Indicative PhD project suggestions
The indicative project information presented on this page is intended to help prospective PhD applicants who are self funded to start a dialogue with our academic staff in an area of research that interests them. During the application process options for part funding can be explored, dependant on a number of factors, but the inclusion of an indicative project in this list does not guarantee that funding will be available.
Click on a project to see more information..
High shear mixers (rotor-stators, ultrasonicators, high pressure jets) are used for dispersion processes. Liquid-liquid dispersions (emulsification), deagglomeration (breakup of fine powder clusters) are some examples of such processes common to a wide range of industrial products from food to personal or health care. The high levels of local energy dissipation rate (close to the rotor-stator head or the sonotrode) make such devices suitable for dispersion processes. The product quality depends on both the breakup performance of these devices and the homogeneity achieved within the bulk as breakage would typically occur locally. It is also common to have significant changes in the dispersion rheology during the course of the dispersion process: a highly non-Newtonian behaviour may develop during emulsification or the delamination of layered structures or the pre-dispersion rheology, i.e. prior to deagglomeration may be complex. This would have severe effects on the overall bulk flow and hence homogeneity.
This project will aim to study the flow (flow patterns and overall homogeneity) and power characteristics of high shear mixers. The study will build on the previous work of the supervisor and make use of bench scale high shear process devices- a selection of rotor-stator designs and an ultrasonicator- in both batch and re-circulation mode. The objectives will be to establish the flow and power characteristics of such devices in liquids of a range of rheological properties and how the flow established may have an effect on dispersion processes, demonstrating this with case studies of emulsification and deagglomeration.
The knowledge developed will provide guidelines for industrial practice applicable to a wide range of products. You will have the opportunity to make use of a range of devices and analytical techniques. The knowledge and skills developed should enhance your employability in a wide range of industries.
It is anticipated that there will be the opportunity to present and discuss findings during international conferences and also network with other researchers in the field.
For further information, contact Dr Nerime Gül Özcan-Taşkın: N.Ozcan-Taskin@lboro.ac.uk
Project Ref. GOTCG035
Selected related publications:
- Özcan-Taşkın, N.G.; Utomo, A.; Cheah, A.; Alderman, N.; Gavi, E.; Padron, G.A. (2018) “Characterisation of the Delamination Process of Nanoclays” 16th European Conference on Mixing Sept 2018, Toulouse, France.
- Bacon, J.C.; Rielly, C.D.; Özcan-Taşkın, N.G. (2018) “Break up of silica nanoparticle clusters using ulrasonication” 16th European Conference on Mixing, Sept 2018, Toulouse, France.
- Yu, H.; Tsochataridou, S.; Parsons, K. ; Rielly, C.D. ; Özcan-Taşkın, N.G. (2019) Mixing studies relating to process development for new generation automotive coating formulations ECCE12, Sept 2019, Florence Italy
Process Development for New Formulation Products With Nanoparticles - Dr N G Ozcan-Taskin, Ref:GOTCG034
Products that contain nanoparticles in their formulation are finding increasing applications in a wide range of industries including the personal and health care, coatings, paints and inks, plastics due to their unique properties- greater reactivity, strength and conductivity. Some examples in current use include transparent sunscreens, packaging with superior barrier properties, reinforced rubber products such as car tyres. In order for nanoparticles to be highly functional, it is essential to achieve as fine a dispersion as possible and the dispersion should be stable for a long shelf life.
Some of these products are in the form of nanoparticulate dispersions. The manufacturing process therefore requires the incorporation of nanoparticle powders into a liquid and subsequently deagglomeration to achieve a fine dispersion. Often several process devices are used for the different stages and process design relies to a great extent on trial and error prolonging the time to market of newly formulated products. This project aims to address this approach and is aligned with the Manufacturing the Future Priority Theme of the EPSRC.
The study will build on previous work of the supervisor and make use of high shear process devices. The objectives will be to establish the effects of particle properties and hydrodynamic conditions on the kinetics of incorporation and deagglomeration.
The knowledge developed will provide guidelines for industrial practice applicable to a wide range of products. You will have the opportunity to make use of a large installation which can process 100- 200 litres, i.e. pilot to manufacturing scale as well as analytical techniques such as particle sizing, rheology, electron microscopy. The knowledge and skills developed should enhance your employability in a wide range of industries. It is anticipated that there will be the opportunity to present and discuss findings during international conferences and also network with other researchers in the field.
