Wireless optogenetic control of the brain
Optogenetics, a recently developed technique that uses light to map and control brain activity, requires the genetic modification of an animal’s brain cells and the insertion of optical fibers and electrical wire into its brain. The bulky wires and fibers emerge from the skull, hampering the animal’s movement and making it difficult to perform certain experiments that could lead to breakthroughs for Parkinson’s disease, addiction, depression, and spinal cord injuries.
But now, a new ultrathin, flexible device laden with light-emitting diodes and sensors, both the size of individual brain cells, promises to make optogenetics completely wireless. The 20-micrometer-thick device can be safely injected deep into the brain and controlled and powered using radio-frequency signals. Its developers say the technology could also be used in other parts of the body, with broad implications for medical diagnosis and therapy.
In optogenetics, scientists genetically modify neurons to make them sensitive to particular wavelengths of light. Shining light on the altered neurons turns them on or off, allowing scientists to control specific brain circuits and change animal behavior.
The implant is a stack of four different optoelectronics devices that the researchers create separately on flexible polymer substrates and then glue on top of one another. The topmost layer is a platinum microelectrode for stimulating and recording from neurons. Below that is a silicon photodetector, followed by a group of four microscale LEDs that are each just 50 by 50 micrometers. Last comes a platinum-based temperature sensor. The filament carrying the stack is glued onto a microneedle with a silk-based glue that dissolves once the device has been injected into the targeted spot, allowing the researchers to retract the microneedle.
The technique for making the membranous devices is not new. Developed a few years ago in Rogers’s lab, it involves growing stacks of thin semiconductor films, peeling them off one at a time with a rubber stamp, and transferring them to plastic substrates.
Scientists could use the multifunctional system to stimulate and sense the brain in a variety of ways, Bruchas explains. The microelectrode can measure the electrical signals produced by neurons, and it can also be used to stimulate them. The photodiodes ensure that the LEDs are working, but they can also be used to detect light signals generated by neurons that have been genetically modified to make certain fluorescent proteins.
The micro-LEDs, which have dimensions comparable to individual neurons, could trigger individual neurons, unlike the fiber-optic implants typically used in optogenetics, which are four times as wide. The researchers could also combine different-colored LEDs on the same device and use them to simultaneously control neurons that have been engineered to react to different colors. Such multiplexing would allow neuroscientists to analyze brain circuits more precisely, Bruchas says. Finally, the temperature sensor monitors the heat generated by the LEDs to prevent the tissue from overheating.
When the researchers placed the device—which connects to an RF power module mounted on the animal’s head—inside the brains of living mice, it caused no inflammation or infection. To test the system’s ability to alter animal behavior, the researchers embedded it near a particular group of neurons that they had genetically altered to release dopamine when cued with light. The neurochemical dopamine is involved in the body’s “rewards” system, such as with food or sex, and it plays a part in several addictive drugs.
ABSTRACT – Successful integration of advanced semiconductor devices with biological systems will accelerate basic scientific discoveries and their translation into clinical technologies. In neuroscience generally, and in optogenetics in particular, the ability to insert light sources, detectors, sensors, and other components into precise locations of the deep brain yields versatile and important capabilities. Here, we introduce an injectable class of cellular-scale optoelectronics that offers such features, with examples of unmatched operational modes in optogenetics, including completely wireless and programmed complex behavioral control over freely moving animals. The ability of these ultrathin, mechanically compliant, biocompatible devices to afford minimally invasive operation in the soft tissues of the mammalian brain foreshadow applications in other organ systems, with potential for broad utility in biomedical science and engineering.