Transparent neural interfaces for simultaneous electrophysiology and advanced brain imaging

Abstract

Imaging and electrophysiology are the most fundamental tools in neuroscience research. On the one hand, optical imaging can target specific molecules with high spatial resolution in vitro and in vivo. Spectroscopic techniques like magnetic resonance imaging (MRI) can access deep regions of the brain over a large area and is the state-of-the-art in clinical brain imaging. On the other hand, microelectrode arrays (MEAs) and neural probes are indispensable in deciphering the electrical activity of neurons. Unfortunately, simultaneous imaging and electrophysiology is challenging with conventional metal electrodes which are non-transparent. In MRI, the issue is compounded by the heating effect in metals and loss of signal due to their significantly different magnetic susceptibility compared to biological tissue. Conducting polymer electrodes are prospective alternatives since their compositions are closer to biological tissues. Poly(3,4-ethylenedioxythiophene) doped with polystyrene sulfonate (PEDOT:PSS), one of the most widely used conducting polymers, exhibits volumetric capacitance effect which reduces electrode impedance and significantly improves the signal-to-noise ratio of neural interfaces. This work presents PEDOT:PSS-based optically transparent and MRI compatible MEAs. To begin with, a scalable and repeatable patterning technique of PEDOT:PSS on glass was developed which manifested in in vitro MEAs. The PEDOT:PSS electrodes exhibited superior electrochemical properties than other alternative transparent conductors. The transparent MEAs enabled simultaneous electrical recordings and Ca2+ imaging from neurons and allowed super-resolved imaging of diffraction limited cellular structures in addition to state-of-the art fluorescence imaging. Subsequently, the MEAs were implemented for studying the spread of tau pathology in neurodegenerative diseases and its effects on overall neuronal activity. They were integrated into a microfluidic neuronal culture platform to selectively examine the activity-dependent uptake of tau protein at the pre-synapse. Next, the in vitro glass-based transparent MEAs were translated into ultra-thin flexible MEAs for in vivo applications. As micro-electrocorticography (µECoG) arrays, the flexible MEAs enabled MRI imaging with minimal artifacts and showed promise for simultaneous functional MRI and electrophysiology. The structure of the flexible MEAs were also favourable for long-term organoid cultures and a modified design enabled continuous electrophysiology for weeks. It is expected that the versatile, transparent PEDOT:PSS MEAs would add new capabilities to neuroscience research by enabling complementary electrophysiology and multi-modal imaging.