When bioelectronic devices such as cochlear implants, bionic eyes, brain-machine interfaces, nerve block stimulators and cardiac pacemakers are implanted into the body they induce an inflammatory response that is difficult to control. Metals used historically for these types of devices (for instance platinum/iridium in cardiac pacemakers) are both stiff and inorganic. Consequently these implants are tolerated by the body rather than integrated and the device is often walled off in a scar tissue capsule. As a result high powered and unsafe currents are required to activate tissues and produce a therapeutic response. This limitation has prevented the development of high resolution bionic devices that can improve patient quality of life (for example by enabling improved perception of sound for cochlear implant users). This research programme will bring together concepts from tissue engineering, polymer design and bionic device technologies to develop soft and flexible polymer bioelectronics. A range of novel conductive biomaterials will be used to either coat conventional devices or fabricated as free-standing fully organic electrode arrays from conductive polymers (CPs), hydrogels, elastomers and native proteins. The electrode array stiffness will be matched to that of nerve tissue and the polymer components will be biofunctionalised to improve cell interactions, prevent rejection and minimise scar formation. Coating technologies will be assessed as a pathway to modifying existing commercial devices in collaboration with industry partners, Galvani Bioelectronics and Boston Scientific. Ultimately, the research programme will demonstrate safety and efficacy of polymeric electrode arrays using protocols defined by medical device regulatory bodies. Collaboration with industry partners will ensure that outcomes are relevant to the market and directly translatable while engaging key stakeholders. Polymer bioelectronics will be a ground breaking step towards safer neural cell stimulation, which is more compatible with tissue survival and regeneration. High resolution electrode arrays based on polymer technologies will create a paradigm shift in biomedical electrode design with tremendous impact on healthcare worldwide.

TRANSFORMATIVE RESEARCH VISION We aim to create a platform of wirelessly networked therapeutic implants which are powered by harvesting energy from the body's own energy supply: glucose. The use of energy harvesting will allow for much smaller implants with much easier surgical implementation, and thus much wider use. The ability of multiple implants to reliably communicate with each other will allow for new types of personalised medical therapies. In particular, it will allow for tuning of the therapeutic interventions according to sensed information from across the body. CLINICAL APPLICATION SPACE Across the world, societies are rapidly ageing, so a key challenge is to ensure healthy optimal lifespans for as many as possible. Drug therapies have been improving, but it can be difficult to optimally modulate or tune the body's function to the normal daily cycle. So, in recent years there has been a surge of interest in bioelectronic solutions. For example, SetPoint Medical just received FDA approval (Autumn 2020) for a vagal nerve implant to treat arthritis. Here in the UK, Galvani is hoping to achieve similar success with trials already underway. Bioelectronics has many modes of operation - including pacemakers for heart, brain and body, sensory restoration (for the deaf and blind), and short-term healing applications such as supporting opioid withdrawal. The market is therefore very large, and expected to grow rapidly in the coming decades. In the first instance, we will target Cardiac Arrhythmias. WHY OUR TEAM? We have brought together a leading UK team of bioelectronic experts with knowledge in microelectronics, ultrasonic communication, micro-fuel cells, artificial intelligence, and medical device design to push this project forward. Furthermore, three of the team have direct experience in the medical technology industry, and we have separately been involved in multiple large clinical translation projects. We strongly believe we can achieve success in this high-risk, high-reward project as we have already created working pre-requisites for each of the components. WHY NOW? Bioelectronic implants have steadily been reducing in size. The Medtronic Micro cardiac pacemaker now has the diameter of a marker pen. However, further miniaturisation is difficult because implantable batteries need to be armoured. Further decreases in size will make battery capacity negligible given the minimum dimensions of the armour plate. Furthermore, existing implants act as independent entities and can only sense in their immediate vicinity. As such it is difficult, for example, to fully synchronise the left and right ventricle stimulation of the heart. Similarly synchronous stimulus of an internal organ, e.g. the liver or pancreas, according to clinical signs elsewhere in the body is currently very challenging, if not impossible. UNDERPINNING INNOVATIONS: our proposal is based on two breakthrough capabilities that we have been developing in respective labs, and are only now becoming possible: 1. GLUCOSE ENERGY HARVESTING: We are now able to harvest sufficient energy to drive a cardiac pacemaker from glucose in the body's interstitial fluid. At the core of the harvester is a fuel cell that uses metallic-nanostructured catalysts with an architecture scalable to long term operation inside the body. 2. RELIABLE ULTRASONIC INTRABODY COMMUNICATIONS: We have developed a prototype ultrasound communication scheme with in-built error correction, which can, for the first time, allow for reliable communication between disperse implants. When optimised for use in intrabody networks, our system will allow for dispersed sensing and intelligence not currently possible.

