Possible research topics to be undertaken in the Biomedical Engineering Division of the School of Engineering are given below. If you are interested in any of these projects, you should email the prospective supervisor associated to the chosen topic for discussing your intentions (see contact details by following the topic link).
Alternatively, you are welcome to identify a different project topic within any of our research areas and email your project proposal to the Head of Division, Prof Manuel Salmeron-Sanchez (Manuel.Salmeron-Sanchez@glasgow.ac.uk), who will direct you towards a prospective supervisor with expertise in that area.
DNA Origami as a nano-engineering tool - Dr. A. Clark
The term DNA Origami refers to the folding of a long DNA strand into complex geometric shapes using a number of shorter DNA strands. Powered by Watson-Crick base-pairing, the final ‘shape’ of the DNA Origami structure is programmable; altered by changing the sequences of the DNA strands involved.
Once formed, it is then possible to attach inorganic nanoparticles (metals, semiconductors, etc.) to the origami structure via further DNA interactions. What makes this particularly exciting is that the DNA origami structure (and therefore the inorganic materials attached to it) is self-assembled at sub-nanometre resolution that far outstrips what is possible using traditional nano-engineering techniques.
As a result, there is significant potential to use DNA Origami as a nano-engineering tool to create new materials and devices that would otherwise not be possible.
In this project, the student will have the choice to explore the use of DNA Origami in a variety of different applications areas, including nano-photonics, self-assembling nano-materials, energy harvesting, bio-sensing, and metamaterials.
This multidisciplinary, collaborative project represents an excellent opportunity for a student with a background in either bio-engineering, physics, chemistry or biology to work at the forefront of nanotechnology research.
New advanced medical imaging technologies - Pr. J. Cooper
Background: Imaging and microscopies underpin both clinical diagnosis and basic biomedical research, studying disease processes, tissue regeneration and development.
Challenges: Our group is interested in developing new microscopy techniques to both increase the amount of information generated, but also reduce the cost and need for technical expertise. One current challenge involves developing new forms of microscopy that are able to determine the spatial location of biomarkers of diseases, such as arthritis, deep within the body to analyse the resulting structural changes within tissue and bones, which also include new therapeutic methods for restoration of organs and bone (e.g. stem cell differentiation).
A second challenge is to be able to perform advanced microscopy on low-cost, low-power platforms. Together with our collaborator Professor Ozcan (UCLA, USA), we have developed a new method that uses acoustic forcing of liquid samples to create optical components such as lenses directly within the sample. This allows us to integrate complex lens-free holography microscopy onto a mobile phone platform.
Projects: We aim to develop new imaging tools to
- probe deep into hard and soft tissues using highly innovative application of Raman spectroscopy. This will allow us, for the first time, to study non-invasively and quantitatively, the dynamics of biological processes at a molecular level, in real time. Such a tool will be used in the study of disease as well as during the regeneration of bone during therapy for example.
- Harness the interactions between sound and light, where acoustic fields are able to shape light wavefronts and allow a step-change in performance, from super-resolution to large field of view for example. These concepts will in turn enable to detect micro and nano-particles (such as viruses and bacteria) in biological fluids, thus enabling rapid diagnostics at the point-of-care (and in the field) on mobile phones.
Candidate: These projects are is highly interdisciplinary, involving the integration of approaches and methods traditionally found in Engineering, Physical Sciences and the Life Sciences. Consequently, it may, for example, suit candidates with an interest in microscopy and optics, instrumentation photonics.
Collaborations: During the PhD, the student will be encouraged to collaborate with colleagues in The Beaston Cancer Research Centre. We are also part of an international network of researchers including partners in NUS Singapore, Beijing Institute of Technology, Johns Hopkins USA, UCLA, Toronto and Harvard, providing the successful candidate with the opportunity to travel.
Microfluidics-generated microgels for therapeutic protein delivery - Dr. C. Gonzalez-Garcia
Controlled delivery of proteins is a highly promising strategy to treat pathological conditions, including bone defects and skin lesions, as well as inflammatory, metabolic and neurological disorders. Carriers are often used to increase the retention of specific biological molecules, such as growth factors, at the treatment site for a sufficient period to allow cells to migrate to the area of injury and tostimulate cellular growth and differentiation, and drive regeneration. A major roadblock to effective protein therapeutics is the lack of biocompatible and injectable carriers that deliver proteins locally with high bioactivity and suitable release rates.
