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Researcher from Heidelberg Sets New Standard with the World’s Fastest Nano-microscope

29 10 2008
Professor Christoph Cremer following his break-through concept of the 4Pi microscopy in 1971 has now broken, for a second time in his research career, the limits of what can be achieved through lightoptical microscopy
“Very deep, very wide, in vivo and above all ultra rapid” is the headline description used by Professor Christoph Cremer, head of Applied Optics and Information Processing of the Kirchhoff Institute for Physics at Heidelberg University, when describing his optical nanoscope Vertico-SMI, which he intends to use to unravel the cell’s molecular mysteries.  Professor Christoph Cremer following his break-through concept of the 4Pi microscopy in 1971 has now broken, for a second time in his research career, the limits of what can be achieved  through lightoptical microscopy.

Prof. Cremer, who is one of the five winners in the German excellence-cluster competition with his stem-cell project in the biotech cluster “Cell-based and Molecular Medicine”, thus makes his contribution to the Initiative of Excellence of Heidelberg University.

“A combination of four decisive advantages places Cremer’s Nanoscope at the leading edge: firstly, the possibility of investigating large cellular areas with a spatial resolution of down to 10 nanometres; secondly, the unsurpassed recording and image processing speed, which, thirdly, makes it possible to take nano-images of whole living cells in 3D and in real time; fourthly, the option to use common fluorescent dyes. This offers ideal conditions for routine use”, says the Innovation Manager, Dr Andrea Nestl from the Technologie-Lizenz-Büro (TLB) GmbH, who is in charge of the commercialisation of this patent portfolio (Tel. +49 721 7900456,

This innovative and patented process which has a sensational spatial resolution of 10 nanometres in 2D and 40 nanometres in 3D 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.  The current prototype of Vertico-SMI even allows the investigation of living cell cultures in liquid media in petri dishes.  An incubation chamber provides full control over the gas atmosphere surrounding the sample.

Comparable nanoscopy methods such as the US developments PALM and SIM/OMX also use wide filed microscopy technologies but do not possess the exceptional recording speed so that it is not possible to take pictures of whole living cells with a high density of molecules. The STORM technology developed at Harvard, while fast, requires a pH value that damages living cells.  Focussing nanoscopy methods such as STED and ISOSTED are very useful in achieving rapid nanoimaging of small areas but for a large area, as is captured by widefield microscopy, these methods take too long because a large number of small areas have to be registered one after the other. 

Vertico-SMI is the only nanoscope world-wide that is capable of recording a 3D image of a whole living cell in a matter of two minutes.  The high resolution image is assembled by the computer from several thousand individual images.

The possible areas of application of such a rapid, easy to use and extremely robust optical nanoscope extend well beyond biomedical applications.  Applications in material research, quality control of nanolayers or in the area of electronics, in particular in high through-put processes, are likely candidates since even the tiniest deformation in 3D can be detected.

Vertico-SMI is the only nanoscope world-wide that is capable of recording a 3D image of a whole living cell in a matter of two minutes.  
The Vertico-SMI (design lower right) is the first optical nanoscope suitable for routine use that is sufficiently fast to observe whole living cells. It allows a wide panorama view (Image upper left) of fluorescent membrane proteins, combined with a sharp view into the depth. Its resolution is up to 20 times better than conventional light microscopy. Molecules with a distance of only 14 nanometres are clearly distinguishable (Image upper right, magnified detail of image left). The sensational 3D resolution of 50 nanometres shows green fluorescing membrane proteins of a human cancer cell (image lower left, recently published in: Applied Physics B).

Pushing the limits: As inventor, always at the leading edge

In his research career, Professor Christoph Cremer has combined in a unique manner findings in the fields of optical physics and molecular biology.  With the Vertico-SMI, he was successful in a highly innovative manner to push the boundaries of optical resolution.

Already in 1971, did he for the first time propose a method to overcome the optical resolution limit postulated in 1873 by Zeiss co-founder Ernst Abbe, when, together with his brother Professor Thomas Cremer (Ludwig-Maximilians-Universität München), he put forward the first concept of  4Pi microscopy (German Patent DE 2116521).

Professor Cremer’s development of the first Laser-UV-microirradiation technology for inducing targeted DNA damage in live cells allowed the analysis of spatial genome organization; other applications in the study of embryonic development led to a highly successful collaboration with the German Scientist Christine Nüsslein-Volhard, who later won the Nobel Prize.

The first detailed technical concept for the development of a confocal laser scanning microscope (CLSM) for the investigation of fluorescent labelled cellular structures – to be found today in almost every biological research institute – also has its origin with the two inventive brothers.

Professor C Cremer is a participant in three current Excellence Projects at Heidelberg University. Furthermore, in his position as Adjunct Professor at the US University of Maine, he participates in the establishment of a biophysical centre (Institute for Molecular Biophysics, IMB) at the renowned Jackson Laboratory.

[German version]

Contact details of Inventor:
Prof. Dr. Dr. Christoph Cremer
Professor (Chair) for Applied Optics and Information Processing, (KIP) / Kirchhoff Institute for Physics  & Director Biophysics of Genome Structure, Institute for Pharmacy and Molecular Biotechnology (IPMB),
Universität Heidelberg
Im Neuenheimer Feld 227
69120 Heidelberg
Tel. +49 6221 549252 (Administration Mrs. Dipl.-Phys. Bach: 549271), Fax +49 6221 549112

Contact for parties with an interest in the commercialisation of this technology:
Dr. Andrea Nestl, Innovation Management
Technologie-Lizenz-Büro (TLB) der baden-württembergischen Hochschulen GmbH
Ettlinger Straße 25
76137 Karlsruhe
Tel. +49 721 7900456, Fax +49 721 7900479

For queries from the media:
Dr. Michael Schwarz
Universität Heidelberg
Media Spokesperson
Grabengasse 1
69117 Heidelberg
Tel. +49 6221 542310, Fax +49 6221 542317
Editor: Email
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