New generation of biosensors using nanopore extended Field Effect Transistors (NexFET)

Biosensors are an integral and increasingly important part of modern life sciences and new developments in biosensor technologies are increasingly seeing their application in the process industry, security, environmental and biodefense application markets. We seek to address the limitations of current diagnostics and we propose the development of a radical new nanotechnology for high throughput electronic recognition of neurotransmitters. While there are some moves to develop nanotechnology approaches to biosensing, these have yet to make a mark and there remains an unmet need in the development of lab-on-chip biosensors that are affordable, integrated, fast, capable of multiplexed detection and monitoring, and crucially, highly selective which can detect trace levels of analyte in biological fluids. This proposal directly addresses these issues. This will be achieved by designing a new class of nanoscale FET sensors dubbed NexFET (nanopore extended Field Effect Transistor) that combine the advantages of nanopore single molecule sensors, FET's and recognition chemistry.

EPSRC's strategy states that it wishes to encourage new ways of thinking, develop new tools and stimulate further investigation in bioscience, medicine and environmental sciences within UK industry and other parts of government such as the NHS. A wide array of important biological and clinical problems exist that could be addressed with such bionanosensors. These include the study of cell growth, differentiation, migration, viral entry, immune system function and signal transduction involved in aging, cardiomyopathy, neurodegeneration, and cancer. Most of these processes involve biologically relevant molecules in cells and their environments. Thus the generation of nanosensors to measure these biological molecules in real time with high sensitivity and accuracy is potentially extremely valuable. The proposal contributes towards the EPSRC areas of Analytical Science, Diagnostics and Healthcare Technologies, and especially in the context of development of novel tools, methods, and technologies in the physical and biological sciences. It will provide the basis for a novel, easy to use, robust and inexpensive sensor technology, for the detection of neurotransmitters and proteins in-vitro in biological fluids.

This project will deliver an unprecedented advance in single-molecule, label-free sensing that will contribute substantially to the UK's global leadership in this area. The major outputs will be (i) a step-change in the development of new analytical and biophysical tools and (ii) interdisciplinary training for early-career researchers. (iii) This proposal also contributes to the current EPSRC Strategic Research Priority of Technology development for the biosciences. We anticipate that this will benefit policymakers, funding bodies and academic institutions by providing clear evidence of the value of interdisciplinary research for the future of UK science.

This proposal will lead to direct impact in a number of different areas:

Communications and engagement. All parties have strong commitments to knowledge exchange. The results of these studies will be published in top journals, after filing of any patents to protect the IP. In particular, we will present at biophysical, scanning probe and also medical meetings to ensure that those working in this area are aware of these advances in the field.

Academic Collaborations: the applicants on this grant all have numerous academic collaborators both within our institutions and worldwide, who can both provide input into and benefit from this research. Additionally, the radical nature of this research proposal provides an opportunity to seek new collaborations and industrial partners. A collaboration has recently been established with Prof David Dexter (Division of Brain Science, ICL) and he has agreed to contribute his expertise and clinical samples. He has 30 years of experience in the field of understanding the pathological mechanisms involved in the development of PD and the development of novel therapeutics through in-vitro and in-vivo animal models and clinical trials. In 2002 David set up the internationally renowned Parkinson's UK Tissue Bank where clinical samples (both brain and CSF). Other collaborations will be established with groups that have interests in nanoscale sensors for clinical applications (e.g. Prof Minjun Kim, Drexel University, and Prof Jaebum Choo, Hanyang University).

Industrial Collaborations: the radical nature of this research proposal provides new opportunities to develop both existing and potentially new collaborations with industrial partners. Related to this proposal, YK and DK have co-founded Ionscope Ltd which has and will result in efficient knowledge transfer especially related to objective 4 of this proposal. JBE and AI have strong links with Raith Technologies GmbH and Siemens Healthcare in Germany and Hitachi in Japan.

Transferable skills: the training provided to the researcher, on this project will increase the availability of highly skilled workers in the UK that will be an advantage in a knowledge-based economy. In addition, it will also lead to enhanced skills and knowledge for the leading academics that will inform their ability to progress the future development of this project.