Nanopore Sensors for Multiplexed Analysis of DNA in Clinically Relevant Samples

Nanopores have become a versatile sensing technique for the single molecule analysis of DNA, RNA and proteins. Single molecules are detected by measuring changes in ionic current flow as they pass through a nanometre scale pore separating two chambers containing salt solution. However, to advance past an initial proof of principal stage for nanopore sensing, several key areas need to be improved. This project will investigate the development of a robust nanopore sensing assay for multiplexed detection of diverse biomolecules in complex clinically relevant samples. The project will require innovation on several fronts, including redesigning and optimizing the sensing system for sensing in complex solutions, investigating benefits of functionalizing the nanopores for sensor performance, and proof of concept tests detecting and quantifying multiple biomarkers concurrently in clinical samples. The project will investigate and develop sensing protocols for counting biomarkers and genes. As the nanopore sensing technique allows for the general counting and sizing of molecules binding to DNA, the project will also aim to push the limits to use the sensors for analysing the mass of bound proteins down to sub kDa. The latter is relevant to identify protein modification and small ligand binding events and should allow for unique insights into the workings of living organisms.

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.