Full bandwidth electrophysiology of seizures and epileptiform activity enabled by flexible graphene micro-transistor depth neural probes

ABSTRACTMapping the entire frequency bandwidth of neuronal oscillations in the brain is of paramount importance for understanding physiological and pathological states. The ability to record simultaneously infraslow activity (<0.1 Hz) and higher frequencies (0.1-600 Hz) using the same recording electrode would particularly benefit epilepsy research. However, commonly used metal microelectrode technology is not well suited for recording infraslow activity. Here we use flexible graphene depth neural probes (gDNP), consisting of a linear array of graphene microtransistors, to concurrently record infraslow and high frequency neuronal activity in awake rodents. We show that gDNPs can reliably record and map with high spatial resolution seizures, post-ictal spreading depolarisation, and high frequency epileptic activity through cortical laminae to the CA1 layer of the hippocampus in a mouse model of chemically-induced seizures. We demonstrate functionality of chronically implanted devices over 10 weeks by recording with high fidelity spontaneous spike-wave discharges and associated infraslow activity in a rat model of absence epilepsy. Altogether, our work highlights the suitability of this technology for in vivo electrophysiology research, in particular, to examine the contributions of infraslow activity to seizure initiation and termination.

Fabrication of a novel liquid metal microelectrode in microfluidic chip

Electrokinetics is a good fluid control tool in microfluidics and usually microelectrodes play important roles in such approach such as generating a desired electric field. Though the fabrication of two-dimensional (2D) microelectrodes has been relatively mature, they cannot generate uniform electric field in space. Three-dimensional (3D) microelectrodes developed more recently may solve the problem, however the fabrication process is usually complicated and requires micro-alignment platform. Non-toxic liquid metal is a good material for making electrodes that has been introduced into microfluidics. It can be injected directly into a microchannel to form an electrode, but its special physical properties make the injection process complex and difficult to control. In this study, we investigated an optimized manufacturing method of liquid metal microelectrode in a microchip by numerical analysis and experimental study. High quality microelectrodes on morphology and stability were successfully fabricated. A fluorescent enrichment experiment was performed using the developed microelectrode in a microfluidic chip. The result shows that the optimized fabrication method of microelectrode in this study provides a promising way for high quality and good performance liquid metal microelectrode formation, and paves the way for its versatile applications.