Many chronic medical conditions can be managed by patients taking specific drugs, such as naltrexone for opioid addiction, buprenorphine for chronic pain and insulin for diabetes at specific dose levels on a regular or periodic basis. These drugs are typically delivered via oral, transdermal, or injected means. They usually follow simple first-order drug release kinetics which may pose a significant risk of either undesirable toxicity (overdosing) due to initial concentration peaks arising from burst release or loss of efficacy (underdosing) because of subsequent rapid drug concentration decline below the therapeutic range. Hence it is of great interest to pharmaceutical companies, medical device companies, patients and healthcare organizations to achieve a sustained drug release, ultimately reducing toxicity and increasing efficacy. For example, it has been found that 20 to 40 micro-gram doses of human parathyroid hormone fragment (1-34) [hPTH(1-34)] administered daily for up to two years have resulted in a decrease in the incidence of fractures associated with osteoporosis. Thanks to rapid advances in microfabrication, RF technology and materials science, implantable drug delivery (IDD) has become very appealing for many types of drug and for treating many chronic diseases. The global market for IDD was worth £9.5 billion in 2015. It is projected that the market size for IDD will increase exponentially over the next decade. IDD offers several unique advantages: i) it localizes the drug delivery, maximizing the efficacy-dose relationship; ii) it reduces toxicity and leads to fewer side effects; iii) it supports the controlled administration of a therapeutic dose at a desirable rate of delivery; and iv) it improves patient compliance by eliminating the chances of missing or erring in a dose. An IDD device can be classified as either passive or active, depending on whether there is a permanent power source on the device. Passive IDD devices are simple, but lack quantitative feedback from the implant to the external unit after implantation. Thanks to the on-board battery, active devices have higher device intelligence than passive devices. Many active IDD can continuously monitor the drug dosage and send the information wirelessly to an external reader. However, existing sensors in active IDD devices usually require a dedicated readout circuit with the sensor inside the implant, increasing the total size, cost and power consumption of the device. The proposed technology is similar to the RFID technology for which an external reader interrogates a passive LC resonator sensing tag, wirelessly acquiring the information from the sensor. It requires no battery and is not limited by the types of drug or media surround the drug.

THz microscopy lies at the interface between physics and electrical engineering, and it provides a platform for cutting-edge research and development in biology, chemistry, physics and engineering. By probing fundamentally different information about biomolecular structure and functional dynamics compared to infrared radiation and light, THz radiation promises to revolutionize spectroscopy and imaging for the life sciences. In addition, THz radiation has the advantage of being non-ionizing and very sensitive to polar substances, such as water, and provides label-free skin disease diagnosis and better image contrast for soft tissues than hazardous X-rays or optical imaging techniques. Until recently though, THz sources and detectors were very cumbersome. Hence, the widespread adoption of THz technology, let alone THz microscopy, has lagged behind microwaves, infrared and optics. Another hurdle that has held THz microscopy back is its failure to accomplish resolution below the diffraction limit with near-real-time operation, which is a feature that its optical counterpart achieved few decades ago with fluorophores. Such super-resolution and fast acquisition time features are especially critical for the life sciences whose specimens (e.g., cells) have micrometer-dimensions and are typically in continuous motion in their biological environment. The transformative THz microscope proposed in this research programme will explicitly address this problem and will achieve fast label-free super-resolution imaging not seen before at THz frequencies by combining two techniques from completely different realms: evanescent-wave illumination (used in optical microscopy and in optical fibre sensors) and synthetic-aperture collection (used in spaceborne remote sensing). To succeed in the implementation of the THz microscope, the project will have to: (i) design and fabricate new high-performance optics based on metasurfaces since conventional lenses are lossy at THz frequencies, as well as being bulky. (ii) develop efficient signal analysis and processing algorithms specific to the microscopy system to generate images with enhanced resolution at a rate that enables one to study the temporal evolution of biological samples. (iii) design the system, integrate the hardware (THz source, high-performance optics, and THz camera) and software (control and image reconstruction algorithm) and calibrate the microscope to create a turn-key system. The project will also (iv) benchmark the 0.3 THz microscope against other frequencies and imaging modalities to quantify its added value to the field of life sciences microscopy. This information will be crucial to engage with the life sciences community since THz technology is largely untapped outside the engineering and physical science communities.

Molecular communication (MC) provides a way for nano/microdevices to communicate information over distance via chemical signals in nanometer to micrometer scale environments. The successful realization of MC will allow its future main applications, including drug delivery and environmental monitoring. The main hindrance for the MC application stands in the lack of nano/micro-devices capable of processing the time-varying chemical concentration signals in the biochemical environment. One promising solution is to design and implement programmable digital and analog building blocks, as they are fundamental building blocks for the signal processing at MC transceivers. With two existing approaches in realizing these building blocks, namely, biological circuits and chemical circuits, synthesizing biological circuits faces challenges such as slow speed, unreliability, and non-scalability, which motivates us to design novel chemical circuits-based functions for rapid prototyping and testing communication systems. Conventional chemical circuits designs are mainly based on chemical reaction networks (CRNs) to achieve various concentration transformation during the steady state from the input to the output with all chemical reactions occurring in same "point" location. This kind of design does not fit for the time-varying signals in communication system due to that the temporal information can be invisible to even state-of-the-art molecular sensors with high chemical specificity that respond only to the total amount of the signaling molecules. Thus, this project aims to design the chemical reaction-based microfluidic MC prototypes with time-varying chemical signal processing functionalities, including modulation and demodulation, encoding and decoding, emission and detection. This also facilitates the microfluidic drug delivery prototype design and cancer cell on chip testing under time-varying drug concentration signal. This project has the ambitious vision to develop novel time-varying chemical concentration signal processing methodology for microfluidic MC and microfluidic drug delivery. In the long run, 1) our microfluidic MC results will enable the implementation of MC functionality into nanoscale machines, by downsizing the proposed components through the utilization of nanomaterials with fluidic properties, and by translating the functional chemistry into biological circuit designs; 2) our microfluidic drug delivery results will revolutionize the conventional drug delivery testing approach by enabling ICT technologies for novel in-vitro microfluidics for drug delivery, allowing rapid measurement of therapeutic effect, toxicology, to reduce development costs and minimize the use of animal models.

