Integrating neuroscience with materials engineering could establish a paradigm for delivering sophisticated electronics into the body. Materials scientists and engineers at the University of Illinois at Urbana-Champaign and neurobiologists at Washington University in St. Louis injected microLEDs deep into the brains of mice to study their structure, function and complex connections. The specially designed LEDs – developed in the lab of John A. Rogers at the University of Illinois – are printed onto the tip of a thin, flexible plastic ribbon that can be deeply inserted with very little stress to tissue. The microLED device implanted in a rodent’s brain to demonstrate the optical properties of devices in intact tissue. Courtesy of University of Illinois at Urbana-Champaign and Washington University in St. Louis. “One of the big issues with implanting something into the brain is the potential damage it can cause,” Michael R. Bruchas, a professor of anesthesiology at Washington University told BioPhotonics. “The device delivery and ultrathin design of the final device (after removal of the silk-adhesive injector system) is 25 µm thick in the mouse brain. We showed in the study that typical markers of tissue damage, lesioning and inflammation were dramatically decreased using this ultrathin method.” Previous techniques to study neural pathways tethered the animals to lasers with fiber optic cables embedded in the skull and brain – an invasive procedure that limits movement, affects natural behaviors and prevents study of social interactions. In studies conducted using a Y-shaped maze paradigm, Bruchas and colleagues assessed the conditioned behavioral responses and operant reward behavior in the mice. At the end of each of the maze’s arms are nose-poke devices connected to transistor-transistor logic output and the radio frequency modulator. A thin plastic ribbon printed with advanced electronics is threaded through the eye of an ordinary sewing needle. The device, containing LEDs, electrodes and sensors, was developed by researchers at the University of Illinois at Urbana-Champaign and at Washington University in St. Louis. It can be injected into the brain or other organs. Courtesy of John A. Rogers, University of Illinois at Urbana-Champaign. “Since we selectively expressed a light-sensitive channel in the mouse dopamine neurons, whenever they poke the ‘active’ arm, they receive a light pulse into their dopamine neurons via the wireless LED device,” Bruchas said. “Over the course of days, the mice learn to increase this nose-poke behavior because they in effect are self-stimulating their dopamine reward pathways. They become sort of ‘hooked’ on the light-pulse stimulation.” “The systems we have developed allow the animals to move freely and to interact with one another in a natural way, but at the same time, provide full, precise control over the delivery of light into the depth of the brain,” Rogers, the Swanlund professor of materials science and engineering, said in a university release. The researchers also can control the depth to which the device is injected. “There is no limit to how far we can inject this device,” Bruchas said. “We simply make different lengths or sizes to meet the tissue depths and needs of the experiment we are conducting or the brain region of interest.” Although the microLEDs are not yet ready for use in humans, it is an exciting prospect, Bruchas said. “The gene therapy technology to express light-sensitive proteins in selected neurons is not yet available in humans, so we’d currently be unable to implement this feature,” he said. “However, gene therapy is moving rapidly, and there is potential in that regard going forward. Furthermore, the novel technology’s biocompatible nature will surely have some application to human device development.” Next, the researchers hope to use the device “to dissect selected neural circuits involved in stress behaviors, social interaction and pain states,” Bruchas said. “Working together with the research team at the University of Illinois and brainstorming solutions to problems was a lot of fun for both groups,” Bruchas said. “Combining these two disciplines in unique ways to address biological and health-related problems will continue as our two groups go forward.” The work appeared in Science (doi: 10.1126/science.1232437).