UC San Diego

The advancement of neuroscience research often requires recording of complex neural activities at high spatiotemporal resolution. Electrophysiology, being the backbone of neuroscience for decades, has the advantage of high temporal resolution, yet lacks the high spatial resolution of fluorescent imaging at single cell level. On the other hand, fluorescent imaging suffers from low temporal resolution due to the slow kinetics of the indicators. Recently, optogenetics revolutionized the capacity to control selective neural populations and provides researchers with unprecedented opportunities to investigate the causal relationships among different brain circuits. However, the traditional neural electrode arrays based on silicon and noble metals are opaque and hence not suitable to integrate electrophysiology and optical modalities. This dissertation presents a novel transparent microelectrode array based on graphene that demonstrates crosstalk-free integration of electrophysiology, calcium imaging, and optogenetics in in vivo experiments on mice models.Chapter 1 reviews the recent progress in the field of graphene-based neurotechnology. Graphene is widely used for microelectrode, field effect transistor, chemical sensing, and cell culture owing to its flexibility, transparency, high conductivity, low noise, and biocompatibility. Chapter 2 presents a novel transparent graphene microelectrode array designed for multimodal neural interfaces. The fabrication process was designed to avoid crack formation and organic residue, which is essential to eliminate light-induced artifacts. In vivo experiments were conducted to demonstrate a crosstalk-free integration of electrophysiology, optical imaging, and optogenetics for the first time. Chapter 3 demonstrates that electrochemical impedance of graphene is fundamentally limited by the quantum capacitance. And to overcome such limit, we created an alternative conduction path with electrochemically deposited platinum nanoparticles and reduced the impedance by 100-fold while maintaining high transparency. Chapter 4 presents a flexible implantable transparent microelectrode array that enables simultaneous electrical recordings from hippocampus during optical imaging of neural activity across large areas. Our neural probe has three advantages, flexibility, transparency, and shuttle-free implantation. We demonstrated seamless integration of simultaneous wide-field fluorescence imaging of the cortex with electrical recordings from the hippocampus. Chapter 5 is the conclusion of this dissertation. The outlook and roadmap of graphene-based neurotechnology for both neuroscience research and medical applications are discussed.