2022 Student Cohort

In this project, we aim to develop disruptive technologies that enable highly sensitive and specific disease diagnosis, using DNA or RNA signatures, to be carried out on low-cost paper-based microfluidic assay formats, for use within low-resource communities, globally. The overall vision is to translate nucleic acid testing for both infectious and non-communicable diseases onto lateral flow devices, so that they can be used without centralised laboratory facilities. We have previously pioneered paper-based DNA testing, demonstrating its application in rural low-resource settings, and in this project our aim is, working with Global Access Diagnostics, to explore manufacturing solutions, including cassette design, reagent storage and power management, to enable an integrated assay flow. By way of an exemplar assay, we will develop blood based LAMP amplification with either optical or electrochemical outputs for test results to detect schistosomiasis. Such an assay has the potential to address the public health need for schistosomiasis diagnostics that are practical for use in low-resource settings yet can match the sensitivity and specificity of more complex assays. We will explore the efficacy of devices in field studies in Uganda and/or Tanzania, working with healthcare professionals and community leaders to inform the design and operation of the assay.

Cardiovascular disease (CVD) is the leading cause of death globally. The development of grafts, which can be used to patch an injured or diseased section of artery, or replace diseased tissue entirely, are a vital treatment option for many patients.
To better understand CVD, a model is required which would allow researchers to visualise blood flow through the vascular system. This would include healthy, diseased and treated systems in order to look for markers of arterial wall shear stress and relative residence time which can indicate problems with blood flow and cell degradation.
Currently, this visualisation is performed using computer simulations, limited experimental setups and/or animal models. The aim of this PhD project is to develop an innovative, optically transparent, geometrically and physiologically representative ‘phantom’ of the human vasculature. This will involve computer-aided-design, model making, 3D printing and material characterisation. The phantom will be used to capture haemodynamics using particle image velocimetry (PIV) alongside traditional sensing technologies e.g. flow sensors.
This new model could be used in the development of new treatments, replacing animal models and supporting computational simulations. The aim is for this to be approved as a test methodology for regulatory bodies such as FDA and MRHA.

We will work with Global Access Diagnostics with a vision to produce self-powered autonomous DNA-based medical devices, bringing high performance assays into communities at the point-of-care. Key will be low-cost technologies that can be manufactured at scale, close to where they are needed most. Outcomes will involve developing innovative methods for detecting rare nucleic acid biomarker signatures in the sample, integrated with frugal digital innovations that will enable self-powered autonomous tests with digital assistance – so ensuring that the tests can be performed by non-experts. Our aim is to produce a test as simple as a pregnancy test or a lateral flow COVID test – but able to perform sophisticated highly sensitive and specific multiplexed diagnosis. The detailed work description will include combining thin film technologies with microfluidics in order to detect multiple biomarkers, as required to identify genotypes of human papillomavirus (HPV), to guide patients towards the appropriate treatment pathway in communities. The project will be carried out in close collaboration with healthcare professionals and members of the community in Senegal or Uganda, to ensure that aspects of PPIE are carefully considered and that the developments are fit-for-deployment, with the possibility of field testing in these countries.

Cell and gene therapies are poised to transform medicine by providing personalized and effective treatments for patients with chronic or life-threatening diseases. However, the complexity and high costs linked with the manufacturing of cell and gene therapy products have been severely constraining market availability and patient accessibility to these life changing therapies. There is an urgent need for innovative technologies that can address current challenges facing cell and gene therapy manufacturing. Major advances are needed in process integrated analytical tools to accurately and reliably measuring in real-time key attributes of cells throughout the manufacturing process. This interdisciplinary project aims to develop disposable, low-cost electrochemical sensor technology for real-time monitoring of cell secreted protein biomarkers. We are combining for the first time the capability to control binding on-demand using switchable receptors with screen-printing technology. Conceptually different from established biosensors where the surface immobilised affinity binding receptors act as passive probes, we introduce sensor devices, which enable active manipulation of single-domain antibodies, i.e. nanobodies. Consequently, analytes can be capture in space and time for detection, allowing the sensor devices to support real-time data capture for different periods of time. It will provide an exceptional opportunity to implement fully automated, robust cell therapy culture processes and bring down production costs, ultimately delivering cost-effective and impactful therapeutics to patients in need.

