Bionanofabrication Suite

This strategic equipment proposal is for a new class of instrument, a Bionanofabrication suite, to link together the worlds of precision devices with that of biomolecules and drugs to make new classes of biomedical devices.
The world of electronic equipment has been revolutionised by the precise fabrication techniques of the semiconductor industry. In the past electrical circuits were hand assembled from discrete highly variable electrical components. The advent of microfabrication techniques first enabled the robust combinations of components to make integrated devices such as transistors and amplifiers. Continued development of processes has led to the current advanced state where we each carry a super-computer in our pockets - we just call it a mobile phone.
This proposal seeks to enable the same transformation for biomedical measurement and therapy delivery devices. From the patient perspective, the devices used to measure molecular biomarkers of disease or injury are largely unchanged over the last 20 years. Blood or other body fluid samples are taken, processed in a central laboratory or maybe in the ward and the results logged in a chart. Similarly, drugs are delivered by mouth or by venous injection. Ultimately, even in intensive care measurements are made on an hourly basis. We will develop technologies to build new biomedical / bioelectronics devices that measure from cells and tissue continuously, or target therapy in a controlled way at the site of action. Potentially, we can envisage implantable devices that deliver therapy in response to the tissue signals measured by the device. This would allow truly individualised therapy.
The atom-based building and etching instruments that have been continuously refined by the modern semiconductor industry can also be used to make the sensing surfaces, channels and detectors required for a measurement device. However, current manufacturing processes run at high temperatures with a very limited range of silicon-based materials. The Bionanofabrication suite will bring together for the first time, in the same instrument, atom-based building and etching processes that are capable of running at room temperature with a wide range of final surface chemistries. The Bionanofabrication suite will operate within a quality management system, addressing an important hurdle for the early clinical testing of new medical devices.
Devices that are subsequently shown to be successful clinically, could be put into production using the fabrication techniques developed within this grant without the need for changing production methods.

The equipment requested for the Michael Uren Bionanofabrication Suite allows, for the first time within linked instruments, atomic level control of device fabrication using the biomolecules, conducting polymers and metals required for disruptive biomedical device design. This removes a major hindrance to research in therapeutic biomedical devices, and provides a route for subsequent manufacturing to support early stage clinical trials. Clinically validated devices could be manufactured at scale using the same processes.
We anticipate impacts in the following areas:
(1) New Biocompatible Fabrication Processes. This will be of direct benefit to the manufacturers of fabrication equipment, such as our partner Oxford Instruments, and indirect benefit to the growing biomedical device industry, but is likely to have spin-off benefits for manufacturers of consumer 'wellness' monitoring devices that are part of or link to smart phones.
(2) Nanoscale Delivery Systems, including nanoneedles, will enable fully dissolvable implants capable of delivering therapeutic molecules to tissue and bacteria. This will for example inhibit biofilm formation of orthopaedic implants, reducing the risk of infection and hence increasing the longevity of a patient's implant. An alternative application is to use decorated nanoneedles to both sense from and deliver factors to cells. This could allow control of phenotypic differentiation of stem cells, as part of stem cell therapies, or cell level control of bioreactors engineered by synthetic biology.. Such hybrid devices could form the basis of new manufacturing methodologies.
(3) Sensors, Devices and Actuators. Nanostructured biosensing devices will initially be built into surgical instruments giving surgeons biomolecular feedback. Early examples will include ischaemia detection via surgical clamps. Implantable biosensing devices will provide real-time feedback on the effectiveness of therapy by monitoring tissue chemistry. The benefit for patients would be adjustment of treatment dose for maximum efficacy whilst controlling side effects - a personal therapeutic index. This would have clear patient benefits for acute infection control following trauma, or during radio or chemotherapy. Ultimately coupling of nanostructured biosensing devices with drug releasing actuators would close the feedback loop and automate this process. Such approaches will be of great interest to the pharmaceutical industry as the combination of 'drug + medical device' would have great benefits for both improved drug efficacy and stronger IP protection for existing drugs.
(4) Polymer Bioelectronics. Structured polymer based electronics combined with nanowire electrophysiological contacts would provide a means of fabrication of ultra-high channel count array interfaces to the nervous system. Applications would include neuroprotheses, controlling artificial limbs, and 'electroceutics', using electrical impulses externally applied through nerve fibres to regulate organ function. Our partner Galvani Electronics is actively seeking such technologies and facilities that can produce them is a sterile, well-regulated way for pre-clinical and clinical trials.
The therapeutic bioelectronic and biomedical devices that we will create with the requested equipment are likely to have a great economic value to the UK. We have described the basis of a new manufacturing approach that is inherently scalable from device creation to full scale production. We have also directly addressed the major barrier to adoption of new technologies by the medical device industry, the need for early clinical data to justify the substantial investment required for safety and device licencing trials. This will facilitate impact through both licencing of new devices by existing medical device companies and spin-out of new companies. We anticipate that this impact will be seen in the later stages of the 5 year funding period.