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健康问题，尽管由于持续的人口变化，情况预计会恶化，但我们对根本原因的了解仍然非常有限(正如200多项治疗或预防阿尔茨海默病的失败临床试验所突显的那样)。因此，至关重要的是，通过提供适合于在分子和细胞层面上应对关键挑战的新技术方法，进一步推动我们目前的研究努力，从而加深我们对这些毁灭性条件的理解。由于高透明度和导电性等优异的材料特性以及微制造技术的最新进展，基于石墨烯的设备在克服研究技术挑战方面显示出巨大的潜力，预计将使研究人员能够在细胞和分子水平上进一步了解疾病的进展。该项目旨在通过独特的集成全透明、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LED，以及培养用于电生理和光学量化的以光遗传为中心的疾病表型，来调查各种疾病情况。在洁净室环境中初步制备了合适的基于石墨烯的微电极阵列(GMEA)，并对其进行了详细的电学性能分析，以及它们在石墨烯界面与附近液体环境之间的复杂相互作用，该项目打算将这项技术与最先进的体外疾病模型(如肌萎缩侧索硬化症(ALS))和其他与体内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融合在肉瘤中(FUS)蛋白的作用的理解，最近发现FUS蛋白在包括ALS在内的各种神经退行性疾病以及一般衰老和健康恶化中具有重要意义。该项目不仅在神经退化方面具有很高的相关性，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了解，而且还具有促进测试和开发合适的药物或治疗方法的范围，同时进一步促进社区努力促进将石墨烯设备用于生物医学应用(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).