Novel Graphene Electrode for Retinal Implants: An in vivo Biocompatibility Study

Evaluating biocompatibility is a core essential step to introducing a new material as a candidate for brain-machine interfaces. Foreign body reactions often result in glial scars that can impede the performance of the interface. Having a high conductivity and large electrochemical window, graphene is a candidate material for electrical stimulation with retinal prosthesis. In this study, non-functional devices consisting of chemical vapor deposition (CVD) graphene embedded onto polyimide/SU-8 substrates were fabricated for a biocompatibility study. The devices were implanted beneath the retina of blind P23H rats. Implants were monitored by optical coherence tomography (OCT) and eye fundus which indicated a high stability in vivo up to 3 months before histology studies were done. Microglial reconstruction through confocal imaging illustrates that the presence of graphene on polyimide reduced the number of microglial cells in the retina compared to polyimide alone, thereby indicating a high biocompatibility. This study highlights an interesting approach to assess material biocompatibility in a tissue model of central nervous system, the retina, which is easily accessed optically and surgically.This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 785219 (GrapheneCore2) and No. 881603 (GrapheneCore3). DN has received funding from the doctoral school of Cerveau, cognition, comportement (3C) of Sorbonne Université. SP was also supported by the French state funds managed by the Agence Nationale de la Recherche within the Programme Investissements d’Avenir, LABEX LIFESENSES (ANR-10-LABX-65) and IHU FOReSIGHT (ANR-18-IAHU-0001). This work has made use of the Spanish ICTS Network MICRONANOFABS partially supported by MICINN and the ICTS ‘NANBIOSIS,’ more specifically by the Micro-NanoTechnology Unit of the CIBER in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN) at the IMB-CNM

Flexible Graphene Solution-Gated Field-Effect Transistors : Efficient Transducers for Micro-Electrocorticography

Brain-computer interfaces and neural prostheses based on the detection of electrocorticography (ECoG) signals are rapidly growing fields of research. Several technologies are currently competing to be the first to reach the market; however, none of them fulfill yet all the requirements of the ideal interface with neurons. Thanks to its biocompatibility, low dimensionality, mechanical flexibility, and electronic properties, graphene is one of the most promising material candidates for neural interfacing. After discussing the operation of graphene solution-gated field-effect transistors (SGFET) and characterizing their performance in saline solution, it is reported here that this technology is suitable for μ-ECoG recordings through studies of spontaneous slow-wave activity, sensory-evoked responses on the visual and auditory cortices, and synchronous activity in a rat model of epilepsy. An in-depth comparison of the signal-to-noise ratio of graphene SGFETs with that of platinum black electrodes confirms that graphene SGFET technology is approaching the performance of state-of-the art neural technologies

Flexible Graphene Solution-Gated Field-Effect Transistors : Efficient Transducers for Micro-Electrocorticography

Brain-computer interfaces and neural prostheses based on the detection of electrocorticography (ECoG) signals are rapidly growing fields of research. Several technologies are currently competing to be the first to reach the market; however, none of them fulfill yet all the requirements of the ideal interface with neurons. Thanks to its biocompatibility, low dimensionality, mechanical flexibility, and electronic properties, graphene is one of the most promising material candidates for neural interfacing. After discussing the operation of graphene solution-gated field-effect transistors (SGFET) and characterizing their performance in saline solution, it is reported here that this technology is suitable for μ-ECoG recordings through studies of spontaneous slow-wave activity, sensory-evoked responses on the visual and auditory cortices, and synchronous activity in a rat model of epilepsy. An in-depth comparison of the signal-to-noise ratio of graphene SGFETs with that of platinum black electrodes confirms that graphene SGFET technology is approaching the performance of state-of-the art neural technologies

Graphene based electrodes for retinitis pigmentosa diagnosis

Resumen del trabajo presentado al 4th Scientific Meeting of BNC-b Students (JPhD), celebrado en Bellatera (España) del 6 al 7 de junio de 2019.Peer reviewe

Transparent single layer graphene electrodes for electroretinogram recordings

Resumen del trabajo presentado al MRS Fall Meeting and Exhibit, celebrado en Boston, Massachusetts (USA) del 1 al 6 de diciembre de 2019.This work has received funding from the European Union’s Horizon 2020 research and innovation programme under Grant Agreement no. 732032 and the FIS2017-85787-R project financed by the Spanish Ministerio de Ciencia, Innovación y Universidades, the Spanish Research Agency (AEI) and the European Development Fund. The ICN2 is funded by the CERCA programme / Generalitat de Catalunya. The ICN2 is supported by the Severo Ochoa Centres of Excellence programme, funded by the Spanish Research Agency (AEI, grant no. SEV-2017-0706)

