Over the last decade excellent non-invasive sensing platforms have become available for capturing real-time health and lifestyle data, with the fitbit and Apple Watch being well known examples. However, current 'wearable' sensors all have major limitations: they connect to the body using straps and similar which do not maintain a good connection over long time periods; they have high power consumptions meaning the device must be taken off and recharged, at best, every couple of days; they contribute a significant amount to electronic waste. They are thus far from realising their true potential. This challenge is recognised by the EPSRC, with 'Disruptive technologies for sensing & analysis' being a core part of the 2015 Healthcare Technologies strategy. We propose to tackle this challenge by advancing novel material manufacturing approaches to realise next generation 'conformal' sensor nodes. This will make a disruptive next generation sensor platform for the very long term monitoring of a number of body parameters (motion, electrophysiological and temperature data) which is very different to current bio-sensing approaches. Our novel manufacturing will enable sensors which are: - Mounted on a conformal substrate, attaching directly to the skin without a strap, and maintaining contact for several days at a time. - Manufactured using inkjet printing to allow minimal waste and responsive manufacturing, potentially tailoring each sensor to each person. Graphene nanoparticle based inks will replace current silver nanoparticle inks which, due to the inert nature of graphene, avoids the electronic waste issues associated with silver inks. - Tailored with new ink and substrate formulations so that both the graphene ink and conformal substrate are 'transient'. That is, they work for a period of time and then naturally decompose into safe, inert and easily removed components, enabling easy use and disposal. - 3D in nature by using 'popup' structures manufactured on pre-stressed substrates. This will allow 'actuated antennas', coupling the mechanical and electromagnetic properties of a 3D antenna in order to allow simultaneous sensing and transmission using the antenna component, significantly reducing the device size as conventional instrumentation can be removed. - Ultra low power using a novel switching strategy to allow secure digital transmission over an RFID wireless link without the need for a dedicated, high power, analogue-to-digital converter microchip. - Increased in wireless powering range, by devising reduced size epidermal antennas that exploit magnetically coupled loops in tattoo antennas with under 3 times the surface area of current approaches, reducing ink use for digital fabrication. - Optimized for robustness to motion interference, allowing the collection of high quality signals in real-world, out-of-the-lab situations. - Suitable for scale-up manufacturing with roll-to-roll and/or sheet fed printing of key elements, integrating with pick and place capabilities. - Integrated into initial complete system demonstrators which will be showcased to our partners, covering the use of long term sensor nodes with people who are elderly and with children. Collectively these represent a step change beyond 'wearable' devices available today. Our new sensors will be customisable battery-less RFID tags that can operate more than a metre from a powered reader, stay attached for many days at a time, and with a controlled lifetime set by the transient nature of the manufacturing. At this early stage we do not propose to target any one clinical application area, but rather to make the next generation of technologies for conformal on-body sensor nodes that collect longitudinal information relevant to a number of disease areas. We will work with our partners through pathways to impact activities to maximise the possibility of exposure to relevant end users in healthcare scenarios.

This multidisciplinary project will exploit an established UK based team's track record comprising RF & bio-sensing engineers, battery & materials scientists, and CPI, the UK National Catapult for Printed Electronics. Centred around Additive Manufacture and aimed towards scale-up, we will transform nascent wireless skin-based sensing to the high data rate capacity offered by upcoming communications systems using license-free 24 GHz channels. This will enable new streaming of biodata for remote diagnostics, monitoring and care, as well as ultra-low impact wireless EEG for forehead/ear/hair free regions. It will make possible the use of multiple sensing tags on multiple people simultaneously monitoring physiological parameters such as accelerometery (for activity tracking), photoplesmography (for heart rate monitoring), and sweat (for metabolite monitoring). At high data rate, this represents a step change over available technologies. Manufactured on highly flexible, potentially stretchable, substrates the skin tags take the form factor of temporary tattoos and are highly long lasting, discrete for social acceptability, and can follow the micro-contours of the skin to give a large contact surface area and consequently sensing signal-to-noise ratio. To achieve our aims, we will advance wireless mmWave devices, on-skin electronics, low-power bio-sensing, and additive manufacture. Additionally, through CPI, we will develop scale-up processes for these mmWave devices. Through existing investments the applicant team is positioning the UK for the large scale manufacture of on-skin sensor tags. EP/P027075/1 is creating an inkjet printing based manufacturing process for sensors on flexible substrates which avoids cleanrooms, uses graphene based ink formulations for biodegradability, and can be scaled up large run roll-to-roll screen printing. EP/R02331X/1 added the capability to print TiO2/LiFePO4 batteries integrated into the platform, removing