Hydrogels, highly hydrated cross-linked polymer networks, have been studied as promising protein carriers due to their high water content, soft consistency, high porosity and biocompatibility. We use an innovative microfluidics-based polymerization system to synthesize biocompatible hydrogel microparticles that can be loaded with the protein of interest. The release rate of the encapsulated proteins will be controlled by the size of the particles and hydrogel network density, and the protease-dependent cleavage of hydrogel crosslinks in the case of degradable hydrogels; thus, this system provides a tuneable set of parameters for controlling release kinetics. Moreover, the microfluidics technique has the potential to significantly improve current methods to control the delivery of biological molecules due to the advantage of producing homogenous population of microgels in an efficient way. These pre-formed microcarriers can be envisioned to be simply injected into the body through minimally invasive surgery.
This system will be initially used for bone applications, through the controlled delivery of growth factors which induce bone formation. However, the system will may be optimized for its translation to other applications such as wound healing and tissue regeneration.
Biological inspired control and machine learning for clinical rehabilitation and engineering systems - Dr. H. Gollee
Explaining how humans control movement and posture has been of interest to scientists and engineers for a long time, with controversy remaining about the exact nature of human motor control, and how this is related to their ability to adapt and to learn. One approach which has been developed in recent years, is based on a combination of open-loop predictive control and intermittent closed loop control, termed intermittent predictive control (see http://www.icmm.org.uk for more details). Questions which we currently investigate include mechanisms for human-like adaptation and learning, the role machine learning can play in an adaptive intermittent control structure, and the potential of intermittent control to improve joint human-machine interaction, for example for users with special needs.
We are further aiming to apply the insights into human control gained from these theoretical developments in rehabilitation approaches, primarily based on neuro-prostheses (using electrical muscle stimulation). Since rehabilitation is a process of relearning, understanding how humans learn provides a solid basis for designing novel rehabilitation approaches. We have a long standing clinical research link with the Queen Elizabeth National Spinal Injuries Unit in Glasgow as part of the Scottish Centre for Innovation in Spinal Cord Injury (http://www.scisci.org.uk), providing an excellent basis to evaluate these concepts in clinical experiments. Applications include abdominal electrical stimulation to support respiratory function, optimisation of stimulation parameters using novel patterns, and ultrasound imaging of muscle for functional diagnosis and optimisation of interventions.
The successful applicant should have a background in biomedical engineering and / or control engineering, and an interest in interdisciplinary research involving control engineering and human physiology.
Developing organs-on-a-chip using nanofabrication and AI - Prof. N Gadegaard
The research group is combining nanofabrication technologies with computer based models to design next-generation biomaterials. The computational power available today has enabled us to make use of more complex computing science tools such as machine and deep learning. These tools can be used in an automated fashion to extract detailed information from microscopy images but can also be used to design better and smarter biomaterials. Using data from image analysis and molecular biology, the datasets can then be used to establish computational models for biomaterial design and physiological function for the desired target tissue/organ.
The research group extensively use the James Watt nanofabrication Centre to manufacture the nanoscale materials for the biological experiments. There is a rapidly growing demand to develop more physiological tools and models for drug testing. The majority of the tools available today are not realistically recapitulating the in vivophysiology of the human body. With the knowledge gained from our computer models and biological experiments, we develop the microphysiological environments to support different organs or tissues, e.g. immune system, liver, pancreas, fat or muscle. These are key organs in drug testing as well as understanding a number of vascular, metabolic or diabetic conditions. We develop the organs with local and international collaborators using using human induced pluripotent stem cells (hiPSC).
Projects exemplars (but not exclusive):
- High-content image analysis using machine and deep learning algorithms
- Developing AI and deep learning computer models for nanoscale biomaterials design
- Using information from computer models to design optimal environments for organs-on-a-chip
Using Technology to Overcome Barriers - Dr. M. Hersh
Personal Assistant and Virtual Environment for People on the Autistic Spectrum
Many autistic people experience barriers to participation in employment, education and social activities on account of the incomprehensible expectations and social behaviour of non-autistic people. The project will carry out innovative research to develop a personal assistant which, for instance, acts as an interface with other people and provides advice and explanations of a variety of social situations. It will also develop a virtual environment, including multi-player games, provide the possibility of investigating and learning strategies for complex social situations in a way that is free of consequences and risks.
Flexible Communication System
Communication is important for all aspects of life. Existing communication systems for non-verbal people have a fixed capacity and lack the potential to support the development of communication abilities. When users outgrow their existing system they are rarely provided with more advanced systems. The project will develop a flexible communication system on a mobile device for non-verbal people. In particular the system communication options will expand as the user's communication ability develops. It will have the potential to develop from a simple pictorial system through various intermediate stages to a sophisticated system able to communicate complex ideas. This will support the user in developing communication skills and open greater possibilities of interaction and participation.