For further information, contact Dr Nerime Gül Özcan-Taşkın: N.Ozcan-Taskin@lboro.ac.uk
Project Ref. GOTCG034
Selected related publications:
- Özcan-Taşkın, N.G.; Utomo, A.; Cheah, A.; Alderman, N.; Gavi, E.; Padron, G.A. (2018) “Characterisation of the Delamination Process of Nanoclays” 16th European Conference on Mixing Sept 2018, Toulouse, France.
- Padron, G.A., Özcan-Taşkın, N.G. (2018) “Particle De-agglomeration with an In-Line Rotor-Stator Mixer at Different Solids Loadings and Viscosities” Chem Eng Res Des, Volume 132, p: 913-921; https://doi.org/10.1016/j.cherd.2018.01.041
- Kamaly, S.W.; Tarleton, A. C.; Özcan-Taşkın, N. G. (2017) Dispersion of clusters of nanoscale silica particles using batch rotor-stators. Advanced Powder Technology, Vol. 28, Issue 9, p: 2357- 2365 //doi.org/10.1016/j.apt.2017.06.017
- Özcan-Taşkin, N. G.; Padron, G. A.; Kubicki, D. (2016) “Comparative Performance of In-Line Rotor-Stators for Deagglomeration Processes” Chem. Eng. Sci.156 p:186–196. doi.org/10.1016/j.ces.2016.09.023
Recently biochar made from common wastes such as flower wastes, spent coffee granules, spent grain and wood waste has attracted the attention of researchers investigating water treatment as a cheaper and more environmentally-friendly alternative to activated carbon. This PhD will involve working with partners at the UK Biochar Research Centre at the University of Edinburgh to characterise standard biochars for the use in the removal of metal ions and common anions from wastewater. Pollutants for study will include heavy metals such as copper and lead, alkali earth metals such as strontium and caesium and anions such as chloride.
The findings from this study will have a wide range of applications, including waste treatment from food and drink processing, mineral processing and remediation, nuclear reprocessing and pre-desalination treatment.
In cooperation with colleagues at UKBRC, the biochar will also undergo pre and post-treatment either to vary the pore structure of the particles, or to impregnate with chemicals to modify the adsorption characteristics. A detailed study of adsorption characteristics, both in a batch system and with continuous systems, will be performed. Capacitive deionization (CDI), which has been used in water desalination and is based on the phenomenon of ion electrosorption, will be coupled with biochar adsorption with a view to study the potential of CDI in metal removal with the prepared biochar. Modelling of the lab-scale system to allow scale up to an industrial scale will also be carried out.
This project will be of interest to applicants who are interested in water treatment, environmental studies or mineral processing and provide an opportunity to apply a novel approach to some challenging problems.
Proposed by: Dr Mark Leaper Primary supervisor
Secondary Supervisor: Dr Diganta B Das
Project ref: MCLCG033
Spatial and temporal fate and transport of antibiotics in the environment and their treatment - Dr Diganta B Das and Dr Sun Tao Ref: DBDCG032
Antimicrobial Resistance (AMR) has been identified as one of the 10 threats to global health in 2019 by World Health Organization (WHO). A growing number of AMR cases indicate the high levels of antibiotics, antibiotic-resistant bacteria and antibiotic resistance genes in the environments around the world. In addressing this issue, this PhD project aims to study antibiotic fate and transport in the subsurface and its remediation potential. In effect, the PhD project aims to accomplish two sub-parts.
The first part will carry out a laboratory scale column study on a chosen antibiotic flow and transport in soil samples and estimate parameters for field scale simulation of antibiotics. With experiments at room temperature, higher temperature experiments will also be conducted to mimic environmental conditions. Flow and transport experiments will be done initially for homogeneous media, which will ensure that (a) theory can be tested and isotropic diffusion coefficients of the antibiotic is measured, (b) the experiments are being conducted correctly and no spurious results are being generated (c) results can be compared with those for heterogeneous samples. These experiments will then be conducted for various heterogeneous media, mainly, the pore size distribution and permeability of the sand samples. For higher temperature experiments (<50C), the samples will be heated indirectly (via radiation) in a heated chamber with electrical heaters. Thermal Equilibrium will be established before collecting any data.
