To accomplish his goal, Foulger is creating a completely new kind of bioimaging material.
“We’re trying to replace some of the fiber optic cabling that goes into the brain for optogenetics,” Foulger explains. “Instead of using fibers that go into the brain, we want to use radioluminescent particles and X-ray sources to generate light in these localized positions.”
The idea, he says, is to create tiny particles coated with light-producing materials that could then be injected via a shot and directed to infiltrate a targeted spot in the brain. When hit with a focused X-ray, the coating would emit light at a characteristic wavelength and activate nearby light-sensitive proteins, which change shape to drive neuronal firing.
Foulger and two collaborators, neuroscientists Lori McMahon at the University of Alabama at Birmingham and Jason Weick at the University of New Mexico, won a $6 million grant from the National Science Foundation to tackle this challenge. It’s a highly collaborative project designed to cross disciplines. Weick, a molecular biologist, is developing a method to get the light-sensitive proteins, called opsins, into brain cells. McMahon, a neurophysiologist, is exploring how to use X-ray-triggered particles to control brain circuits. And Foulger, as the materials scientist and director of Clemson’s Center for Optical Materials Science and Engineering, is responsible for creating the requisite particles. The NSF project naturally falls within COMSET’s scope of research on materials that generate, convey or manipulate light.
Ideally, the particles should be no more than 100 nanometers in diameter — roughly one-seventieth the width of a human hair — to pass through blood vessels and collect in the brain without causing damage. They need to work effectively in living tissue. And they must produce enough light to trigger the opsins, with as little X-ray exposure as possible.
“It’s a challenge,” Foulger says. “Making a sub-100-nanometer radioluminescent particle hasn’t been done. So, it’s a basic materials science problem.”
In the first years of the project, his group has successfully developed submicrometer ceramic particles doped with the rare earth element cerium and coated with light-emitting molecules called fluorophores. They are now testing materials with different emission wavelengths and characteristics — how much light the molecules produce and how well they pair with the sometimes-finicky absorption characteristics of the light-sensitive proteins called opsins. It can be a bit of a moving target, as opsin development is itself a complex, developing field.
“There are many kinds of these proteins, and they have different responses to light,” says McMahon. “We have to do a lot of testing to find out which light-sensitive protein and which of the particles that Dr. Foulger’s lab has made are the best ones to pair together.”