June 19, 2008 -- Scientists at the UC Davis Center for Biophotonics Science and Technology (CBST) in Sacramento, CA have installed the first commercial version of the world's highest resolution wide-field light microscope. The microscope, called OMX (short for Optical Microscopy eXperimental), allows cellular processes to be viewed at the smallest possible levels and as they occur, providing significant advantages to researchers seeking to understand and treat disease.
"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. With OMX, it is possible to see sub-cellular structures and how they respond to stimuli 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."
The OMX was developed over the last five years at UCSF by professors John Sedat and David Agard. UC Davis was chosen as the first site for the technology because of CBST's financial support for the project, along with the center's leadership in using light-based technology to solve major obstacles in the life sciences and medicine.
For decades, the diffraction limit has been an insurmountable barrier to medical researchers wanting to view cellular processes as they occur. Other options -- like the electron microscope -- are high resolution but cannot be used to view living samples. Optical fluorescence microscopy allows imaging of live samples, but is relatively low-resolution. The OMX utilizes a new imaging technology called structured illumination (SI), invented by UCSF postdoctoral researcher Mats Gustafsson, that overcomes these limitations. With SI, a carefully designed pattern of light is used to illuminate an object. The pattern of light looks like a bar code rather than a uniform light field such as what a standard lamp provides. This bar code produces unfocused -- or moiré -- patterns that are then resolved by the microscope. Sophisticated software is used to digitally reconstruct three-dimensional, ultra-high-resolution images on a computer screen from the multiple individual images generated with the illumination pattern. In addition to ultra-high-resolution images, the OMX has a second mode of operation that produces rapid multi-wavelength, three-dimensional images of live samples for the real-time study of cellular processes in action.
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. SI has the potential for a 10-fold improvement, which allows for imaging cells and cell components as small as 25 nanometers, such as an axon - the long and extremely thin extension of a neuron that carries information to target cells -- and vesicles within cells that store, transport or digest cellular materials like lipids.
"This technology opens the door to a new era of cellular imaging and reinforces CBST as a world leader in optical microscopy research," said Matthews. "Our 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."
Bruce Lyeth, UC Davis professor of neurological surgery, and post-doctoral fellow Gene Gurkoff are the first to utilize the OMX technology at UC Davis. 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 a quality of detail far exceeding previous capabilities. 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 closely evaluate cell changes that support the growth of malignancies.
"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 clearer view of the proteins involved along with insights into the mechanisms by which they subvert healthy cell growth and promote cancerous lesions. This will definitely lead us to treatments that will thwart tumor progression and metastasis."