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Molecular scale resolution possible with N-SIM microscopy system

Nikon Instruments is proud to announce that Nikon Corporation has signed an agreement with the University of California, San Francisco Office of Technology Management for Structured Illumination Microscopy (SIM) technology. Under the terms of the agreement, UCSF will license its technology to Nikon to make N-SIM enabled microscopes designed to realise resolution higher than can be achieved by conventional optical microscopes.

Optical microscopes are essential for the clear observation of tissues and cells in life science research. However, if multiple objects such as protein molecules cluster at distances of less than 200nm apart, conventional optical microscopes cannot identify them as single objects, necessitating the use of instrumentation such as electron microscopes. Nikon’s super resolution fluorescence microscopy technology greatly exceeds the resolution limits of conventional optical microscopes, making it possible to view microstructures and nanostructures of fixed and living cells with molecular-scale resolution.

Nikon’s N-SIM microscopy system can produce two times the resolution of conventional optical microscopes by combining SIM technology licensed from UCSF and based on the world renowned Eclipse Ti research inverted microscope with Nikon’s legendary CFI Apo TIRF 100x oil objective lens (N.A. 1.49), developed using unique optical technologies and manufacturing techniques. The SIM technology was developed by Mats G.L. Gustafsson, PhD, John W. Sedat, PhD and David A. Agard, PhD, of UCSF; Agard is currently a Howard Hughes Medical Institute (HHMI) investigator at UCSF and Gustafsson is a group leader at HHMI’s Janelia Farm Research Campus.

Mats Gustafsson spearheaded the initial work and introduced SIM in 2000 while at UCSF. SIM takes advantage of moiré patterns, which are produced by overlaying one pattern with another. The sample under the lens is observed while it is illuminated by a special grid pattern of light. Several different light patterns are applied, and the resulting moiré patterns are captured each time by a digital camera. Computer software algorithms then extract the information in the moiré images and translate it into two- and three-dimensional, high-resolution reconstructions.

Effective for live-cell imaging, N-SIM provides the fastest imaging capability in the industry, with a time resolution of 0.6 sec/frame. The newly developed TIRF-SIM illumination technique enables total internal reflection fluorescence (TIRF) observation with higher resolution than conventional TIRF microscopes and gives more detailed structural information near the cell membrane. In addition, another new 3D-SIM illumination technique has the capability of optical sectioning of specimens, enabling the visualisation of more detailed cell spatial structures.

“Nikon is greatly anticipating this exciting new development into the realm of super resolution and providing scientists with exceptional optical instrumentation that enables biologists and neuroscience researchers to visualise cellular structures and molecular activity at nearly twice the image resolution than realised before by conventional light microscopy in a commercialised microscopy system,” stated Stan Schwartz, vice president, Nikon Instruments, Inc. “We are excited with this opportunity to collaborate with UCSF and progressing together with Nikon’s design engineers to extend the capabilities and uses of N-SIM microscopy.”

Nikon’s official name for the commercialised system is Super Resolution Microscope N-SIM, and it will be available in May 2010. This news follows on from Nikon’s recent announcement about the revolutionary N-STORM Super Resolution microscope system, confirming its reputation as an innovator of advanced optical instruments.



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