Smart Mobile Travel and Environmental Information Systems for Blind, Visually Impaired and Deafblind People
This project will develop a contextual travel assistant for blind people as an app on a smart phone. Features will include points of interest information about particular facilities on the route e.g. shops, cafes; navigation to facilities; 'ocation of public transport stops, stations and pedestrian crossings; and Real time information about timetables, travel delays and roadworks. The project will involve an investigation of the travel experiences and behaviour of blind people and their requirements, and designing and testing mobile apps.
Cell characterization and separation using microfluidics for biomedical applications - Dr. M. Jimenez
Devices with channels the size of a human hair – namely microfluidic devices - can be manufactured using specific techniques (e.g. standard photolithography). Such devices have the unique ability to allow a precise control of fluids and biological cells at the micrometer scale (blood cells, bacteria etc are typically in the 1-20µm size range). Due to their small size, low price and easy manufacturing, microfluidic devices have attracted the interest of academics and industries for a wide range of applications.
Our research lies at the interface of engineering and biology; we focus on microfluidics for characterizing biological cell morphological (size, shape) and mechanical (deformability) properties. We then use these properties to design, test and optimize new devices to separate cells of interest for downstream analysis. For example, in a previous project we characterized cells in drinking water and engineered a small, easy-to-use microfluidic device - see picture below- that could remove > 95% of harmful waterborne pathogens solely based on their size (more details in this article). Our current projects open for PhD applications will use a similar approach for:
- the separation of bacteria from clinical samples to quickly detect infectious diseases in patients,
- the separation of parasites causing neglected tropical diseases to better understand their mode of transmission to humans.
More information on our research available on this website.
Keywords: microfluidics, particle separation, pathogens, biomedical
Modelling and Simulation in Drug Discovery and Drug Delivery - Dr. S. McGinty
In recent years, there has been move away from the testing of drugs in static 2D in vitro cell culture systems. More realistic systems that include dynamic flow and 3D structures of cells are increasingly being utilised due to the need to devise in vitroassays that are more predictive of in vivo behaviour. Such systems have the potential to significantly speed up drug development and lower the exorbitant costs involved with bringing a new drug to the market.
We are interested in developing modelling and simulation tools to help understand how cells respond to the varying mechanical, biological and chemical cues introduced in these more complex systems and to guide experimental protocols for drug testing in a variety of application areas including liver toxicity testing and parasitology.
We are also interested in better understanding the performance of devices which deliver drugs. Examples include drug-eluting stents for the treatment of coronary heart disease, therapeutic contact lenses for relieving eye problems and transdermal patches for delivering medication to the skin. We are interested in developing modelling and simulation tools to help understand why some devices fail; to more rationally design new drug delivery devices; to provide guidance to clinicians and; to assist with the regulatory approval process.
Robust machine learning for autonomous agents - Dr. B. Porr
Point-of-care, low-cost medical diagnostic technologies for low-resource settings - Dr. J. Reboud
Background: Creating Lab-on-a-Chip and biosensing devices for low-resource settings is an exciting new area of science. Applications encompass both diagnostics at home or the GP clinic in the UK, as well as in poor rural populations globally. The subject involves the use of advanced manufacturing technologies to produce accurate, sensitive and robust devices to detect and diagnose infectious diseases. The devices have a series of additional demands, requiring that they are easy to use, readily disposable and have minimal or no power requirements.
We have two particular interests:
- in creating ‘sentinel devices’ that are able to monitor multiple diseases in a specific area in a multiplexed format
- in informing personalised treatment by analysing drug resistance, which is becoming a crucial burden on the global scale.
Projects: We have developed two main technologies to overcome current limitations in ease of use and cost. One is linked to acoustics, via the use of surface acoustic waves to drive microfluidic manipulation of reagents on a disposable surface. With the help of advanced metamaterials and a mobile phone platform, we aim to integrate all complex manipulations involved in DNA-based assays onto a single device. We have already demonstrated this capability in detecting malaria, for which the analytical challenge lies in having the capability of measuring a single parasite-infected cell in a drop of blood, which might itself contain more than one million non-infected blood cells (by analogy, looking for a needle in a haystack). We work closely with parasitologists and epidemiologists who have field experience, working in rural Africa.
The second technology is based on paper. Paper is a cheap platform to develop advanced detection tools, which can be disposed by burning after use, making it ideal for low and high-resource scenarios. We have developed a platform based on the folding of paper matrices, akin to ‘origami’, to integrate molecular biology processing steps (DNA extraction, amplification, detection) into a single low-cost device. This platform was validated on clinical samples for the detection of malaria in Uganda, including speciation, an important factor for drug resistance.