The aim of part II is to isolate and purify bacteriophage(s), which will be amplified and used in the column experiments (in Part I) for the treatment of the antibiotic-resistant bacteria. The broad aim here is to accomplish a desired isolation of bacteriophage to destroy the antibiotic-resistant bacteria and determine treatment potential for the antibiotics. Bacteriophage will be isolated from real environmental samples, which will be explored for degradation of AMR bacteria. The gene sequences of the antibiotic-resistant bacteria obtained via next-generation sequencing techniques will be used to reconstruct the bacterial phylogeny. Media with varying concentrations of antibiotics will be used to further distinguish the antibiotic-resistant bacteria. The bacteria that could degrade certain type of antibiotics at different concentration will be identified. These bacteria will be amplified and used in column experiments to investigate their capabilities for the treatment of the residual antibiotic(s), low concentration that cannot be treated by any other methods.
It is expected that the PhD student will collaborate with our NHS-partner as well as internally with others outside the UK.
Proposed by: Dr Diganta B Das Primary Supervisor
Secondary Supervisor: Dr Sun Tao
Project ref: DBDCG032
Development of a High-Fidelity Digital Twins for a Continuous Pharmaceutical Manufacturing Process with Self-Tuning Capability - Dr Brahim Benyahia and Prof Chris Rielly Ref: BBCG031
Computational tools and model-based optimisation, control and more broadly decision-making methods and applications have grown dramatically over the last decade and opened opportunities for a new generation of digital representation and simulation tools referred to as Digital Twins. A Digital Twin provides a virtual and yet a living and interactive replica of a physical system, process or product. It offers an augmented simulation and visualisation platform and expected to become a standard capability in all industries in near future. The pharmaceutical and biopharmaceutical industries are undergoing a paradigm shift with the development and adoption of more flexible regulatory tools, agile lean and cost-effective continuous manufacturing technologies as well as robust decision-making systems. There are urgent and unprecedent needs for more reliable and predictable simulation tools for model-based design, optimisation and control which came with a real transformation of the pharmaceutical job market.
This PhD project will look at the development and validation of new strategies to build predictable high-fidelity digital twins of a continuous pharmaceutical process with self-optimising capabilities. The focus of the project will be mainly modelling and simulation but also potentially experimental validation that can be conducted by the PhD student or research collaborators. This PhD Project will benefit from our strong and well-established expertise in mathematical modelling, simulation and process control. It will also be conducted as part of the Future Continuous Manufacturing and Advanced Crystallisation Research Hub (CMAC HUB,) a world-class consortium involving more than 30 industrial and academic partners, including 8 Big Pharma companies (e.g. GSK, Novartis, Astra Zeneca, Roche, Pfizer). Initial studies would focus on a continuous crystallisation stage, but then the methodology would be extended to include downstream isolation steps, leading to a seamless fusion of physical and data-driven model implementations.
Self-funded or sponsored PhD candidates are encouraged to apply. If you do not have funding, you may still apply, however Institutional funding is not guaranteed. Outstanding candidates will be considered for any funding opportunity which may become available in the School.
Proposed by: Dr Brahim Benyahia Primary Supervisor
Secondary Supervisor: Prof Chris Rielly
Project ref: BBCG031
Digital Design of the Next Generation Resilient Modular and Sustainable Pharmaceutical Plant - Dr Brahim Benyahia, Ref: BBCG030
The COVID-19 pandemic constitutes an unprecedented challenge to the global health systems, the pharmaceutical industry all other human activities, causing severe socio-economic consequences. The most critical and visible impact on the pharmaceutical industry is undoubtably associated with the multiple shortages of pharmaceuticals experienced globally, particularly in painkillers and anaesthetic for intensive care such as Propofol and Benzodiazepines. These shortages are inherent to a surge in demand but also to production and supply chain disruptions and bottlenecks. The outbreak put the pharmaceutical organizational and production paradigms under extreme pressure highlighting many glaring weaknesses. The pharmaceutical industry has been traditionally dominated by batch processing which suffers from several disadvantages, such as long processing time, inconsistent quality and high costs. Moreover, most of the pharmaceutical plants are commonly designed for a limited number of processing steps of a single drug, or a very limited class of drugs, and operated with a set of preselected and locked operating conditions and row materials (single sourcing). The production cycle may take up to 12 months between the first synthetic step to the market release of finished drug, which usually implies the movement of materials between facilities at different locations causing unnecessary delays, supply chain bottlenecks, lengthy product testing and consequently potential shortages.
