Nano Lab Cross Disciplinary Feasibility Account

The complex machinery underlying biological function operates at a scale that is far smaller than traditional medical devices. However, advances in nanotechnologies for the first time allow us to fabricate sensors and electronics with dimensions compatible to cellular and sub-cellular structures, opening new possibilities for diagnosing and treating human disease. Long-standing strengths in biomedical and nanoscience research place Newcastle University in an ideal position to capitalise on these opportunities, but only if existing collaboration between the disciplines can be consolidated and new links forged. This proposal will achieve this by providing a forum for engineers, medical scientists and clinicians to present technologies, applications and patient needs, and to support scoping studies into adventurous, novel nanomedicine projects that emerge. We have identified two projects to be investigated initially: nanoscale smart card technology and nanoscale neural interfaces. Smart cards (for example chip and PIN credit cards) contain embedded electronic circuits that receive power and communicates via electromagnetic induction. In principle, such technology can be implemented in devices less than a thousandth of a millimetre in size, which could be placed inside cells within the body to sense and relay valuable diagnostic information. Neural interfaces communicate electrically with nerve cells in the body and have numerous applications for treating neurological disorders, for example as neural prostheses to restore movement to paralysed patients. However, the long-term stability of such interfaces is compromised by the tissue response to foreign bodies, caused in part by the mismatch in the scale of brain cells and the implanted wire electrodes. By incorporating nanowire features onto these electrodes we anticipate that this problem can be overcome. Both these projects potentially offer a high reward in terms of clinical application, but are high risk because the novel nanotechnologies have yet to be demonstrated in a biological setting. This proposal will allow researchers to carry out preliminary feasibility studies in support of further funding, advised by a steering panel of academics drawn from a range of specialities with strong cross-disciplinary track records. In addition, the panel will assess and allocate resources to other nanomedicine proposals arising out of our discussion forums. The overall aim is to foster a culture of cross-disciplinary interaction, enabling cutting-edge technologies to be targeted to real, unmet clinical needs.

Our initial feasibility projects address key areas of patient need: 1. Intracellular sensing: The ability to locate nanoelectronics devices inside a living cell will revolutionize research in medicine and biology. These nano smart systems may each contain an array of sensor/actuators with some silicon nanoelectronics linked with further information processing remotely. Detecting disease related molecules in cells or surrounding fluid is the basis of most diagnostic, prognostic and monitoring procedures. Potential clinical applications include cancer, inflammatory conditions, mitochondrial disease and neurodegenerative disease - in all cases access to intracellular biomarkers could be invaluable for early diagnosis leading to more effective treatment. Economic impact: This is highly speculative and may take over 10 years to reach market. However, there is no competing IP which allows the UK to take a dominant role if this idea proves feasible. It will lead to spin-outs and jobs which is strongly supported by our RDA. The nanomedicine market is predicted to reach $160B by 2015 so it is imperative that the UK gets a share. 2. Improved neural sensors: Improved chronic electrode devices for long-term sensing of neural signals have a number of clinical and research applications including: * Brain-Machine Interface technologies based on nanowire intracortical electrodes would be of great benefit to patients with motor paralysis by restoring some degree of autonomy through control of assistive devices, wheelchairs, or functional electrical stimulation. Spinal Cord Injury affects 35,000 individuals in the UK. These patients often require round-the-clock assistance; the life-time cost of care for an individual quadriplegic patient can exceed 1 million. * 'Closed-loop' neurostimulation: Intracortical recording electrodes may also have application in next-generation neurostimulation devices. Over 30,000 Parkinsonian patients have already benefited from Deep Brain Stimulators; these are now indicated for additional conditions including dystonia, tremor, depression and obsessive-compulsive disorders. However, at present stimulation is delivered in continuous trains, limiting the efficacy and applicability of treatments. 'Closed-loop' neurostimulation, in which neural activity at one site determines the spatio-temporal pattern of stimulation delivered at another, represents a logical next step in neurostimulator development. * Basic science applications: Long-term chronic recording from the cortex of experimental animals is increasingly becoming a widely-used tool in experimental neuroscience, with application in research on the mechanisms of recovery from nervous system injury and longitudinal studies into neurodegenerative disease. Economic impact: If successful this will be distributed for animal research quite quickly (~5 years) although approval for patient may take longer. Neurostimulation comprises one of the fastest growth sectors in the medical device market, and improvements in electrode designs would have many applications in this field. In order to commercialise such a product, its additional application as a research tool is advantageous providing an attractive and quickly accessible market. If the novel design features of our electrode offer new biosensing capabilities and improved long-term performance this may further increase research applications for chronic recording and open new avenues of experimentation with widespread benefits for the understanding and treatment of neurological conditions. We have very experienced technology transfer capability to exploit the results of these and other scoping activities funded by this proposal. Monthly management meetings will have a standing item on potential impact of research, and supervise the establishment of patents protection prior to any disclosure in publication.