Looking to the future

By David F. Salisbury
Oct. 9, 2001

Biophotonics—the application of light to illuminate and manipulate the hidden worlds of living organisms—is the future direction that Vanderbilt's free-electron laser center is taking.

"We envision ourselves as taking a leading role in exploring and applying new knowledge about the interactions of photons and biomaterials," says center director David Piston.

Building on existing programs, including the FEL surgery, development of the monochromatic X-ray and use of the FEL for protein identification, this represents an ambitious expansion of the range of the center's activities.

Until recently the center has been a one-horse operation, almost entirely centered on the free-electron laser. But the successful development of the monochromatic X-ray machine will soon add a second novel light source to its research repertoire. In the future, Piston would like to add at least two more new light sources.

The FEL was originally designed and constructed with funding from the Department of Defense as part of the Strategic Defense Initiative and the DOD has continued to provide the lion's share of funding. In fiscal year 2001/2002, for example, it is providing $2.5 million out of the total $3 million in the center's external funding. The National Cancer Institute is contributing $400,000 and the remainder comes from three additional research grants from the National Institutes of Health.

"Our support from the Department of Defense is solid, and will continue to play a major role in the center's operation," says Piston, "but we have set a high priority on diversifying our funding base."

The center is concentrating on four major research areas:

• Materials science. Center researchers have considerable expertise in thin films, organic materials, nanocrystals, magnetic materials and glasses. One of their current projects is the development of a new kind of microscope that uses the infrared light from the free-electron laser. Developed in collaboration with researchers from the University of Rome and the Naval Research Laboratory in Washington, DC, the scanning near-field optical microscope (NSOM) can achieve a spatial resolution of a few hundred nanometers with wavelengths in the one to seven micron range. This capability could have a major impact on materials and biophotonics research. The scientists have begun applying this technique to applications ranging from mapping the electronic structure of semiconductors near surfaces and interfaces to the examination of chemical components in biological cells.
• Laser surgery. For ten years, center scientists have built up an extensive base of knowledge of the way that the unique FEL beam interacts with human tissue and have identified the specific wavelengths that can cut soft tissue and bone with a minimum amount of damage to adjacent areas. In the last two years, this knowledge has been applied to a series of surgeries with human patients that have been completely successful. In fact, the biggest surprise has been that the operations went exactly as expected. So far, operations have been done exclusively by Vanderbilt surgeons. In the future, medical researchers from Duke and Stanford will also be participating. The center is also supporting research to develop smaller and less expensive solid-state lasers that can duplicate the characteristics that make the FEL beam such an effective light scalpel.
• Proteomics. Determining the function of the myriad of proteins that play essential roles in living systems is vital to applying the knowledge gained from the mapping of the human genome to finding new ways to treat and prevent disease. Using the FEL beam to simplify and speed up the method currently being used to identify proteins appears likely to play an important role in this rapidly emerging field. This technique, called IR-MALDI, has the potential for identifying proteins in very small samples, and might even allow the analysis of the proteins in single cells.
  
  In addition, the monochromatic X-ray has the capability for drastically reducing the time and the difficulty involved in determining protein structures through X-ray crystallography. This is the premier method for determining the structures of complex biomolecules, but can only be done at a handful of synchrotron laboratories associated with major particle accelerators. The center plans to construct a second monochromatic X-ray device for this purpose.
• In Vivo Imaging. Imagine being able to watch the movement of a single molecule inside the body of a living animal! The center is using a number of novel techniques, to achieve this goal. One approach is to use mice that have been genetically engineered to produce special proteins that fluoresce when illuminated with laser light and then to insert optical fibers into the mouse's body to excite these molecules and trace their motion.
  
  Another is to use the monochromatic X-ray to produce three-dimensional images of internal organs with an unprecedented level of detail. Such a capability should shed important new information about diseases such as cancer and diabetes.

In the 1960's, lasers were characterized as a technology in search of an application. Today, they are everywhere. Their remarkable success demonstrates just how important new light sources can be, both as a research tools and as components in new technologies. Both the FEL and the monochromatic X-ray have unique characteristics that virtually guarantee that they will be the source of valuable new information about living systems and will provide the basis for important new technologies in years to come.

VUMC Reporter article on In Vivo Imaging Center
http://www.mc.vanderbilt.edu/reporter/index.html?ID=1188