a key integration bottleneck. This new proposal 'MultiSense' seeks to build upon the manufacturing base created by these two projects, extending it to overcome the key sensing limitation of current on skin tags: that they can only monitor one parameter from one person at a time, and at a comparatively low data rate. These projects are further limited to producing first principle non-elastic, low capacity integrated batteries and UHF frequency (868 MHz) RF devices which require print resolutions similar to conventional masks for wet etching (typically 200 um). Further, our experience of UHF RFID reveals transmission delays of 6 ms, and a reliable data rate upper limit of only 400 bps (corresponding to a sample rate of just 30 Hz for a modality such as accelerometry). In MultiSense, we propose to overcome these limitations by moving from RFID to 24 GHz ISM (Industrial, Scientific Medical) band transmission, where very substantial uncongested bandwidth is available, offering orders of magnitude higher bit rates than UHF. In addition, the smaller wavelengths will increase antenna miniaturisation on integrated elastic substrate batteries, requiring print resolutions of 50 um. The new batteries will be solid state and polymer based with elastic current collectors. We will also investigate the mmWave signal surface guiding over the skin as a mechanism to allow for inter-patch communications. Sensing robustness will be improved as minor variations/misplacements in the sensor positions could be captured, and potentially corrected for in software. This will impact on diagnostic EEG measurements where currently entire datasets (from cabled electrodes) might be abandoned when individual electrodes disconnect. To enable the measurement of skin-based transmission between patches with new dry electrode designs, we will work with International Research Visitor Professor Koichi Ito of Chiba university, an expert in human phantom design.

Regenerative medicine aims to develop biomaterial and cell-based therapies that restore function to damaged tissues and organs. It is a cornerstone of contemporary and future medicine that needs a multidisciplinary approach. There is a world-wide shortage in scientists with such skillsets, which was highlighted in 2012 by the Research Councils UK in their 'A Strategy for UK Regenerative Medicine" which promotes 'training programmes to build capacity and provide the skills-base needed for the field to flourish'. The major clinical need for regenerative medicine was highlighted by the Science and Technology Committee (House of Lords; July 2013), who identified that 'The UK has the chance to be a leader in [regenerative medicine] and this opportunity must not be missed', and that 'there is likely to be a £44-54bn NHS funding gap by 2022 and that management of chronic disease accounts for around 75% of all UK health costs'. Vascular diseases are the leading cause of death and disability worldwide, musculoskeletal diseases have a huge burden in pain and disability, diabetes may be the 7th leading cause of death by 2030, and peripheral nerve injuries impair mobility after traumatic injuries. There is a pressing need for commercial input into regenerative medicine. Whilst the next generation of therapies, such as stem cells and biomaterials, will be underpinned by cutting-edge biology and bioengineering, strong industrial-academic partnerships are essential for developing and commercialising these advances for clinical benefit. We have established strong industrial partnerships which will both enhance the CDT training experience and provide major added value to our industrial partners. Regenerative medicine is a top priority for the University of Manchester (UoM) which has excellence in interdisciplinary graduate training and a critical mass of internationally renowned researchers, including newly appointed world-leaders. Our regenerative medicine encompasses physical, chemical, biological and medical sciences; we focus on tissue regeneration and inflammation, engineering and fabrication of biomaterials, and in vivo imaging and clinical translation, all on our integrated biomedical campus. We propose a timely Centre for Doctoral Training in Regenerative Medicine in Manchester that draws on our exceptional multidisciplinary depth and breadth, and directly addresses the skills shortage in non-clinical and clinical RM scientists. Our expertise integrates tissue regeneration & repair, the design & engineering of biomaterials, and the clinical translation of both biological and synthetic constructs. Our centres of excellence and internationally-leading supervisors across this multidisciplinary spectrum (details in Case for Support and UoM Letter of Support) highlight the strength of our scientific training environment. Defining CDT features will be: integrated cohort-based multidisciplinary training; skills training in engineering, biomedical sciences and pre-clinical translation; imaging in national Large Facilities; medical problem-solving nature of clinically co-supervised PhD projects, including in vivo training; comprehensive instruction in transferable skills and commercialisation; outward-facing ethos with placements with UK Regenerative Medicine Platform hub partners (UoM is partner on all three funded hubs), industrial partners, and international exchanges with world-class similarly-orientated doctoral schools; presentations in seminars and conferences. In this way, we will deliver a cadre of multidisciplinary scientists to meet the needs of academia and industry, and ensure the UK's continuing international leadership in RM. Ultimately, through training this cadre of doctoral scientists in regenerative medicine, we will be able to improve wound healing, repair injured nerves, blood vessels, tendon and ligaments, treat joint disease and restore function to organs damaged by disease.