Vascular grafts have been used for over 50 years and are the established practice for the replacement of any diseased segments of aorta from the aortic valve to the iliac bifurcation. Two of the main clinical problems of these medical devices are the risk of infection and risk of thrombotic stenosis due to the material’s pro-thrombogenic activity which typically lead to new surgeries. It has been hypothesised that the lack of endothelisation of these grafts could significantly contribute to these problems. This project will develop new biomaterials with enhanced biological functionalization using growth factors and extracellular vesicles that maximize the process of endothelisation and develop next generation of vascular grafts. The project will be developed between the University of Glasgow and Terumo Aortic – a world leader in the fabrication of vascular grafts. This is a multidisciplinary project that will work at the interface between materials and cells. The project will allow the student to develop skills in a number of experimental techniques including extracellular vesicle isolation and characterization, characterisation of functional biomaterials, atomic force microscopy, confocal microscopy and cell and molecular biology at the interface between biomaterials and cells. It will also give them significant industrial exposure through close collaboration with and placements at the company.

Developing therapies and prevention strategies to tackle neurological diseases such as Alzheimer’s Disease, requires an understanding of the brain cells that are affected. Whilst extensive informative research has been conducted over the past decades using animal models, there remains a significant gap in knowledge surrounding the mechanisms underlying brain cell dysfunction. Recently, there has been a scientific revolution in the field of stem cell-derived neurons, whereby patient’s skin cells can be turned into brain cells in the lab. Bringing the biological methods together with advances in materials, artificial brain cell circuits can be produced to mimic the structure of brain tissues. Whilst stem cells provide scientists with the many different cell types as building blocks to fabricate human neuronal systems, engineering approaches need to be adopted to present these with the necessary three-dimensional complexity of human brain tissue. This project will develop a 3D biomaterial scaffold to display multiple neuro-developmental signalling factors to mimic brain architecture development.

Use of stem cells has the potential to transform regenerative medicine, if appropriate strategies can be identified for the controlled differentiation of these progenitors. One way to control stem cell differentiation in the lab is to use small signaling molecules like the synthetic steroid dexamethasone. This approach can’t generally be used in patients though, because the required drug concentrations are too high, and would lead to major side effects. We’re trying to overcome this limitation using several related methods, including developing more potent compounds, and exploring the possibility of delivering drugs directly at the site of action. We’ve got some preliminary results that look promising, and hope that you’ll join our team to help carry this work forward.

Tissue perfusion is essential in emergency medicine because it directly affects tissue viability and patient outcomes. Many clinical incidents, including heart attacks, strokes, organ transplants, and reconstructive surgical procedures such as flap surgery, may be affected by ischemia-induced cellular damage. Inadequate tissue perfusion also plays a crucial role in chronic wounds, resulting in impairments in energy metabolism, cell proliferation, angiogenesis, cytokine release, and enzyme activity, thereby impeding tissue repair. While these examples illustrate the significance of monitoring tissue perfusion, and early detection is crucial for identifying low perfusion levels to save tissues, there appears to be a clinical need for a rapid, accurate, and real-time perfusion detection approach.
This multidisciplinary research project aims to design a device for measuring the electrical characteristics of tissues, to extract a set of characteristics that accurately and uniquely correlate to perfusion levels and the onset of necrosis, and to develop an intelligent system capable of detecting these parameters in real-time. The proposed system will utilize multiple measurement modalities, such as impedance profile analysis at a broad frequency range, frequency identification for relaxation phenomenon analysis, and loss tangent analysis, to detect and analyse electrochemical biosignatures associated with tissue perfusion and necrosis. The research will first focus on electrode layouts that allow for multiplexing capabilities, the frequency range of impedance analysis determination, and evaluation to see if collected data may be enough to assess perfusion. This will address design considerations for electrodes with nanoparticles that utilize an antibody-antigen affinity mechanism for selective and sensitive detection of biomarkers linked with ischemia and necrosis. Electrochemical biosignatures will finally be incorporated into a neural network to construct an intelligent system for detecting the aforementioned conditions.
The ultimate objective of this study is to offer clinicians real-time perfusion feedback so they may make informed decisions to prevent adverse patient outcomes. This technology will have numerous clinical uses, including emergency medicine, reconstructive surgery, and chronic wound treatment.