Institut Néel, CNRS & Université Grenoble Alpes, 38042 Grenoble, France.
University Grenoble Alpes, CERMAV-CNRS, 38000 Grenoble, France.
Biomed Phys Eng Express. 2020 Nov 25;7(1). doi: 10.1088/2057-1976/ab42d6.
Electronic micro and nano-devices are suitable tools to monitor the activity of many individual neurons over mesoscale networks. However the inorganic materials currently used in microelectronics are barely accepted by neural cells and tissues, thus limiting both the sensor lifetime and efficiency. In particular, penetrating intracortical probes face high failure rate because of a wide immune response of cells and tissues. This adverse reaction called gliosis leads to the rejection of the implanted probe after few weeks and prevent long-lasting recordings of cortical neurons. Such acceptance issue impedes the realization of many neuro-rehabilitation projects. To overcome this, graphene and related carbon-based materials have attracted a lot of interest regarding their positive impact on the adhesion and regeneration of neurons, and their ability to provide high-sensitive electronic devices, such as graphene field effect transistor (G-FET). Such devices can also be implemented on numerous suitable substrates including soft substrates to match the mechanical compliance of cells and tissues, improving further the biocompatibility of the implants. Thus, using graphene as a coating and sensing device material could significantly enhance the acceptance of intracortical probes. However, such a thin monolayer of carbon atoms could be teared off during manipulation and insertion within the brain, and could also display degradation over time. In this work, we have investigated the ability to protect graphene with a natural, biocompatible and degradable polymeric film derivated from hyaluronic acid (HA). We demonstrate that HA-based coatings can be deposited over a wide range of substrates, including intracortical probes and graphene FET arrays without altering the underlying device material, its biocompatibility and sensitivity. Moreover, we show that this coating can be monitoredby quantifying the number of deposited charges with the G-FET arrays. The reported graphene functionalization offers promising alternatives for improving the acceptance of various neural interfaces.
电子微纳器件是监测中尺度网络中许多单个神经元活动的理想工具。然而，微电子学中目前使用的无机材料几乎不能被神经细胞和组织所接受，从而限制了传感器的寿命和效率。特别是，穿透皮层的探针由于细胞和组织的广泛免疫反应而面临高失败率。这种不良反应称为神经胶质增生，导致植入探针在几周后被排斥，从而阻止了对皮质神经元的长期记录。这种接受问题阻碍了许多神经康复项目的实现。为了克服这个问题，石墨烯和相关的碳基材料因其对神经元的粘附和再生的积极影响，以及它们提供高灵敏度电子设备（如石墨烯场效应晶体管（G-FET））的能力而引起了极大的关注。这种设备也可以在许多合适的衬底上实现，包括软衬底，以匹配细胞和组织的机械顺应性，进一步提高植入物的生物相容性。因此，将石墨烯用作涂层和传感设备材料可以显著提高皮层内探针的接受度。然而，在大脑内的操纵和插入过程中，这种单层碳原子可能会被撕裂，并且随着时间的推移也可能会发生降解。在这项工作中，我们研究了用源自透明质酸（HA）的天然、生物相容和可降解聚合物膜来保护石墨烯的能力。我们证明，HA 基涂层可以在包括皮层内探针和石墨烯 FET 阵列在内的各种衬底上沉积，而不会改变底层器件材料、其生物相容性和灵敏度。此外，我们表明，这种涂层可以通过用 G-FET 阵列量化沉积的电荷量来监测。所报道的石墨烯功能化提供了改善各种神经接口接受度的有前途的替代方案。
