MIT graduate student Chi (Alice) Lu designs a flexible polymer probe to trigger neurons with light and record that activity in the spinal cord of laboratory mice.
|MIT graduate student Chi (Alice) Lu in the laser lab where she tests her flexible polymer probe. Photo: Denis Paiste, Materials Processing Center|
Optical stimulation of neurons in the spine is much harder than in the brain, says MIT Program in Polymer Science and Technology graduate student Chi (Alice) Lu, who is carrying out laboratory experiments with genetically altered mice.
Although optogenetics, a method that makes mammalian nerve cells sensitive to light via genetic modification, has been applied extensively in investigation of brain function over the past decade, spinal cord research has lagged, says Lu, who developed a flexible neural probe made entirely of polymers that can simultaneously optically stimulate and record neural activity. “Working in a spinal cord is significantly more difficult than in the brain because it experiences more movements. The radius of the mouse spinal cord is about 1 millimeter, and it’s very soft, so it took me some time to figure out how to do the surgery and perform the stimulation and recording without damaging that tissue,” she explains.
Lu is lead author of “Polymer Fiber Probes Enable Optical Control of Spinal Cord and Muscle Function In Vivo,” with senior author Polina Anikeeva, AMAX Assistant Professor in Materials Science and Engineering, and colleagues at the Research Laboratory of Electronics, Simons Center for the Social Brain and McGovern Institute for Brain Research. Prof. Yoel Fink provided access to the fiber-drawing tower. The article has been accepted for publication in Advanced Functional Materials.
The researchers conducted experiments with their neural probe in mice, that express the light-sensitive protein channelrhodopsin 2 (ChR2) that makes their neurons respond to blue light. These mice, developed by Prof. Guoping Feng and colleagues at the McGovern Institute for Brain Research provide a convenient model system for optoelectronic neural prosthetics. “When we shine light in, we can directly observe neuronal response by getting an electrical recording,” explains Lu, 24, who will be entering the third year of her doctoral program in the fall. She designed the polymer fiber with a waveguide for optical stimulation and conductive polyethylene (CPE) electrodes for recording of neuronal electrical activity. The device may have potential future applications for spinal or peripheral nerve prosthetic devices.
“Laser pulses … delivered through the PC (polycarbonate) core of the fiber probe robustly evoked neural activity in the spinal cord, as recorded with the CPE electrodes integrated within the same device,” the researchers report.
Lu says the fiber was drawn from a template nearly 1.5 inches thick to the final thickness, which is comparable to human hair. It is so flexible it can be tied in a knot, Anikeeva points out. Repeated deformation tests showed the fiber held up well under stress expected from normal body movements.
Although Lu’s optical probe works with transgenic mice, the technology will need further development before it can be considered for therapeutic applications, because human neurons, with the exception of those in the eye, are not sensitive to visible light. However, Lu says, similar results can be achieved in genetically intact animals by delivering ChR2 gene using a virus, a technique called viral transfection. Over time, the viral gene delivery causes the neurons to produce ChR2 and become sensitive to blue light.
Still, the researchers report their polymer probes as a step towards developing flexible biomimetic optoelectronic neuroprosthetics. Anikeeva would like to extend the fiber work to interfacing with nerves for prosthetic devices, for example, integrating a prosthetic limb with what’s left after an amputation.
Lu says the next step will be a chronic study. “I think the challenge will be how to implant even a very flexible device without paralyzing the animal. We are just interfacing something harder than the tissue with the body. And then when the animal moves, the device has to follow this movement organically otherwise it will potentially paralyze the animal. So this will be another challenge, how to find a good spot for stimulation and recording but not damage the tissue,” she says.
– Written by Denis Paiste, Materials Processing Center