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Patents Issued for Licensed PAL-M Super-resolution Technology

PAL-M image (right) and TIRF image (left) of antibody staining for tubulin in a cultured cell. Specimen: S. Niwa, University of Tokyo, Japan.The United States Patent and Trademark Office has issued three patents (US 7,626,694, US 7,828,695 and US 7,626,703) to Dr. Eric Betzig and Dr. Harald Hess for their invention relating to super-resolution Photo-Activated-Localization Microscopy (PAL-M). PAL-Microscopy is now protected by these patents. Carl Zeiss MicroImaging GmbH had acquired an exclusive license for the distribution of PAL-M in 2007.

The microscopy technology enables imaging of samples with a spatial resolution of a few nanometers.

The basic idea of the invention is to generate sparse subsets of fluorescent dye molecules at a time. This allows to accurately determine the position of those individual fluorescent molecules with nanometer precision. Thus, serial acquisition of images with consecutively phototransformed fluorescent molecules permits the generation of a super-resolved image by rendering the superposition of the localized molecules.

Carl Zeiss MicroImaging GmbH initiated the market launch of the ELYRA product family towards the end of 2009. This includes the first commercially available PAL-Microscope system ELYRA P.1 with a lateral resolution of less than 20 nm. This is a factor of 10 higher than in conventional light microscopes and, together with the very broad field of applications of the PAL-M technology, opens up new application potential for commercially available light microscopes.

In the ELYRA PS.1 microscope system, PAL- Microscopy is combined with Structured Illumination Microscopy (SIM), another super- resolution generating technology. The SIM technology was licensed by Carl Zeiss MicroImaging GmbH from the University of California in San Francisco in October 2009. The ELYRA product family microscopes can also be combined with the Laser Scanning Microscopes LSM 710 or LSM 780 from Carl Zeiss.

In their Nature Methods publication of December 2008 (vol. 6, no. 1), renowned researchers Jennifer Lippincott-Schwarz and Suliana Manley envisioned that super-resolution microscopy technologies have the potential to revolutionize the understanding of the fundamentals of cell biology. Meanwhile several research groups have demonstrated this potential in numerous high- quality publications.

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