The first commercial ultra-high resolution microscope using structured illumination developed at UC San Francisco (UCSF) by researchers funded by the Center for Biophotonics Science and Technology (CBST) and built by high-end research equipment maker Applied Precision is now in operation at the Oak Park Research Building at the Sacramento campus of UC Davis
SACRAMENTO, CA – June 9, 2008– Scientists at the Center for Biophotonics Science and Technology (CBST) and UC San Francisco (UCSF), working with engineers from Applied Precision (Issaquah, WA), have installed the first commercial version of the world’s highest resolution wide-field light microscope at CBSTs headquarters at the Sacramento campus of UC Davis. A prototype microscope, dubbed OMX for Optical Microscopy eXperimental, has been developed over the last five years by researchers working at UC San Francisco (UCSF) led by Professor John Sedat in a long-term collaboration with Professor David Agard.
“OMX is a breakthrough technology in microscopy because it overcomes a long-standing barrier, the diffraction limit of light, to significantly increase the resolution of light microscopes,” said CBST director Dennis Matthews. "The implications for medicine are profound. It's clear that the foundations of disease lie far deeper in cell structures than we can currently observe. With OMX, it is possible to see those cellular structures and how they 'talk' in real time. Our UC Davis researchers will now be able to better define disease processes and, ideally, find clues to reversing those processes as well."
For decades, many journals and textbooks have referred to the diffraction limit as an insurmountable barrier. However, an imaging technology called Structured Illumination (SI) -- recently invented by Mats Gustafsson working as post-doctoral researcher with Sedat and Agard and colleagues at UCSF -- has enabled scientists to overcome this limit. In SI, the object to be imaged is illuminated by a specific pattern of light that looks much like a bar code, rather than a uniform field of light like that from a lamp. This bar code-like pattern of light will produce unfocused – or moiré -- patterns that can be resolved by the microscope. Sophisticated software algorithms reconstruct a three-dimensional ultra-high resolution image from multiple individual images generated with the illumination pattern at different orientations and translations.
OMX is an important advance for researchers in all of the life sciences because microscopes are, “without a doubt the most valuable tool in biomedical research. They are unsurpassed in the return on investment they provide to researchers when it comes to obtaining dynamic visual information about living systems,” said Sedat.
The system installed at CBST has already demonstrated a two-fold improvement in resolution compared to the best conventional light microscope. Gustafsson, Eugene Ingerman, a UC Davis post-doctoral researcher, and Richard London, a researcher at Lawrence Livermore National Laboratory, showed that by employing non-linear effects, SI has the potential for a 10-fold improvement, which would allow for imaging cells down to a resolution of 25 nm. In addition to ultra-high resolution images, the OMX microscope is also capable of operating in a second mode that produces rapid multi-wavelength 3D images of live samples to study dynamic processes.
The patented SI technology, software algorithms, and system architecture were licensed by UCSF’s technology transfer office to Applied Precision who has worked closely with CBST to develop and install the first commercial OMX system. This system was purchased by CBST with the aid of a Major Research Instrumentation grant from the National Science Foundation.
“The OMX technology is a revolutionary leap in light microscopy and we are privileged to have been chosen to commercialize the OMX system,” said Applied Precision CEO Ron Seubert. “We look forward to working with the researchers at CBST and UCSF to complete our development and make this technology available to the life sciences community,” added Joe Victor, president at Applied Precision.
“We’re very excited to see this new CBST-developed technology be commercialized by Applied Precision. This project is one more example of CBST reaching its mission of using light-based technology to solve major problems in the life sciences and medicine,” said Matthews.
“This system opens the door to a new era of cellular imaging. With the first installation of the OMX system, CBST reinforces itself as a world-leader in optical microscopy research. CBST researchers, collaborators and sponsors now have access to this state-of-art instrument to make new discoveries in fields such as infectious disease, neuroscience, cancer, regenerative medicine and cardiovascular disease,” Matthews added.
Bruce Lyeth, a UC Davis professor of neurological surgery, and his post
doctoral fellow, Gene Gurkoff, are the first to utilize the OMX technology. A specialist in post-accident brain injury, Lyeth is most excited about the opportunity to view intricate changes in brain cells after traumatic events.
"The OMX helps us visualize living cells and their interactions at several times the resolution value of what current technology offers," Lyeth said. "This gives us the unique chance to replicate brain injury in the lab, then actually watch the changes in brain cell structure at the tiniest level. We can see neurons and how neuronal components communicate post-injury. We can then identify the specific cells that are best able to withstand trauma and identify therapeutics to reduce damage and encourage healing for those that don't."
The breast cancer research team at UC Davis is looking forward to
utilizing the OMX to evaluate cell changes that promote malignancy.
"We know that alterations in the properties of cell surface proteins play a dramatic role in regulating the growth of tumors, but we have so far been unable to fully understand this process since the protein clusters involved are significantly smaller than what we are able to see clearly with current microscopy," said Kermit Carraway, co-director of the breast cancer research program at UC Davis Cancer Center. "The power of the OMX system will allow us a more clear view of the proteins involved along with insights into the mechanisms by which they subvert healthy cell growth and promote malignancy. This will definitely lead us to treatments that help reduce opportunities for tumor metastasis."
For more information about the OMX, please visit here
The National Science Foundation commissioned the Center for Biophotonics, Science and Technology (CBST) in 2002, with a mission to harness the power of light to solve major challenges in the life sciences and medicine through innovative research, commercialization and comprehensive educational programs. From its headquarters at the UC Davis Medical Center, CBST coordinates activities with its core group of eight university campuses and one national laboratory, and is building an extensive worldwide network of schools, industrial partners, and other research centers. The Center has three main programs: Research, Education, and Knowledge Transfer. For more information, visit www.cbst.ucdavis.edu
About Applied Precision, Inc.
Applied Precision is a leading provider of imaging, measurement and analysis systems for the life sciences Industries and OEM markets. Headquartered just outside of Seattle, Washington with sales centers in both Europe and Asia, Applied Precision has received multiple awards for its innovative new products. The company has also received recognition for its financial growth and is a five-time winner of the Deloitte & Touché Washington State Technology Fast 50 award. More information about Applied Precision is available at www.appliedprecision.com