Graphene microtransistors: a wide-bandwidth technology for recording brain field potentials

Eduard Masvidal Codina

Jose A. Garrido Ariza Anton Guimerà Brunet

High-density neural activity recordings are vital in research focused on uncovering the underlying processes of complex brain functions and pathologies; they have applications in medical diagnosis, prognosis and treatment monitoring and are the basis of healthcare neuroprostheses. However, current electrophysiological recording technologies do not meet all the requirements of a robust and high-fidelity neural interface. In particular, a current limitation of microelectrode arrays, due to the electrochemical reactivity of the materials and/or high impedance, is the difficulty in measuring infraslow activity (ISA, ≈ < 0.1 Hz), important in physiological states and pathologies such as brain damage or epilepsy. In this doctoral thesis, flexible neural interfaces based on graphene transistors (gSGFETs) have been developed and their use for neural activity recording has been studied by comparing them with current state-of-the-art technologies. The results obtained demonstrate that the gSGFETs technology overcomes the limitations of current passive microelectrode recordings for ISA recording. The compatibility of the gSGFETs technology with current neurotechnologies such as optogenetics and brain imaging techniques is also demonstrated. Overall, the developed gSGFETs technology is mature and ready to be adopted by research laboratories, with special potential for basic and preclinical translational research. Further technological development focused on the clinical translation of the devices could bring the benefits of better monitoring of brain physiology to patients.

for the mapping of infraslow activity and potential for clinical translation (Hartings, 2019). Although infraslow signals have been regarded as unwanted noise in the past, due to the difficulties in their measurement, there is now increasing appreciation that they reflect important neural processes that are relevant to both normal cognition and disease states, such as stroke, traumatic brain injury or epilepsy. The developed technology has high commercial interest. The intellectual property behind the fabrication methodology has been protected under an industrial secret while the methodology for obtaining wide-band high-quality recordings has been patented WO2020094898 (Guimera Brunet et al., 2018). This patent has been licensed for commercialization to a company specialized in the pre-clinical neurotechnology sector (Multichannel Systems, MCS) and is also under negotiation for licensing with a company focused on clinical translation of the technology (INBRAIN). The technology transfer performed ensures the applicability of the developed technology. Particularly, MCS is expected to launch a commercial product based on this technology in 2022, and INBRAIN foresees huge clinical potential (see letters of interest and Table 2). Moreover, further improvement and refinement of the technology is being carried out by the Graphene Flagship Core3 project. For the example, the usefulness of the technology for epilepsy research has been recently investigated(Calia et al., 2021). A project proposal to the European EIC Transition project call with participation of INBRAIN has also been submitted “Towards clinical translation of graphene-based active sensors for wide bandwidth brain mapping”. The gSGFET technology developed during the thesis is mature and will be available to be adopted by research laboratories, thanks to the commercial launch by MCS in the near future, while the human application in clinical neurophysiology is planned to be pushed by INBRAIN. Altogether, this will allow to have impact both in basic and pre-clinical neuroscience research as well as in the clinics for an improved neurophysiology monitoring.

High-Density Neural Activity Recordings; Complex Brain Functions; Brain Pathologies; Medical Diagnosis; Prognosis; Treatment Monitoring; Healthcare Neuroprostheses; Electrophysiological Recording Technologies; Robust Neural Interface; High-Fidelity Neural Interface; Microelectrode Arrays; Electrochemical Reactivity; High Impedance; Infraslow Activity (ISA); Physiological States; Brain Damage; Epilepsy; Flexible Neural Interfaces; Graphene Transistors (gSGFETs); Neural Activity Recording; State-of-the-Art Technologies; Passive Microelectrode Recordings; Optogenetics; Brain Imaging Techniques; Research Laboratories; Basic Research; Preclinical Translational Research; Clinical Translation; Brain Physiology Monitoring.