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.
Building nano-scale optical components using DNA-origami - Dr. A. Clark
Engineered metal nanostructures bridge the gap between far-field optical radiation and near-field quantum phenomena, enabling the manipulation of light below the diffraction limit. Recent advances in the production of these nanostructures has led to a new generation of photonic components with previously unattainable, non-natural optical properties. Known as optical metamaterials, complex arrangements of these nanostructures have allowed the development of novel sensors, optical cloaking technologies, and ‘flat’, two-dimensional optical elements for wave-front shaping (lenses, wave-plates etc.).
Key to the further development of metamaterial research and its use in real-world scenarios are new, scalable strategies for large-area fabrication of nano-structured optical systems. To date, “top-down” lithographic techniques such as electron-beam lithography (EBL) have dominated. However, as electronic and photonic devices shrink toward a critical fabrication limit, using DNA-directed self-assembly to perform engineering tasks could unlock a new level of fabrication complexity, with resolution, alignment, speed and scalability attributes that outstrip traditional techniques. DNA-directed nano-manufacturing therefore offers to provide a valid route between the current state-of-the-art and the next-generation of optical devices.
This PhD project will investigate the use of DNA-origami to form complex arrangements of optical nanoparticles on surfaces for the first time. Acting as ultra-high-resolution, programmable scaffolds for nanoparticle attachment, the DNA-origami will self-assemble into well-defined, pre-engineered networks covering large surface areas. The student will investigate all aspects of the system, from design of the DNA-origami to the subsequent construction of novel nano-optical devices.
The student will form part of a vibrant multidisciplinary team spanning nano-optics, DNA-engineering, advanced micro/nano lithography, and synthetic biology. Using a variety of cutting-edge tools housed within Glasgow’s world-leading James Watt Nanofabrication Centre (JWNC), the student will have the opportunity to develop the aforementioned technology and explore its use as a new biological toolset for materials engineering and optics. As such, this multidisciplinary project represents an excellent opportunity for a student with a background in either engineering, physics, chemistry or biology to work at the forefront of nanotechnology research.
New Medical Diagnostic Devices using Mobile Phones - Prof. J. Cooper
Background: Point-of-care medical testing enables patients to obtain diagnostic results that inform clinical treatment, without visiting a specialist healthcare. Within the developed world, this includes “bathroom testing” (e.g. pregnacy or sexual health) or home management of diseases (e.g. diabetes). In low and medium income countries (LMIC), the paradigm enables infectious disease testing “in-the-field” in rural areas where there is no specialized access to healthcare professionals. In either case the outcome is the same, namely new technology enabling timely and informed treatment and delivering healthcare benefits without direct access to clinical facilities.
Since their invention in 1973, mobile phones have become ubiquitous with >4.6b unique users (78% of subscriptions are in LMICs). Modern smartphones have ~14 built-in sensors including proximity, pressure, gyroscope as well as heart rate (used for the delivery of healthcare through m-health). They now also offers an attractive platform for point-of-care medical diagnostics - providing a rechargeable battery, a high resolution camera for imaging, a CPU for processing data and a means of transmitting results (to enable “decision-support” from experts or expert systems).
Novelty: Low power, ultrasonic waves can readily be created using Surface Acoustic Wave, SAWs (SAW transducers are used in every mobile phone as a filter and a duplexer). SAW are acoustic waves of nanometer amplitude and MHz frequency which, when interacting with a fluid, causes a physical displacement. We have already shown that we can use SAWs for medical diagnostics and have patented a series of new medical diagnostic technologies including enrichment of low concentrations of rare diseases, separation of blood samples and advanced DNA diagnostics. We have now also shown the SAW platform can be combined with a smartphone to allow imaging and processing of a medical sample without the need of a dedicated analyser or a PC.
Project: We will develop a novel, specific test for exploring blood disorders. The novel test will be of equal interest to home-testing in the developed world as for disease management in-the-field in LIMICs. We have collaborators both in UCLA, USA and Uganda and there is the possibility to travel and work with either or both in-country.
Candidate: The qualities required for the successful candidate will include having a very good Honours degree, a demonstrated ability to work in teams and an expertise in electronics, fluid mechanics or biomedical engineering. Excellent candidates from other disciplines such as biophysics and biomedical sciences will be considered.
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 myocardial infarcts, 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 at the treatment site for a sufficient period to allow cells to migrate to the area of injury and to proliferate and differentiate. A major roadblock to effective protein therapeutics is the lack of biocompatible and injectable carriers that deliver proteins 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. In particular, Poly(ethylene glycol) (PEG) hydrogels present minimal inflammatory reactions and excellent safety record in vivo use, and different functionalities can be easily incorporated to its structure. In addition, the low viscosity of microgel suspensions enables facile injection into the body.
