Nature Nanotechnology, 2021, in press

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

Andrea Bonaccini Calia, Eduard Masvidal-Codina, Trevor Smith, Nathan Schäfer, Daman Rathore, Elisa Rodríguez-Lucas, Xavi Illa, Jose De la Cruz, Elena Del Corro, Elisabet Prats-Alfonso, Damià Viana, Jessica Bousquet, Clement Hébert, Javier Martínez-Aguilar, Justin R. Sperling, Matthew Drummond, Arnab Halder, Abbie Dodd, Katharine Barr, Sinead Savage, Jordina Fornell, Jordi Sort, Christoph Guger, Rosa Villa, Kostas Kostarelos, Rob Wykes*, Anton Guimerà-Brunet*, and Jose Garrido*

Mapping 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 DC potential recordings (<0.05 Hz) and and higher frequencies ( AC recordings  0.1-600 Hz) using the same recording electrode would particularly benefit preclinical epilepsy research and could provide clinical biomarkers for improved seizure onset zone delineation. Commonly used metal microelectrode technology suffers from instability that hampers the high-fidelity recording of infraslow activity. Here, we use flexible graphene depth neural probes (gDNP), consisting of a linear array of graphene microtransistors, to concurrently record DC potential recordings and high frequency neuronal activity in awake rodents. We show that gDNPs can reliably record and map with high spatial resolution seizures, concurrentDC baseline shifts and spreading depolarization with high frequency epileptic activity through cortical laminae to the CA1 layer of the hippocampus in a mouse model of chemically-induced seizures. Moreover, we demonstrate functionality of chronically implanted devices over 10 weeks by recording with high fidelity spontaneous spike-wave discharges and associated  DC potential changes in a rat model of absence epilepsy. Altogether, our work highlights the suitability of this technology for in vivo electrophysiology research, and in particular, in allowing stable and chronic recording of DC potential changes  together with its contribution to seizure initiation and termination.