Graphene Brain-on-a-Chip Platform for the Multiparametric Study of Neurodegenerative Disease

神经退行性疾病是一个全球性的健康问题，尽管由于人口结构的持续变化，情况预计会恶化，但我们对根本原因的理解仍然非常有限（正如200多个治疗或预防阿尔茨海默病的失败临床试验所突出的那样）。因此，通过提供适合解决分子和细胞水平上的关键挑战的新技术方法来进一步推动我们当前的研究工作是至关重要的，从而进一步加深我们对这些破坏性条件的理解。由于石墨烯具有高透明度和导电性等突出的材料特性，以及最近在微加工方面取得的进展，石墨烯基设备显示出克服研究技术挑战的巨大潜力，并有望使研究人员在细胞和分子水平上进一步了解疾病进展。该项目旨在通过独特的全透明、基于石墨烯的微电极阵列、超分辨率显微镜和用于靶向刺激的多功能微型led的集成，以及培养以光遗传学为中心的疾病表型以进行电生理和光学量化，来研究各种疾病状况。在洁净室环境中初步制造出合适的石墨烯微电极阵列（gmea），并对其电学能力以及石墨烯界面与附近液体环境之间复杂的相互作用进行详细分析后，该项目打算将该技术与最先进的体外疾病模型（如肌萎缩性侧索硬化症（ALS））和其他与年龄相关的神经退行性疾病)相结合。随后的生物学和生物医学研究将集中于提高我们对肉瘤融合蛋白（FUS）作用的理解，FUS蛋白最近被发现与各种神经退行性疾病（包括ALS）以及一般衰老和相应的健康恶化有实质性的关联。该项目不仅在神经退行性疾病方面具有高度相关性，旨在通过深入的调查能力在分子水平上提高我们对这些疾病的理解，而且还具有促进适当药物或治疗方法的测试和开发的范围，同时进一步促进社区努力促进将石墨烯装置用于生物医学应用（商业化）。

Neurodegenerative diseases are a global health issue, and despite the situation being expected to worsen due to the ongoing demographic change, our understanding of the root causes remains significantly limited (as highlighted by more than 200 failed clinical trials to treat or prevent Alzheimer's disease). It is, therefore, crucial to drive our current research efforts further by providing novel technological approaches suitable to address the key challenges on a molecular and cellular level and, by that, further our understanding of these devastating conditions. Thanks to outstanding material properties such as high transparency and conductivity as well as recent advances in microfabrication, graphene-based devices have shown great potential to overcome the challenges of research technology and, by that, are expected to allow researchers to gain further insights into disease progressions on the cellular and molecular level. This project aims at the investigation of various disease conditions through the unique integration of fully transparent, graphene-based microelectrode arrays, super-resolution microscopy, and versatile micro-LEDs for targeted stimulation, and the cultivation of optogenetic-centred disease phenotypes for electrophysiological and optical quantifications. Following the initial fabrication of suitable graphene-based micro electrode arrays (GMEAs) in cleanroom environments, and their detailed analysis in terms of electrical capabilities as well as their complex interaction between the graphene interface and the nearby liquid environment, the project intends to combine this technology with state-of-the-art in-vitro disease models such as Amyotrophic Lateral Sclerosis (ALS), and other age-related neurodegenerative diseases in-vivo. The subsequent biological and biomedical investigations will focus on improving our understanding of the role of Fused in Sarcoma (FUS) proteins, which have recently been identified to be of substantial relevance in various neurodegenerative diseases, including ALS, as well as general ageing and the deterioration of health accordingly. The project is not only highly relevant in terms of neurodegeneration, by aiming at improving our understanding of these diseases on a molecular level through in-depth investigation capabilities, but also has the scope for promoting the testing and development of suitable drugs or treatments, while further contributing to the communities' efforts to promote the use of graphene devices for biomedical applications (commercialisation).