Continuous manufacturing appears as one of the most interesting options based on its proven ability to address most of the critical issues while ensuring lower production costs, greater reliability and sustainability, production flexibility and most importantly large production window. This PhD project will investigate ways to design and optimize the next generation continuous modular plants allowing for multisite sourcing, multiproduct processing, recycling, advanced automation and control as well as built-in optimal scheduling and Quality-by-Design to meet the stringent pharmaceuticals regulatory requirements. The project will develop superstructure optimisation strategies under uncertainty and contingency planning. The project may also require data collection, machine learning and multicriteria decision aiding strategies. The objective is to contribute to the development of cost-effective, flexible and agile production solutions for different classes of pharmaceuticals including generics and help address issues inherent to quality consistency during clinical trials. The project will help optimize the decision making, at early and critical stages, and expedite the development and production at scale to reduce the time between the approval of the New Drug Application (NDA) and the availability of the drug in the market. This could be particularly crucial in the case of new drug against Covid-19.
The PhD student will join an energetic research team and will interact with several PhD students working on complementary research areas. The project will also benefit from a strong research network. Self-funded or sponsored PhD candidates are encouraged to apply. If you do not have funding, you may still apply, however Institutional funding is not guaranteed. Outstanding candidates will be considered for any funding opportunity which may become available in the School.
Proposed by: Dr Brahim Benyahia
Project ref: BBCG030
Smart Filtration of Antimicrobial Agent from Drinking Water during Increased Hand-Washing Activies in Pandemic Episodes - Dr Diganta B Das and Dr Robert Edwards Ref: DBDCG029
Multi-purpose antimicrobial agent (e.g. Triclosan (TCS)), used as a common ingredient in personal care and consumer products (e.g., handwash, toothpaste) has been detected in many water bodies, but they are not treated as current methods are not designed for this purpose.
TCS’s physico-chemical properties suggest bioaccumulation and its persistence presence in the environment, and hence an increasing concern about its potential negative effects on human and animal health. Because of its partial elimination in sewage treatment plants, it is also described as one of the most commonly encountered substances in solid and water environmental compartments.
The concentration of TCS and other similar antimicrobial agents are expected to rise significantly around the world due to increased hand-washing activities during the spread of corona virus (COVID-19) and other pandemic episodes.
In addressing these points, this project will develop a smart filtration system (portable) for these compounds for drinking water. A physically based modelling tool will be used coupled with laboratory experiments on membrane filtration. The membranes to be used will be nano-porous membranes such as metal-organic framework (MOF) membranes, developed in-house or in collaboration. This project should then lead an optimised, smart filtration system to be embedded with controllers, smart wireless sensors and actuators for continuous real-time monitoring of its performance and supported by artificial (AI) data analytics and decision making in the future.
The project should be supported by a through initial literature review on the subject. It is also expected that the student will collaborate internationally with one or more of our project partners in Turkey (Selcuk University, Konya) and India (NIT, Trichy). Domestically, the PhD student will be expected to collaborate with the Institute of Artificial Intelligence, De Montford University, Leicester.
Proposed by: Dr Diganta B Das Primary Supervisor
Secondary Supervisor: Dr Robert Edwards
Project ref: DBDCG029
The sales of biopharmaceuticals and biotherapy from only Humira, Remicade, and Enbrel are over $18 billion in US in 2015. Protein therapy is expected to make about $250 billion in savings for US over the next 10 years. Manufacturing biopharmaceuticals in a cost effective and reliable route becomes a major challenge for meeting the rapidly growing demands of protein-based medicines. Moreover, the breakout diseases require fast delivery of the biopharmaceutical to the patient.
The protein crystallisation of proteins (like insulin) as one-step operation is more efficient, leading to advantages of stability storage, formulation and drug delivery.
This PhD project aims to develop innovative methods on crystallisation of (bio)pharmaceuticals, by combining (i) visual data mining: capture and analysing the visual data of crystal photos, concentration profiles, etc. and (ii) machine learning: apply the machine-learning model to correlate the crystallisation conditions (input parameters) and properties of crystals (outcomes), to optimise the crystallisation conditions and process.
The success of this project will help to accelerate the protein crystallisation process, lower the cost and increase the efficiency of the biopharmaceutical manufacturing, to solve the challenges of the breakout diseases.
This is an open call for candidates who are sponsored or who have their own funding. If you do not have funding, you may still apply, however Institutional funding is not guaranteed. Outstanding candidates (UK/EU/International) without funding will be considered for any funding opportunity which may become available in the School.
