Tissue integrated neural electrodes

Implanted neural probes are among the most important techniques in both fundamental and clinical neuroscience. Scientifically, they remain our only practical option to resolve the fast electrophysiological activities of individual neurons, which provides critical information to dissect the neural circuitry. Clinically, neural electrodes have been successfully used in a number of treatments for neurological disorders, such as deep brain stimulation and peripheral nerve stimulation. Further, they allow for direct communication between the brain and man-made devices, which could enable futuristic applications such as human brain-machine interface and neuroprosthetics. Despite great successes and promise, neural electrodes are significantly limited by their unstable performance and substantial invasiveness. Not only its recording can change in timescale as short as minutes, it also induces damages to the brain tissues both acutely and chronically. A reliable neural interface has been pursued for decades but remains highly challenging. Fundamentally, this instability arises from the distinct physical mismatch at the neural electrode-tissue interface. First, the relatively large size of neural probes compared with tissue components, such as cells and capillaries, induces unavoidable tissue displacement and damage during implantation, and their persistent presence interrupts local biological functions and triggers immune responses. Second, their mechanical stiffness causes poor integration in tissues, and more importantly, strong interfacial forces that elicit sustained tissue responses, neuronal loss, scar tissue accumulation, and interface performance deterioration. Recently, our laboratory has created an ultraflexible nanoelectronic neural probe and demonstrated the possibilities of suppressing scarring and achieving reliable long-term neural recording. Furthermore, we used in vivo two-photon imaging to reveal the seamless, subcellular integration of these probes with the local cellular and vasculature networks, including fully recovered capillaries with intact blood-brain barrier, and complete absence of chronic neuronal degradation and glial scar. Building upon this technical breakthrough, we are now capable of tuning into individual neurons in neuronal circuitry and track their activities for many months.