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.
Graphene, the atomically-thin honeycomb carbon lattice, is a highly conducting 2D material whose exposed electronic structure offers an ideal platform for chemical and biological sensing. Its biocompatible, flexible and chemically inert nature associated with the lack of dangling bonds, offers novel perspectives for direct interfacing with biological molecules. Combined with its exceptional electronic and optical properties, this promotes graphene as a unique platform for bioelectronics. Among the successful bio-integrations of graphene, the detection of action potentials in numerous electrogenic cells including neurons has paved the road for the high spatio-temporal and wide-field mapping of neuronal activity. Ultimate resolution of sensing ion channel activity can be achieved with neural interfaces, and it was shown that macroscale electrodes can record extracellular current of individual ion channels in model systems, by charging the quantum capacitance of large graphene monolayer (mm2). Here, we show the field effect detection of ion channel activity within neuron networks, cultured during several weeks above graphene transistor arrays. Dependences upon drugs, reference potential gating and device geometry confirm the field effect detection of individual ion channel and suggest a significant contribution of grain boundaries, which provide highly sensitive nanoscale-sized sensing sites. Our theoretical analysis and simulations demonstrate that the ion gating of a single grain boundary in liquid affects the electronic transmission of the whole transistor channel, resulting in significant conductance variations. Monitoring the ion channels activity is of great interest as most of neurodegenerative diseases relied on channelopathies, which rely on ion channel abnormal activity. Thus, such highly sensitive and biocompatible neuro-electronics which open the way to FET detection at the sub-cell precision should be useful for a wide range of fundamental and applied research areas, including brain-on-chip, pharmacology, and in vivo monitoring or diagnosis.
Supplementary video 1. Freely-moving recordings. This video shows freely-moving implanted animal during the recordings (26 experiments per probe and per week).
Monolayer graphene directly presented on the wound bed is assessed for its healing properties using both in vitro and in vivo models. For in vivo study, a cutaneous excisional wound is created on the dorsal surface of healthy and type-1 diabetic mice to mimic acute and delayed wound healing, respectively. A pig model is also chosen for its resemblance to human skin. Photographic and histological assessment of the wound are coupled with thermographic data recorded with an infrared camera. Graphene monolayer accelerates early phases of wound healing in vivo in every tested model. Upon removal of the bandage, wounds coated with graphene are less prone to temperature drop compared to the control samples. We hypothesize that graphene may directly shorten the inflammatory phase and/or enhance angiogenesis and cell migration in proliferative phase as demonstrated in vitro. Thermographic assessment of wounds could be of particular interest to follow both phenomena in an objective, rapid and non-invasive manner.
In article number 1801331 by Cécile Delacour and co‐workers, an innovative coating method is reported to wrap intracortical probes with continuous graphene monolayers, in order to investigate its impact on the bioacceptance of the implants. Experimental evidence shows that the graphene coating significantly lowers the immune response and enhances the performance and the durability of the probes, paving the way for long‐term reliable recordings of individual motor neurons.
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