Our vision is to rejuvenate modern electronics by developing and enabling a new approach to electronic systems where reconfigurability, scalability, operational flexibility/resilience, power efficiency and cost-effectiveness are combined. This vision will be delivered by breaking out of the large, but comprehensively explored realm of CMOS technology upon which virtually all modern electronics are based; consumer and non-consumer alike. Introducing novel nanoelectronic components never before used in the technology we all carry around in our phones will introduce new capabilities that have thus far been unattainable due to the limitations of current hardware technology. The resulting improved capability of engineers to squeeze more computational power in ever smaller areas at ever lower power costs will unlock possibilities such as: a) truly pervasive Internet-of-Things computing where minute sensors consuming nearly zero power monitor the world around us and inform our choices, b) truly smart implants that within extremely limited power and size budgets can not only interface with the brain, but also process that data in a meaningful way and send the results either onwards to e.g. a doctor, or even feed it back into the brain for further processing, c) radiation-resistant electronics to be deployed in satellites and aeroplanes, civilian and military and improve communication reliability while driving down maintenance costs. In building this vision, our project will deliver a series of scientific and commercial objectives: i) Developing the foundations of nanoelectronic component (memristive) technologies to the point where it becomes a commercially available option for the general industrial designer. ii) Setting up a fully supported (models, tools, design rules etc.), end-to-end design infrastructure so that anyone with access to industry standard software used for electronics design today may utilise memristive technology in their design. iii) Introduce a new design paradigm where memristive technologies are intimately integrated with traditional analogue and digital circuitry in order to deliver performance unattainable by any in isolation. This includes designing primitive hardware modules that can act as building-blocks for higher level designs, allowing engineers to construct large-scale systems without worrying about the intricate details of memristor operation. iv) Actively foster a community of users, encouraged to explore potential commercial impact and further scientific development stemming from our work whilst feeding back into the project through e.g. collaborations. v) Start early by beginning to commercialise the most mature aspects of the proposed research as soon as possible in order to create jobs in the UK. Vast translational opportunities exist via: a) The direct commercialisation of project outcomes, specifically developed applications (prove in lab, then obtain venture capital funding and commercialise), b) The generation of novel electronic designs (IP / design bureau model; making the UK a global design centre for memristive technology-based electronics) and c) Selling tools developed to help accelerate the project (instrumentation, CAD and supporting software). Our team (academic and industry) is ideally placed for delivering this disruptive vision that will allow our society to efficiently expand the operational envelope of electronics, enabling its use in formidable environments as well as reuse or re-purpose electronics affordably.