In this project an innovative microfluidics-based polymerization system will be used to synthesize biocompatible hydrogel microparticles that can be loaded with a desired protein. 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 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.
This system will be initially used for bone applications, through the controlled delivery of growth factors which induce the bone formation. However, the system will may be optimized for its translation to other applications such as osteoarthritis, myocardial infarct, or tissue regeneration.
Biological inspired control for rehabilitation 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).
The aim of this interdisciplinary research is to further explore the potential of intermittent predictive control as a new paradigm for engineering and physiological control, specifically in the context of neurological rehabilitation and re-learning. The project aims to develop novel rehabilitation approaches, based on neuro-prostheses and rehabilitation robotics, by using biological insights gained from understanding human control and how it achieves real-time flexibility and the ability to learn and adapt to new and changing environments.
Our long standing clinical research link with the Scottish National Spinal Injuries Unit provides a basis for experimental evaluation of these concepts in a clinical setting.
The successful applicant should have a background in biomedical engineering and / or control engineering, and an interest in interdisciplinary research involving human physiology and motor control.
The role of mechanotransduction in cancer metastasis and treatment - Prof. N Gadegaard
Cancer is the change in cell growth from a normal to an uncontrolled situation. A common consequence of a malignant cancer is the ability of the cells to migrate from the primary site to a new location. This process is known as metastasis and involves the cells migrating through the tissue where they may enter the blood stream. Many of the cancer drugs on the market are used to target cell migration and motility, e.g. Paclitaxel, Rho and Rock inhibitors, thus limiting the spread of malignant cells. As biological cells migrate in the body, they exert force on their environment. The magnitude of such forces is in the nanonewton range and can be measure in vitro (in a Petridish) in various ways.
Some of the early experiments from the literature used particles embedded in a soft material. By tracking the movement of the particles and using the knowledge of the substrate’s mechanical properties, the forces could be calculated. There are some drawbacks in the use of this system such as uneven distribution of particles and varying mechanical properties due to the synthesis. As an alternative, substrates have been designed to present a bed of regularly spaced soft pillars on which the cells are migrating. This significantly eases the tracking of the pillars. Another relevant factor is that by changing the dimensions of the pillars it is possible to engineer a range of different mechanical properties from the same substrate material. This is relevant to mimic changes in the tissue mechanics as a consequence of cancer growth.
In this project, the aim is to manufacture such micropillars and study the forces from different cancer cell types and compare them to healthy cells. Together with the force tracking, the influence of different inhibitor and cancer drugs will be studied to investigate the relationship between cells' migration patterns and force distribution to the different pathways being influenced by the drugs and inhibitors. The successful candidate will receive training in both cell biology and engineering. This will include cell culture & staining, microscopy and image analysis from the biological part of the project. In Engineering, the candidate will receive training in our nanofabrication facilities which will enable the candidate to engineer different model systems for the force tracking.
Controlling Synthetic Biology Systems with Acoustics for Biomedicine - Dr. J. Reboud
Synthetic biology is a cross-disciplinary field using engineering and biological principles to design and construct new biological pathways and systems that do not exist in nature. It offers the promise of new drugs with targeted therapies, ‘green’ fuels and new methods for environmental remediation. Systems are generally created by assembling “constructs” or components within living cells (e.g. bacteria) that require an external control to trigger their functionality. Traditionally, this has relied on small biochemical molecules - greatly limiting both the range and implementation of the systems developed.
We are interested in using external forces, such as those propagated by light and sound, to control the implementation of synbio constructs within both living cells and artificial cells. The latter application will use cell-free expression systems to avoid the constraints of toxicity, growth, and escape mechanisms inherent in their living counterparts, which have limited the potential of synbio to create truly novel molecules (which for example could be useful but toxic to the living chassis it is manufactured in). Using our expertise in microfluidics, we aim to develop platforms to rapidly develop new constructs and test for their efficiency, thus rapidly leading to application.
Another potential strand of application for the platform could lead to the control of living systems using acoustics, for example through the control of gene expression with ultrasound, in a similar way as light can be used in optogenetics. This new technology will be based on low-cost, battery-powered devices, to enable decentralised utilisation, in developing countries.
The work is highly cross-disciplinary and we would welcome motivated microbiologists, engineers, or physical scientists. The student will develop expertise in microfabrication and acoustics to produce a platform to handle SynBio parts (DNA, expression kits, enzymes). The student will also benefit from being trained in SynBio, with our collaborators in the College of Medical, Veterinary and Life Sciences, using parts to assemble and optimise new protein and gene networks for the production of new biomedicine (such as antimalarial drugs), as well as new systems for Water Remediation.
Protein-based hydrogels to engineer disease models - Prof. M. Salmeron-Sanchez
This is a multidisciplinary project that will make use of novel hydrogels that combine proteins with synthetic materials to be used in state-of-the art 3D printers to engineer in vitro tissue models.This technology has the potential to be applied to understand a range of pathological and physiological conditions at the cellular and tissue level.
