: Handbook of Computer Vision and Applications (ed. B. Jähne, H. Haußecker, P. Geißler), Ch. 41., Vol. 3, Academic Press San Diego, New York: 839-857.*

*First detailed description of the concept of fluorescence based localization microscopy with photostable fluorophors in the context of biomedical applications. The introduction starts with the words “Localization by light plays a fundamental role in many fields of science…”.

 

P. Edelmann, A. Esa, M. Hausmann, C. Cremer (1999) Confocal laser scanning microscopy: In situ determination of the confocal point-spread function and the chromatic shifts in intact cell nuclei. Optik 110: 194-198.

 

B. Schneider, I. Upmann, I. Kirsten, J. Bradl, M. Hausmann, C. Cremer (1999): A dual-laser, spatially modulated illumination fluorescence microscope. Microsc. & Anal. 57: 5-7.

 

S. Dietzel, K. Schiebel, G. Little, P. Edelmann, G. A. Rappold, R. Eils, C. Cremer & T. Cremer (1999): The 3D Positioning of ANT2 and ANT3 genes within female X-chromosome territories correlates with gene activity. Exp. Cell Res. 252: 363 – 375.

 

M. Hausmann, A. Esa, P. Edelmann, L. Trakhtenbrot, H. Bornfleth, B. Schneider, J. Bradl, I. Ben-Bassat, G. Rechavi, C. Cremer (1999): Advanced precision light microscopy for the analysis of 3D-nanostructures of chromatin breakpoint regions: Towards a structure-function relationship of the BCR-ABL region. NATO ASI Series (Editor: G. Horneck, Kluwer Academic Publ., Dordrecht) 55: 219-230.

 

R. Heintzmann, C. Cremer (1999) Lateral modulated excitation microscopy: Improve­ment of resolution by using a diffraction grating. Proc. SPIE 3568: 185-196.*

*First publication to show both theoretically and experimentally the possibility to obtain an enhanced resolution by fluorescence based structured illumination microscopy (cited in  the justification of the Nobel Commission for the award 2014 in Chemistry).

 

P. Edelmann, A. Esa, H. Bornfleth, R. Heintzmann, M. Hausmann, C. Cremer (1999) Correlation of chromatic shifts and focal depth in Spectral Precision Distance microscopy measured by micro axial tomography. Proc. SPIE 3568: 89-95.

 

C. Cremer, P. Edelmann, A. Esa, H. Bornfleth, B. Schneider, J. Bradl, B. Rinke, L. Trakhtenbrot, S. Dietzel, M. Hausmann, T. Cremer (1999) Spektrale Präzisionsdistanzmikroskopie in der Genomforschung. Z. Med. Physik 9: 14-20.

 

H. Bornfleth, K. Sätzler, R. Eils, C. Cremer (1998) High precision distance measurements and volume-conserving segmentation of objects near and below the resolution limit in three-dimensional confocal fluorescence microscopy. J. Microscopy 189: 118-136.

*First experimental publication to demonstrate the possibility to perform fluorescence based far field localization microscopy at physiological temperatures with photostable fluorophors (i.e. without photoswitching).

 

B. Schneider, J. Bradl, I. Kirsten, M. Hausmann, C. Cremer (1998) High precision localization of fluorescent targets in the nanometer range by spatially modulated excitation fluorescence microscopy. In: Fluorescence Microscopy and Fluorescent Probes (J. Slavik, Ed.), Vol. 2: 63-68, Plenum Press.

 

C. Cremer, M. Hausmann, J. Bradl, K. Rinke (1998) Method and devices for measuring distances between object structures [describes principles and methods of localization microscopy]. US Patent 6,424,421 B1, published  July 2, 1998.*

*Granted US patent with the first description of the concept of far field based  localization microscopy using photostable fluorphors (i.e. without photoswitching). Priority of invention: December 23, 1996.

 

R. Heintzmann, H. Münch, C. Cremer (1997) High-precision measurements in epifluorescent microscopy - simulation and experiment. Cell Vision 4: 252-253.

 

M. Hausmann, B. Schneider, J. Bradl, C. Cremer (1997) High-precision distance microscopy of 3D-nanostructures by a spatially modulated excitation fluorescence microscope. In: Optical Biopsies and Microscopic Techniques II (Edts Bigio IJ, Schneckenburger H, Slavik J, Svanberg K, Viallet PM), Proc. SPIE 3197: 217-222.

 

S. Lindek, C. Cremer, E. H. K. Stelzer (1996) Confocal theta fluorescence microscopy with annular apertures. Appl. Optics 35: 126-130.

