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

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).

Our main impacts will be:
- a new generation of interdisciplinary nano researchers with expertise across science and innovation, fluent in the combination of approaches and technologies
- strategic developments in the study and control of nano-interfaces connecting complex architectures, for advances in emerging scientific grand challenges across vital areas of energy, health and ICT
- integration of new functional nanotechnologies together by harnessing nano-interfaces within larger application systems, and their translation into innovative products and services through our industry partners and student-led spin-outs
- a paradigm change of collaborative outlook in this science and technology
- a strong interaction with stakeholders including outreach and public engagement with cutting edge nano research
- improved use of interdisciplinary working tools including management, discipline bridging and IT

Economic impact of the new CDT is focused through our industrial engagement programme, as well as our innovation training. Our partner companies include - NPL, Hitachi, Oxford Nanopore, TWI, ARM, Eight19, Mursla, Britvic, Nokia Bell Labs, IBM, Merck, Oxford Instruments, Aixtron, Cambridge Display Technologies, Fluidic Analytics, Emberion, Schlumberger, Applied Materials and others. Such partnerships are crucial for the UK to revive high value manufacturing as the key pillar to lead for future technologies. We evidence this via the large number of CDT projects resulting in patents, with their exploitation supported by Cambridge Enterprise and our Industry Partners, and direct economic impact has also resulted from the large proportion of our students/alumni joining industry (a key outcome), or founding startups including: Echion Technologies (battery materials), Inkling Cambridge (Graphene inks and composites), HexagonFab (2D materials), Simprints (low-cost biometrics), Cortirio (rapid diagnosis of brain injury).

Training impact emerges through not just the vast array of Nano techniques and ideas that our cohorts and associated students are exposed to, but also the interdisciplinary experience that accrues to all the academics. In particular the younger researchers coming into the University are plugged into a thriving programme that connects their work to many other sciences, applications, and societal challenges. Interactions with external partners, including companies, are also strong and our intern programme will greatly strengthen training outcomes.

Academic impact is fostered by ensuring strong coherent plans for research in the early years, and also the strong focus of the whole CDT on study and control of nano-interfaces connecting complex architectures. Our track record for CDT student-led publications is already strong, including 4 Nature/Science, 6 Nature Chem/Nano/Mat, 13 Nat. Comm., with student publications receiving >6000 citations in total, including 16 papers with >100 citations each and high altmetric scores. Students have also given talks and posters at international conferences and won numerous awards/fellowships for research excellence.

Societal impacts arise from both the progression of our cohorts into their careers as well as their interaction with the media, public, and sponsors. We directly encourage a wide variety of engagement, including interaction with >5000 members of the public each year (mostly pre-university) through Nano exhibits during public events such as the Cambridge Science Festival and Royal Society Summer Science Exhibition, and also art-science collaborations to reach new audiences. We also run public policy and global challenges workshops, and will further develop this aspect with external partners. Our efforts to bring societal challenges to students' awareness frames their view of what a successful career looks like. Longer term societal impact comes directly from our engagement with partner companies creating jobs and know-how in the UK.