The first completely implantable optogenetics stimulator has a price point so low that research labs with tight budgets can afford to investigate the technology.
|The optogenetic stimulators recently developed at Stanford are the first that are completely implantable. Image: Brian Buntz.|
One of the hottest research topics in neuroscience, optogenetics has given scientists unprecedented control of the brain. In mice studies, researchers have used the technology to beam light at targeted neurons to activate or deactivate them, potentially altering how the mice behave or feel in near real time. Researchers have used optogenetics to help numb mice in pain and to even reshape their memories of fearful events. Optogenetics has also led to breakthroughs in understanding diseases in humans, adding to our understanding of diseases ranging from depression to Parkinson's.
Now, Ada Poon, PhD, a Stanford professor of electrical engineering, has announced that her research team has developed the first miniature, completely implantable, optogenetic device. "When turned off, you don't see any implant unlike the current solution. When switched on, light can be seen leaking out of the mouse's skull."
The wireless stimulator costs a mere $10 to make and enables mice be tracked within a 16-cm radiofrequency cavity. Poon's entire optogenetic system costs roughly $5000 to build.
"People ask us if they can mass produce them and we say: 'just hire some undergraduates and have them follow this video here," Poon says. "We want any school with a limited budget to be able to do optogenetic research."
(Ed note: Poon will be speaking at MD&M Philadelphia on powering implantable devices without batteries on October 7.)
The new device is completely implantable, allowing the mice to roam freely. "It does not affect the behavior of the mouse," Poon says. Up until recently, mice studies have tethered mice to a fiber optic strand plugged into a brain implant or used bulky head-mounted devices. In the first case, the fiber optic cable attached to a mouse's head can get tangled and can disrupt its ability to navigate. The earlier wireless device was a head-mounted unit weighing roughly as much as the mouse's head.
The researchers wanted to make a simple technology that could support a relatively large coverage area for the miniature device.
Inspired by quantum tunnelling, they came up with an elegant solution power the technology: power the device wirelessly, using the mouse itself as a dielectric resonator.
|An implantable optogenetic implant stimulates leg nerves in a mouse. Image: Ada Poon.|
"Because it has a high concentration of water, a mouse is a good dielectric resonator," Poon says.
The researchers built a radiofrequency cavity with holes in the top. "When there is no animal inside it, all of the energy retracts. But when there is an animal inside, because it very dense, the energy will be automatically extracted," Poon. "This enables self tracking. I don't need any more electronics to track where the animal is, which would require localized power." When a mouse is within it, it leaks energy through the holes at the top, which is then absorbed by the coils implanted into the mouse brain.
The approach is much simpler compared with others that have come before it. For instance, one approach investigated the use of a network of coil's beneath the mouse's cage. Determining where the mouse was in the cage, a coil would turn on or off. "That system is like a cellphone tower for humans. I couldn't convince myself to make something so complicated for a mouse," Poon says.
But treating the mouse as a dielectric resonator was not without its own challenges. "It seemed like the most ridiculous thing we have done in our academic career--studying the resonant electromagnetic modes of a mouse in different orientations," Poon jokes.
|An earlier groundbreaking implantable wireless optogenetic stimulator protruded from a mouse's head in contrast to the fully implantable Stanford device. The technology shown above was developed by researchers at Washington University School of Medicine in St. Louis and the University of Illinois at Urbana-Champaign and was published in Science.|
Research associate Yuji Tanabe even created diagrams demonstrating the mouse as a dielectric resonator.
In one study, the researchers implanted the stimulator in the right motor cortex. When the unit was switched on, the mouse moved counterclockwise in a circular cage. Poon jokes that adding a second stimulator to the left motor cortex would enable them to make the mouse remote-controllable.
However, the small size of the device does open up numerous potential applications, enabling custom versions of the stimulators to be implanted at various points throughout the body, Poon says. "We can stimulate the spinal cord or peripheral nerves," she says.
Already, the Stanford team has used the technology in a pain study. "Current, researchers use a reflexive measure for pain studies for drug testing. In this approach, a pain stimulus is administered to mice and the reaction time is measured," Poon says. Measuring sedated and non-sedated mice this way provides a determination for the efficacy of an analgesic drug. "But a lot of drugs that pass in an animal model don't work in humans. Genetically modifying mice to feel pain when light is optogenetically administered to the brain provides a new mechanism for studying painkillers. The researchers recently received a grant to investigate this research, which could provide a new data-driven method of studying pain.
Inspired by the Open Source movement, Poon has not only released instructions for the system, but her team has produced a YouTube video (embedded above) demonstrating how to show potential optogenetic researchers how to build their own systems. A separate video (see below) covers the soldering of the device. The researchers have also shared a parts list for the project, including information on where to purchase specific components--all of which are available off-the-shelf. "Our goal is that a non-engineer should be able to make it," says Stanford research associate Yuji Tanabe.
|Learn more about medical applications of cutting-edge implants at MD&M Philadelphia, October 7-8, 2015.|