Interfacing neurons on carbon nanotubes covered with diamond

A recently discovered material, carbon nanotubes covered with diamond (DCNTs) was tested for its suitability in bioelectronics applications. Diamond shows advantages for bioelectronics applications (wide electro chemical window and bioinertness). This study investigates the effect of electrode surface shape (flat or three dimensional) on cell growth and behavior. For comparison, flat nanocrystalline diamond substrates were used. Primary embryonic neurons were grown on top of the structures and neither incorporated the structures nor did they grow in between the single structures. The interface was closely examined using focused ion beam (FIB) and scanning electron microscopy. Of special interest was the interface between cell and substrate. 5% to 25% of the cell membrane adhered to the substrate, which fits the theoretical estimated value. While investigating the conformity of the neurons, it could be observed that the cell membrane attaches to different heights of the tips of the 3D structure. However, the aspect ratio of the structures had no effect on the cell viability. These results let us assume that not more than 25% of cell attachment is needed for the survival of a functional neuronal cell

hBN encapsulated liquid-gated graphene field-effet transistors: toward sensitive and stable sensors in liquid medium

Resumen del trabajo presentado a la Grenoble-Barcelona twin conference: From quantum systems to new materials and smart electrical energy (GreBa-QME), celebrada en Grenoble (Francia) del 23 al 25 de octubre de 2019

Assessment of carbon contamination in MoS2 grown by MOCVD using Mo(CO)6 and (CH3-CH2)2S precursors

Resumen del trabajo presentado al 4th Scientific Meeting of BNC-b Students (JPhD), celebrado en Bellatera (España) del 6 al 7 de junio de 2019.Peer reviewe

Graphene based materials for ultimate neuroelectronics

Resumen del trabajo presentado al 2nd International Workshop Graphene Industry – Challenges & Opportunities, celebrado en Barcelona (España) el 13 de diciembre de 2016.-- et al.Neuroelectronic devices are powerful tools to study neural networks activity and to develop neural prostheses. After two decades of investigation and exploitation, the current technologies are about to reach their limit both for fundamental neural investigation and for clinical applications. Thus, important refinements are now needed to fulfill the demanding requirements associated to these applications, such as low invasiveness, long term efficacy as well as large number of recording/stimulating sites. Graphene-based materials belong to the few new material platforms that can be used to reach these ambitious targets. Indeed, graphene and graphene-based materials combine biocompatibility, easy integration in microdevices and CMOS technology, flexibility, and high electronic performance. Further, if integrated together with complementary 2D semiconductor electronic technology, graphene sensors could eventually enable the production of ultimately flat neuroelectronic devices. In this presentation, I will discuss our latest technology developments to record electrical activity in cell cultures as well as in vivo brain activity on rat cortex.Peer reviewe

Single and Multisite Graphene-Based Electroretinography Recording Electrodes: A Benchmarking Study

Electroretinography (ERG) is a clinical test employed to understand and diagnose many retinopathies. ERG is usually performed by placing a macroscopic ring gold wire electrode on the cornea while flashing light onto the eye to measure changes in the transretinal potential. However, macroscopic gold electrodes are severely limiting since they do not provide a flexible interface to contact the sensitive corneal tissue, making this technique highly uncomfortable for the patient. Another major drawback is the opacity of gold electrodes, which only allows them to record the ERG signal on the corneal periphery, preventing central ERG recordings. To overcome the limitations of metal-based macroscopic ERG electrodes, flexible electrodes are fabricated using graphene as a transparent, flexible, and sensitive material. The transparency of the graphene is exploited to fabricate microelectrode arrays (MEAs) that are able to perform multisite recording on the cornea. The graphene-based ERG electrodes are benchmarked against the widely used gold electrodes in a P23H rat model with photoreceptor degeneration. This study shows that the graphene-based ERG electrodes can faithfully record ERGs under a wide range of conditions (light intensity, stage of photoreceptor degeneration, etc.) while offering additional benefits for ERG recordings such as transparency and flexibility.J.d.l.C. and D.N. contributed equally to this work. This project received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement nos. 881603 (GrapheneCore3). This work was within the project FIS2017-85787-R funded by the “Ministerio de Ciencia, Innovación y Universidades” of Spain, the “Agencia Estatal de Investigación (AEI),” and the “Fondo Europeo de Desarrollo Regional (FEDER/UE).” Support was also provided by the French state funds managed by the Agence Nationale de la Recherche within the Programme Investissements d'Avenir, LABEX LIFESENSES (ANR-10-LABX-65) and IHU FOReSIGHT (ANR-18-IAHU-0001). The ICN2 is supported by the Severo Ochoa Centres of Excellence program, funded by the Spanish Research Agency (AEI, grant no. SEV-2017-0706), and by the CERCAProgram/Generalitat de Catalunya. E.d.C. acknowledges the Spanish MINECO Juan de la Cierva Fellowship JC-2015-25201. This work made use of the Spanish ICTS Network MICRONANOFABS partially supported by MICINN and the ICTS “NANBIOSIS,” more specifically by the Micro-NanoTechnology Unit of the CIBER in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN) at the IMB-CNM. J.d.l.C. would like to thank Laura García for the work on the images and figures throughout the whole paper writing process. E.d.C acknowledges the grant RYC2019-027879-I financed by MCIN/AEI /10.13039/501100011033. The project leading to these results have received funding from “la Caixa” Foundation (ID 100010434), under the agreement LCF/PR/HR19/52160003. These activities are co-funded with 50% by the European Regional Development Fund under the framework of the ERFD Operative Programme for Catalunya 2014–2020 with the support of the Department de Recerca i Universitat (GraphCAT 001-P-001702)