Candidate: The work is cross-disciplinary and we are equally interested in motivated microbiologists, engineers, parasitologists or physical scientists. The student, regardless of background, will learn advanced manufacturing methods and will train in analytical sciences. There will be many opportunities to interact with our collaborators working in parasitology.
Advanced dynamic materials for stem cell engineering - Prof. M. Salmeron-Sanchez
We are interested in engineering materials that recapitulate the properties of the Extracellular Matrix (ECM) to control stem cell phenotypes. Specific projects will be around designing novel systems that combine synthetic materials with proteins and growth factors that are responsive to external stimuli, such as light. Making materials responsive and switchable would add significant advantages over current static cell engineering strategies as would allow better, more precise - temporal control, of material properties (such as mechanical properties) to modulate stem cell responses. Another line of research, within this theme is the combination of synthetic biology and genetic engineering with biomaterials. We are interested in designing living materials, based on genetically engineered non-pathogenic bacteria that can respond to external triggers and provide stem cells with different stimuli at different time points.
Specific projects can be designed in dependence of the interests of the PhD candidate. For example, similar strategies can be used to control other types of cells (e.g. cancer or immune cells). All projects can incorporate state-of-the art technologies to engineer 3D microenvironments such as microfluidics and 3D bioprinting.
Keywords: biomaterials, extracellular matrix, growth factors, cell engineering, synthetic biology, genetic engineering.
Innovative Microrheology Against Cancer (I-MAC) - Dr. M. Tassieri
Fascin1 is an actin bundling protein whose overexpression has in recent years been systematically linked to increased metastasis and poor outcome in cancer patients. Previous human studies have demonstrated that fascin1 is upregulated in many epithelial cancers. However, the underlying mechanisms governing the interactions between actin and fascin1 are still poorly understood.
Microrheology is a branch of rheology (the study of the flow of matter), but it works at micron length scales and with ‘micro-litre’ sample volumes; hence, essentials for biomedical studies. Their success relies on the fact that they can be considered as ‘exceptionally’ sensitive tools (able to resolve pN forces and nm displacements, with high temporal resolution - down to a few μsec) matching the range of sensitivity required to study a myriad of biological processes. Moreover, microrheology measurements can be performed in situ in an environment that cannot be reached by conventional rheology, e.g. inside a living cell.
The aim of the PhD project is to gather new insights on the yet not fully understood actin-fascin1 molecular interactions by means of an enhanced set of microrheology techniques. This will involve both in vitro and in vivo microrheology investigations of the actin-fascin1 rheological properties and their variations in response to drugs. This will be achieved through the generation of a wealth of new microrheology data thanks to an effective analytical method developed by Tassieri et al. [New J. Phys. 14, 115032 (2012)] that significantly improves the outcomes of microrheology methods.
The student will have the opportunity to build up an interesting academic curriculum, experiencing a multidisciplinary project supported by experienced scientist working at The University of Glasgow and from the high quality of the infrastructures already existing within the Division of Biomedical Engineering.
Brain Computer Interface for Neurorehabilitation and Neuromodulation - Dr. A. Vuckovic
Brain Computer Interface (BCI) technology provides information about brain activity in real time and translates that activity into actions of a computerised system. BCI can be used for communication, to control computer application or environment through brain activity. However BCI can also be used to train brain to work in a certain way (neuromodulation) as a part of a therapy or improvement of cognitive and motor functions in heathy people. BCI based neurorehabilitation is used for restoration of lost motor and sensory functions, caused by spinal cord injury and stroke.
The BCI group offers PhD projects ranging from applications for healthy, fit people to applications designed for patients. Research laboratories are available both at the University and at the Queen Elizabeth University Hospital, facilitating clinical applications.
Applicants can chose from a list of projects below or can propose their own project in the area of BCI.
BCI with functional electrical stimulation for restoration of motor function
Patient self-managed BCI therapies
Neurofeedback therapies for neuropathic pain
Neurofeedback therapies for improved concentration and memory
“Neurodoping” of healthy people for improvement of motor or cognitive functions
BCI games for single and multiple users (healthy people or patients)
Machine learning strategies for BCI and quantitative EEG analysis
Quantitative EEG for early detection of neuropathic pain
BCI and neuromarketing.
Engineering or computing background is desirable though candidates with other background may also apply to discuss topic which would suit best their skills and aspirations.