 

J. Bradl, B. Rinke, B. Schneider, M. Hausmann, C. Cremer (1996) Improved resolution in "practical" light microscopy by means of a glass fibre 2pi-tilting device. Proc. SPIE 2628: 140-146.

 

J. Bradl, B. Rinke, B. Schneider, P. Edelmann, H. Krieger, M. Hausmann, C. Cremer (1996) Resolution improvement in 3D fluorescence microscopy by object tilting. Microsc. Anal. 11/96: 9-11.

 

J. Bradl, B. Rinke, A. Esa, P. Edelmann, H. Krieger, B. Schneider, M. Hausmann, C. Cremer (1996): Comparative study of three-dimensional localization accuracy in conventional, confocal laser scanning and axial tomographic fluorescence light microscopy. Proc. SPIE  2926: 201-206.

 

P. E. Hänninen, S. W. Hell, J. Salo, E. Soini, C. Cremer, (1995): Two-photon excitation 4Pi confocal microscope: Enhanced axial resolution microscope for biological research. Appl. Phys. Lett.  66: 1698-1700.*

*joint publication with Stefan Hell. Experimental realization of the first fluorescence superresolution microscope based on the focused nanoscopy concept.

 

M. Schrader, F. Meinecke, K. Bahlmann, M. Kroug, C. Cremer, E. Soini, S.W. Hell (1995): Monitoring the excited state of a dye in a microscope by stimulated emission. Bioimaging 3: 147 – 153.*

*First publication (together with Stefan Hell) of a functioning prototype of a STED microscope (Nobel Prize 2014 in Chemistry awarded to Stefan Hell for his development of STED microscopy).

 

E. H. K. Stelzer, C. Cremer, S. Lindek (1995): Theory and Applications of Confocal Theta Microscopy. Zoological Studies 341 Suppl. I: 67-69.

 

J. Bradl, B. Schneider, B. Rinke, E. H. K. Stelzer, M. Durm, M. Hausmann, C. Cremer (1995): A versatile 2pi-tilting device for conventional light and confocal laser scanning microscopy. Zoological Studies (Taipeh) 34 Suppl. 1: 178-179.

 

S. Hell, S. Lindek, C. Cremer, E. H. K. Stelzer (1994): Measurement of the 4pi-confocal point spread function proves 75 nm axial resolution. Appl. Phys. Lett. 64: 1335-1337.*

 

*First proof-of-principle publication demonstrating enhanced (axial) resolution by focused nanoscopy.

 

S. W. Hell, E. H. K. Stelzer, S. Lindek, C. Cremer (1994): Confocal microscopy with an increased detection aperture: true-B 4Pi confocal microscopy. Optics Lett. 19: 222-224.*

 

*Early joint publication with Stefan Hell on an aspect of superresolution by focused nanoscopy.

 

S. Lindek, N. Salmon, C. Cremer, E. H. K. Stelzer (1994): Theta microscopy allows phase regulation in 4Pi(A)-confocal two-photon fluorescence microscopy. Optik 98: 15-20.

 

*Early joint publication with Stefan Hell on an aspect of superresolution by focused nanoscopy.

 

J. Bradl, M. Hausmann, B. Schneider, B. Rinke, C. Cremer (1994): A versatile 2pi-tilting device for fluorescence microscopes. J. Microscopy 176: 211-221.

 

C. Cremer, T. Cremer (1978): Considerations on a Laser-Scanning-Microscope with high resolution and depth of field. Microscopica  Acta 81: 31 – 44.*

 

*First publication to discuss in detail the construction of a laser scanning fluorescence microscope, and to propose the concept of a superresolving confocal 4Pi microscope (“focused nanoscopy”). This publication was cited by the Nobel Commission (Chemistry Award 2014) as the very first paper relevant to superresolution fluorescence microscopy.

 

C.Cremer, T. Cremer (1972): Verfahren zur Darstellung bzw. Modifikation von Objekt-Details, deren Abmessungen außerhalb der sichtbaren Wellenlängen  liegen. [describes principles of superresolution by 4pi based focused nanoscopy]. Deutsches Patentamt, Offenlegungsschrift DE 2116521(published October 12, 1972) [http://depatisnet.dpma.de/DepatisNet/depatisnet?window=1&space=menu&content=treffer&action=pdf&docid=DE000002116521A].*

 

*First ideas to overcome the optical resolution limit by a 4Pi microscopy approach, and to use photoswitchable molecules in connection  with the 4Pi  analysis of optical structures.