Microtransistores de grafeno: una tecnología de amplio ancho de banda para registrar los potenciales del campo cerebral

Eduard Masvidal Codina

José A. Garrido Ariza Antón Guimerà Brunet

Los registros de actividad neuronal de alta densidad son vitales en la investigación centrada en el descubrimiento de los procesos subyacentes a las funciones y patologías cerebrales complejas; tienen aplicaciones en el diagnóstico médico, el pronóstico y la monitorización del tratamiento, y constituyen la base de las neuroprótesis sanitarias. Sin embargo, las tecnologías actuales de registro electrofisiológico no cumplen todos los requisitos de una interfaz neuronal robusta y de alta fidelidad. En particular, una limitación actual de las matrices de microelectrodos, debido a la reactividad electroquímica de los materiales o a la alta impedancia, es la dificultad para medir la actividad infralenta (ISA, ≈ < 0,1 Hz), importante en estados fisiológicos y patologías como el daño cerebral o la epilepsia. En esta tesis doctoral, se han desarrollado interfaces neuronales flexibles basadas en transistores de grafeno (gSGFET) y se ha estudiado su uso para el registro de actividad neuronal comparándolas con las tecnologías de vanguardia actuales. Los resultados obtenidos demuestran que la tecnología gSGFET supera las limitaciones de los registros pasivos actuales de microelectrodos para el registro ISA. También se demuestra la compatibilidad de la tecnología gSGFET con las neurotecnologías actuales, como la optogenética y las técnicas de imagen cerebral. En general, la tecnología gSGFET desarrollada está madura y lista para su adopción en laboratorios de investigación, con un potencial especial para la investigación básica y preclínica traslacional. Un mayor desarrollo tecnológico centrado en la traslación clínica de los dispositivos podría aportar a los pacientes los beneficios de una mejor monitorización de la fisiología cerebral.

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.