The remit of the PhD spans from cancer research to regenerative medicine going through stem cell differentiation and cell/material interactions. We intend to engineer systems in vitro that recapitulate the architecture and cellular organisation of target tissues.
The final project will be decided in dependence of the interest of the applicant, providing some flexibility to pursue your own research interests. The supervisory team is very interdisciplinary and it links with a range of national and international collaborators that will contribute significantly to the training and development of the PhD candidate.
Bioactive Biodegradable Composites for 3D Printing - Prof. KE Tanner
Three dimensional (3D) printing is a powerful tool for the manufacture of tailor made implants, including biomedical devices and implants, with accelerating worldwide application. However, the currently available 3D feedstock materials are plain polymers. While they are biocompatible and degradable, so acceptable in biomedical applications, they have low mechanical properties and are not bioactive, so sub-optimal for loading bearing bony applications. The aim of this project is to develop composite feedstock materials using degradable polymers reinforced with either hydroxyapatite and/or tricalcium phosphate. These calcium phosphates are related to bone mineral and thus have biological activity, are either degradable or non-degradable in vivo and can adsorb proteins. The composite feedstock would allow the 3D printing of load bearing bioactive scaffolds or devices.
Optimisation of the manufacturing process will based on the size, shape and relative amounts of the reinforcing phase with the aim of increasing both the stiffness and strength of the manufactured 3D implants and to provide the required degradation rate for specific applications. The aim is to produce a material that is bioactive and capable of significant load bearing.
The PhD student will be exposed to materials characterisation processes, composite production techniques, in vitro bioactive testing and mechanical testing under physiological conditions. The materials characterisation will cover both the pre-cursor materials and the composites, before and after degradation studies. The materials characterisation techniques will include optical and scanning electron microscopy, Fourier transform infra red spectroscopy (FTIR), TGA etc. Thus the student will be exposed to a large range of techniques as well as being part of a multi disciplinary group. The produced material will feed into cell culture studies thus providing further opportunities for exposure to additional characterisation methods.
Machine learning, EEG based prediction of central neuropathic pain - Dr. A. Vuckovic
The aim of this PhD is to create a decision system, capable of predicting a risk factor for developing central neuropathic pain in patients with spinal cord injury. That will enable identifying patients who would benefit from preventive treatments of pain.
Central neuropathic pain is a frequent consequence of spinal cord injury. Pain is an unpleasant but useful sensation, which gives us a warning that something went wrong with the body. Central neuropathic pain is however a false, ‘phantom’ body alarm, created in the central nervous system (spinal cord and brain), which feels like it is coming from the body, i.e. arms or legs. Although it is caused by an injury to the spinal cord, it may develop months, or even years, after the injury has healed. Once it has developped, it is extremely hard to treat, as standard pain killers do not work. Currently it is very hard to predict who will develop pain, therefore there are no preventive treatment.
In our previous research, we have shown that brain activity measured by electroencephalography (EEG) looks different in a group of patients who eventually developed pain compared to a group of patients who did not. This project will go a step further, to create a predictor of pain for a single person rather than for a group. The project will also look at a yet unanswered scientific question: which EEG brain wave features are most representative of future pain ?
The project includes clinical experimental work, around EEG recording, at the National Spinal Unit in Glasgow and subsequent signal analysis, including machine learning and other similar techniques. Applicants with a strong interest, and preferably some previous knowledge, in machine learning, are welcome.
Exploring single-cell microfluidic technology for antibiotic discovery - Dr. H Yin
Widespread bacterial resistance to antibiotics has become a serious and growing threat to public health. New mechanisms continuously emerge and significantly reduce the utility of today’s antibiotics. In May 2016, bacteria resistance to colistin - the antibiotic of last resort – was observed in humans, making the discovery of new antimicrobials increasingly urgent.
In this project, we will use microfluidic technologies to screen potential antibiotic candidates to treat superbugs. This study will be built upon our expertise in the on-chip rapid quantitation of bacterial resistance under antibiotic stresses using dynamic monitoring of cell growth and morphological variations of single cells within a community. Initially, we will use known resistant pathogens, but will move to clinically relevant samples in collaboration with clinicians. Statistical analysis of the data will be preformed in collaboration with system biologists. The devices and methodologies from this project also has the potential to benefit researchers in various fields, for example, clinical nutrition, microbiology, synthetic biology and antibiotic drug development.
The student will gain a wide range of desirable skills from multidisciplinary training (microbiology, microfluidics and statistics). These include opportunities to gain expertise in state-of-the-art micro- & nano-fabrication, image analysis, and other instrumentation skills that are desirable in both the academic and industrial sectors. The project would be suitable for candidates with a background in physics, chemistry or an engineering topic with a strong interest in microbiology.