The impact of stroke incidents is immense: five million people die and another five million are permanently disabled every year due to stroke incidents, and stroke is placed third among reasons for acute death and first among reasons for neurological dysfunction in the western world. Its impact and consequences, however, are even more devastating in developing countries, where according to WHO estimates, death from stroke accounted for 85.5% of stroke deaths worldwide in 2001, and the number of disability-adjusted life years (DALYs), i.e. years of life lost and years lived with disability, was almost seven times higher than in high-income countries. In China, in particular, stroke is the leading cause of death, and it strikes earlier in life than it does in the western world. Its treatment relies to a great extent on the information provided by diagnostic methodologies, which are necessary to guide medical experts in choosing a treatment strategy and to assess its efficiency. This project will build on existing expertise by the project partners in the UK and China towards the development of a portable and low-cost system which can detect the occurrence, and monitor the evolution of stroke and its treatment using microwave technology. The proposed system will use low-power, non-ionizing radio waves (microwaves) to image the occurrence and evolution of stroke in an accurate manner, thereby removing the need for expensive imaging systems (such as CT scans) which would result in significant delays in treatment decisions. This approach can address several clinical needs. For example, the system can be used inside an ambulance to determine the type of stroke much earlier than CT scanners inside a hospital. This is particularly important for ischemic stroke patients (which account for over 80% of total cases), for which early detection is crucial for thrombolytic treatment (i.e. blood thinners that can dissolve clots in blood vessels due to ischemic stroke but would worsen the condition of a blood vessel rupture occurring in hemorrhagic stroke). Moreover, by serving as a point of care diagnostic tool for patients at their homes, the proposed approach can lead to more efficient management of stroke in the post-acute stage, which can improve the potential recovery of the patient. The scanner can therefore revolutionise stroke therapy and recovery in communities where CT or MRI equipment is scarce or not available, such as underdeveloped or rural areas in China and other ODA countries. The project will develop the microwave device relying on academic and industrial UK expertise in microwave imaging algorithms and instrumentation. In addition to offering academic expertise in microwave medical imaging, the project's ODA partners will accelerate the proposed device's pathway to clinical use through a network of hospitals and medical centres and cooperation with over 35 hospitals across 30 cities in China in the planning of clinical trials. Although delivered in China, the project can make a difference in many developing countries where stroke is emerging as a health threat also for younger populations (e.g. South Asian countries), as the targeted device will be affordable and simple enough to use.

Patients with chronic diseases must take day-to-day decisions about their care and rely on advice from medical staff to do this. However, regular appointments with doctors or nurses are expensive, inconvenient and not necessarily scheduled when really needed. Increasingly, there are low cost and highly portable sensors that can measure a wide range of physiological values. Can such 'wearable' sensors be used to improve the way that chronic conditions are managed? Patients could have more control over their own care if they wished; doctors and nurses could monitor their patients without the expense and inconvenience of visits, except when they are actually needed. Remote monitoring of patients is already in use for some conditions but there are barriers to its wider use: it relies too much on clinical staff to interpret the sensor readings; patients, confused by the information presented, may become more dependent on health professionals, whose work may be increased rather than reduced. The project seeks to overcome these barriers by addressing two weaknesses of the current systems. First is their lack of intelligence. Intelligent systems that can help medical staff in making decisions already exist and can be used for diagnosis, prognosis and advice on treatments. One especially important form of these systems uses belief or Bayesian networks, which show how the relevant factors are related and allow beliefs, such as the presence of a medical condition, to be updated from the available evidence. However, these intelligent systems do not yet work easily with data coming from sensors. The second weakness is any mismatch between the design of the technical system and the way the people - patients and professional - interact. We will work on these two weaknesses together: patients and medical staff will be involved from the start, enabling us to understand what information is needed by each player and how to use the intelligent reasoning to provide it. The medical work will be centred on three case studies, looking at the management of rheumatoid arthritis, diabetes in pregnancy and atrial fibrillation (irregular heartbeat). These have been chosen both because they are important chronic diseases and because they are investigated by significant research groups in our Medical School, who are partners in the project. This makes them ideal test beds for the technical developments needed to realise our vision and allow patients more autonomy in practice. To advance the technology, we will design ways to create belief networks for the different intelligent reasoning tasks, derived from an overall model of medical knowledge relevant to the diseases being managed. Then we will investigate how to run the necessary algorithms on the small computers attached to the sensors that gather the data as well as on the systems used by the healthcare team. Finally, we will use the case studies to learn how the technical systems can integrate smoothly into the interactions between patients and health professionals, ensuring that information presented to patients is understandable, useful and reduces demands on the care system while at the same time providing the clinical team with the information they need to ensure that patients are safe. If successful, our results will be useful not only for the examples of chronic diseases studied on the project but also for managing other chronic medical conditions, when the same techniques can be applied. Although the project will produce prototype systems, several stages of product development and clinical trials will be needed before real systems are available for patients; we will prepare for these and make a first evaluation of the economic benefits of the proposed systems during the project. Also, several technology companies are involved in the project's Advisory Board to help ensure effective commercial exploitation in the long run.