Interfacing fluorescent nanosystems and biology for imaging, sensors and diagnostics - Dr. W. Peveler
Dr. William Peveler
Diagnostics and imaging have become central to the fundamental understanding of the living world and the pursuit of personalised medicine to improve treatment regimens and prolong life. The use of fluorescence as a tool in these grand challenges has become deeply embedded, thanks to the promise of high sensitivity and specificity. Therefore, a continuing search is taking place for ever brighter, more stable and more versatile fluorophores that can meet the needs of researchers and clinicians.
Fluorescent nanoparticles are an attractive class of fluorophore for bioimaging and sensing, thanks to their stable and bright emission, and versatile surface chemistry. Examples include quantum dots, polymer dots and metal nanoclusters; and to realise such nanoparticles full potential, their surface must be modified to enable controlled interactions with the biology of interest.
This research will develop new, multifunctional surface coatings for fluorescent nanomaterials and apply the materials generated in next generation sensors and imaging techniques. Suitable small molecules and polymers will be synthesised, applied to the nanoparticles, and interfaced with proteins and nucleic acids to add biological specificity. The fluorescent materials will then be applied in tests for biomarkers of cardiac disease, liver fibrosis and transplant failure; and incorporated into near-patient diagnostic tools with clinical and industrial partners. There will also be the potential to interact with biomedical collaborators to incorporate the new materials into cell and animal models for imaging.
The student will work to design, synthesise and characterise the fluorescent nanoparticle systems, and then link them to biomolecules of interest with collaborators in Chemistry (Dr Andrew Thomson) before incorporating them into assays and tests with colleagues in Biomedical Engineering. The work is at the interface of the chemical, material and biological sciences and candidates with a strong background in and enthusiasm for any of these topics are encouraged to contact Dr Peveler.
Engineering “organ-on-a-chip” platforms for cancer diagnosis and treatments - Dr. H Yin
Background. Metastasis is well known as a common cause of cancer associated mortality. It is a multi-step process, involving invasion of cancer cells from the primary tumour into surrounding tissues, including into blood vessels, and transport throughout the body into distant tissues, to form secondary tumours 1. To metastasize, cancer cells have to alter their physical and mechanical properties in order to invade through different extracellular environments. In-depth understanding of key contributors to these changes will facilitate early diagnosis of cancer and identify potential drug targets to block cancer cell dissemination.
To investigate this process, we have developed a suite of tools in the past years. Examples include advanced atomic force microscopy technology to measure cell stiffness and cell-ECM interactions 2, microfluidic platforms to study confined cell migration (akin to migration in dense tissue), and biomimetic fabrication of microstructured tissue constructs 3. These platforms in conjunction with advanced “omics” studies by collaborators at the Beatson cancer institute, have led to a series of discoveries in cancer invasion 4,5,including the association of cell stiffness with cell invasion and a number of key regulators that can be potential drug targets.
Project. To further explore these discoveries for developing effective treatments, this project aims to develop a more close-to-in-vivo 3D system, namely an organ-on-a-chip platform to capture key characteristics of the multistage process of cancer invasion. This will build upon our current microfluidic 3D printing and advanced imaging technologies. The platform will allow a holistic study of the role of cell mechanics in key stages of metastasis, such as breaking from the primary tumour, entering the biomimetic blood network and migrating in the flow. Furthermore, this platform will be exploited to evaluate the delivery and efficacy of the potential drug candidates targeting the key regulators identified in our previous studies.
The work is cross-disciplinary and we are welcome motivated engineers, material scientists and cell biologists. The student, regardless of background, will learn advanced manufacturing methods, imaging analysis and other analytical sciences. The student will also work closely with Professor Jim Norman’s team at the Beaston Cancer Institute.
1. Hanahan D. et al. Hallmarks of cancer: the next generation. Cell, 2011,144, 646.
2. Chim, Y. et al. A one-step procedure to probe the viscoelastic properties of cells by Atomic Force Microscopy. Sci Rep. 2018, 8, 14462.
3. Wei, D. et al. Continuous Fabrication and Assembly of Spatial Cell-Laden Fibers for a Tissue-Like Construct via a Photolithographic-Based Microfluidic Chip. ACS Applied Materials & Interfaces 2017, 9,14606.
4. Hernandez-Fernaud, J.R. et al. Secreted CLIC3 drives cancer progression through its glutathione-dependent oxidoreductase activity. Nat. Commun. 2017, 8, 17.
5. Clarke, C.J. et al. The initiator methionine tRNA drives secretion of type II collagen from stromal fibroblasts to promote tumor growth and angiogenesis Curr Biol. 2016, 26, 755.