Our vision is to rejuvenate modern electronics by developing and enabling a new approach to electronic systems where reconfigurability, scalability, operational flexibility/resilience, power efficiency and cost-effectiveness are combined. This vision will be delivered by breaking out of the large, but comprehensively explored realm of CMOS technology upon which virtually all modern electronics are based; consumer and non-consumer alike. Introducing novel nanoelectronic components never before used in the technology we all carry around in our phones will introduce new capabilities that have thus far been unattainable due to the limitations of current hardware technology. The resulting improved capability of engineers to squeeze more computational power in ever smaller areas at ever lower power costs will unlock possibilities such as: a) truly pervasive Internet-of-Things computing where minute sensors consuming nearly zero power monitor the world around us and inform our choices, b) truly smart implants that within extremely limited power and size budgets can not only interface with the brain, but also process that data in a meaningful way and send the results either onwards to e.g. a doctor, or even feed it back into the brain for further processing, c) radiation-resistant electronics to be deployed in satellites and aeroplanes, civilian and military and improve communication reliability while driving down maintenance costs. In building this vision, our project will deliver a series of scientific and commercial objectives: i) Developing the foundations of nanoelectronic component (memristive) technologies to the point where it becomes a commercially available option for the general industrial designer. ii) Setting up a fully supported (models, tools, design rules etc.), end-to-end design infrastructure so that anyone with access to industry standard software used for electronics design today may utilise memristive technology in their design. iii) Introduce a new design paradigm where memristive technologies are intimately integrated with traditional analogue and digital circuitry in order to deliver performance unattainable by any in isolation. This includes designing primitive hardware modules that can act as building-blocks for higher level designs, allowing engineers to construct large-scale systems without worrying about the intricate details of memristor operation. iv) Actively foster a community of users, encouraged to explore potential commercial impact and further scientific development stemming from our work whilst feeding back into the project through e.g. collaborations. v) Start early by beginning to commercialise the most mature aspects of the proposed research as soon as possible in order to create jobs in the UK. Vast translational opportunities exist via: a) The direct commercialisation of project outcomes, specifically developed applications (prove in lab, then obtain venture capital funding and commercialise), b) The generation of novel electronic designs (IP / design bureau model; making the UK a global design centre for memristive technology-based electronics) and c) Selling tools developed to help accelerate the project (instrumentation, CAD and supporting software). Our team (academic and industry) is ideally placed for delivering this disruptive vision that will allow our society to efficiently expand the operational envelope of electronics, enabling its use in formidable environments as well as reuse or re-purpose electronics affordably.

We propose to build the EPSRC Centre for Doctoral Training in Sensor Technologies for a Healthy and Sustainable Future (Sensor CDT) on the foundations we have established with our current CDT (EPSRC CDT for Sensor Technologies and Applications, see http://cdt.sensors.cam.ac.uk). The bid falls squarely into EPSRC's strategic priority theme of New Science and Technology for Sensing, Imaging and Analysis. The sensor market already contributes an annual £6bn in exports to the UK economy, underpinning 73000 jobs and markets estimated at £120bn (source: KTN UK). Major growth is expected in this sector but at the same time there is a growing problem in recruiting suitably qualified candidates with the necessary breadth of skills and leadership qualities to address identified needs from UK industry and to drive sustainable innovation. We have created an integrated programme for high quality research students that treats sensing as an academic discipline in its own right and provides comprehensive training in sensor technologies all the way from the fundamental science of sensing, the networking and interpretation of sensory data, to end user application. In the new, evolved CDT, we will provide training for our CDT students on themes that are of direct relevance to a sustainable and healthy future society, whilst retaining a focus that delivers value to the UK economy and academia. The 4-year programme is strongly cross disciplinary and focuses on sustainable development goals and emphasises training in Responsible Innovation. One example of the latter is our objective to 'democratise sensor technologies': Our students will learn how to engage with the public during research, how to play a valuable part in public debate, and how to innovate technology that benefits society. Technical aspects will be taught in a bespoke training programme for the course, that includes lectures, practicals, lab rotations, industry secondments, and skills training on key underpinning technologies. To support this effort, we have created dedicated, state-of-the-art infrastructure for the CDT that includes laboratory, office, teaching, and social spaces, and we connect to the world leading infrastructure available in the participating departments and partner industries. The programme is designed to create strong identities both within and across CDT cohorts (horizontal and vertical integration) to maximise opportunities for peer-to-peer learning and leadership training through activities such as our unique sensor team challenges and the monthly Sensor Cafés, attended by representatives from academia, industry, government agencies, and the public. We will create a diverse and inclusive atmosphere where students feel confident and empowered to offer different opinions and experiences and which maximises creativity and innovation. We have attracted substantial interest and support (>£2.5M) from established industrial partners, but our new programme emphasises engagement also with UK start-ups and SMEs, who are particularly vulnerable in the current economic climate and who have expressed a need for researchers with the breadth and depth of skills the CDT provides (see letters of support). We recruit outstanding, prizewinning students from a diverse range of disciplines and the training programme connects more than 90 PIs across 15 departments and 40 industrial partners working together to address future societal needs with novel sensor technologies. Technology developers will benefit through connection with experts in middleware (e.g. sensor distribution and networking, data processing) and applications experts (e.g. life scientists, atmospheric scientists, etc.) and vice versa. This integrative character of the CDT will inspire innovations that transform capability in many disciplines of science and industries.