Monolayer Graphene Coating of Intracortical Probes for Long‐Lasting Neural Activity Monitoring

Abstract

The invasiveness of intracortical interfaces currently used today is responsible for the formation of an intense immunoresponse and inflammatory reaction from neural cells and tissues. This leads to a high concentration of reactive glial cells around the implant site, creating a physical barrier between the neurons and the recording channels. Such a rejection of foreign analog interfaces causes neural signals to fade from recordings which become flooded by background noise after a few weeks. Despite their invasiveness, those devices are required to track single neuron activity and decode fine sensory or motor commands. In particular, such quantitative and long‐lasting recordings of individual neurons are crucial during a long time period (several months) to restore essential functions of the cortex, disrupted after injuries, stroke, or neurodegenerative diseases. To overcome this limitation, graphene and related materials have attracted numerous interests, as they gather in the same material many suitable properties for interfacing living matter, such as an exceptionally high neural affinity, diffusion barrier, and high physical robustness. In this work, the neural affinity of a graphene monolayer with numerous materials commonly used in neuroprostheses is compared, and its impact on the performance and durability of intracortical probes is investigated. For that purpose, an innovative coating method to wrap 3D intracortical probes with a continuous monolayer graphene is developed. Experimental evidence demonstrate the positive impact of graphene on the bioacceptance of conventional intracortical probes, in terms of detection efficiency and tissues responses, allowing real‐time samplings of motor neuron activity during 5 weeks. Since continuous graphene coatings can easily be implemented on a wide range of 3D surfaces, this study further motivates the use of graphene and related materials as it could significantly contribute to reduce the current rejection of neural probes currently used in many research areas, from fundamental neurosciences to medicine and neuroprostheses.

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

“…In addition, there were no significant differences between both implant and non-operated eyes. These findings are consistent with a high biocompatibility of graphenebased electrodes as previously suggested with in vitro studies (Bendali et al, 2013;Convertino et al, 2018), and in vivo studies (Bourrier et al, 2019). However, future works should assess neuronal function to demonstrate further the biocompatibility of the graphene material although this assessment is particularly difficult in blind animals with a flat electroretinogram (Pinilla et al, 2005;Orhan et al, 2015).…”

“…Previous cell culture studies have already demonstrated the high biocompatibility of CVD graphene bounded to a hard material (glass) for retinal neurons (Bendali et al, 2013) as well as investigated its effect on peripheral neurons (Convertino et al, 2018). Additionally, CVD graphene coated onto intracortical probes that were chronically implanted in mice cortex showed that that the presences of graphene had reduced the local density of astrocytes and microglia at the implanted site (Bourrier et al, 2019). Following graphene transfer on soft biocompatible polymer material, the in vivo biocompatibility of graphene in the retina was shown here.…”

“…Because tissue reactions can be very cell specific, there are few studies evaluating the biocompatibility of graphene in the central nervous system. It has been previously shown that single layer graphene is capable of promoting an improved neurite growth and adhesion for retinal ganglion neurons compared to glass (Bendali et al, 2013) and that primary hippocampal neurons has a significantly better adherence to graphene compared to insulating polymers as well as CVD diamond in the absence of poly-Llysine (Bourrier et al, 2019). However, no in vivo study has been completed to show a chronic biocompatibility of graphene in the ocular environment.…”

Advanced Metallic and Polymeric Coatings for Neural Interfacing: Structures, Properties and Tissue Responses

“…Furthermore, few studies focused on the tissue response to graphene coatings in vivo and the correlative effects on the detection efficiency and time reliability of neural electrodes [ 165 , 166 , 167 ]. The work from Bourrier et al indicated that the proliferations of astrocytes and microglia were significantly reduced around the monolayer graphene-coated probes after 5 weeks of implantation, suggesting that graphene was associated with the reduction of the tissue response due to its flexibility and function as a diffusion barrier [ 168 ]. Moreover, graphene was also able to enhance the neuronal differentiation of human neural stem cells (hNSCs).…”

Neuron‐Gated Silicon Nanowire Field Effect Transistors to Follow Single Spike Propagation within Neuronal Network

“…[26] These pioneering experiments paved the road for further implementation of SiNW-FETs at the manufacturing scale, to provide prototypes for various bioapplications, including cancer diagnostics, or detection of DNA, virus, bacteria and biotoxin, explosive gas, protein, nuclei acid for health and security. [27] In comparison with the emerging graphene field effect transistors (G-FETs) that provides several biosuitable properties such as excellent neuronal affinity in vitro [28] and in vivo, [29] high sensitivity, and optical transparency, [30] the silicon technology keeps two main advantages: the spatial resolution [%10 nm vs 10 μm for SiNW-and G-FETs, respectively] and the CMOS compatibility that enables large-scale implementation (at manufacturing level) with a mature technology. Nanoscale sensing has been reported with G-FETs, [31] but controlling sensing sites' location is technologically challenging.…”