Proposed by: Dr Huaiyu Yang Primary Supervisor
Secondary Supervisor: Prof Chris Rielly
Project ref: HYCG028
Robust periodic control for optima drug regimen design - Dr Zoltan K Nagy and Dr Huaiyu Yang, Ref: ZKNCG027
In the past decade it has become evident that control system technology can have a great impact on medicine. Control technology has influenced modern medicine through robotic surgery, electrophysiological systems (e.g. pace-makers), life support (ventilators and artificial hearts), image guided therapy and surgery, and automated anaesthesia control. An important area of medicine where the application of control and systems theoretical approaches can have a strong influence is clinical pharmacology in which mathematical modelling plays a prominent role. It typically takes 15 years to bring a new drug to the market. Of every 250 compounds that enter preclinical testing, only five proceed into clinical trials, and only one will be approved by the Food and Drug Administration (FDA).
The objective of this PhD project is to develop a more accurate pharmacokinetic/pharmacodynamic (PK/PD) models of the human body by using appropriate chemical engineering principles and developing suitable analogy between chemical process unit operations and the organs, modelling their principal functionality, using a multi-compartmental mammillary modelling approach. Using the developed PK/PD models and simulations, pharmaceutical scientists can acquire an earlier understanding of the link between the physicochemical properties of drugs and the therapeutic response in the body, by better characterization of the drug’s absorption, distribution, and elimination properties. This can reduce the very high attrition rate of drug candidates by performing suboptimal candidate selection based on optimized criteria before the actual clinical trials.
A novel approach for robust optimal drug dosing control in clinical pharmacology will be designed using periodic optimistion principles and the efficiency of the approach will be demonstrated for simulated cancer therapy, diabetes and blood pressure treatment design, where personalized medical treatment can be provide significant benefits to patients.
Proposed by: Dr Zoltan K Nagy Primary Supervisor
Secondary Supervisor: Dr Huaiyu Yang
Project ref: ZKNCG027
Digital Design of Pharmaceutical Manufacturing Systems - Dr Zoltan K Nagy and Dr Huaiyu Yang, Ref: ZKNCG026
It takes from 10 to 15 years to bring a new pharmaceutical to market at a cost which rapidly approaches GBP1 billion. Many potential new pharmaceuticals fail because researchers lack reliable information about their behaviour and are unable to develop production processes which guarantee consistent product quality and stability. The principal aim of this studentship is to advance the application of systems theoretical techniques in the Pharmaceutical Engineering arena, with special emphasis on developing integrated approaches that enable engineering solid pharmaceuticals with tailor-made properties.
The main objective of the project is to develop a systematic and comprehensive framework for controlling and designing pharmaceutical crystal formation that incorporates state-of-the-art process analytical technology (PAT), statistical and first-principles models, efficient dynamic optimization and model-based control algorithms. A novel integrated quality-by-control approach will be developed, in which the crystallization process will be combined with both upstream reaction/separation and downstream process units as well as with models which describe the dissolution dynamics and bioavailabilty of the pharmaceutical in the organism, providing a framework for product design with desired downstream processing properties or tailored bioavailability. Size, shape, polymorphic form and purity of crystals will be controlled simultaneously by using a novel multi-dimensional polymorphic population balance model-based nonlinear control approach, which will incorporate the effect of impurities and solvent activities in the model. A Pharmaceutical Process Informatics System will be developed which will coordinate and combine the signals from the unique combination of sensors (PAT array) with image analysis and advanced chemometrics methods to maximize the information content, which will be used in the control algorithm.
The main mission of the project is to develop a new emerging research field of Pharmaceutical Systems Engineering, which will provide a comprehensive framework for the development of novel integrated pharmaceutical production units and product engineering technologies, for sustainable pharmaceutical production, with the aim of reducing time-to-market and increasing product quality, therefore providing considerable increase in quality of life, for example, by making new pharmaceutical products available more quickly and at lower cost.
Proposed by: Dr Zoltan K Nagy Primary Supervisor
Secondary Supervisor: Dr Huaiyu Yang
Project ref: ZKNCG026
Covid-19 drug delivery using novel microneedles (urgent PhD Project)
The recent case of the Covid-19 pandemic has raised the question on which drug, if any, is to be delivered to patients with corona virus. As of March 2020, there is no specific drug that may be delivered for treatment of COVID-19 but a number of potential drugs have been suggested that may relieve the symptoms of Covid-19. The difficulty here is to how to deliver these drugs at a controlled manner over a long duration of time, particularly for elderly population who seem to be most affected, while also maintaining a physical distance from the patient. In addressing this point, the proposed work aims to develop a novel polymeric microneedle for target drug molecules.
Aim, Proposed Tasks and Methods:
The aim of this PhD project is to explore the following three main areas with a view to aid development of effective transdermal Covid-19 drug delivery system.
Aim I. Identification of Optimum Microneedle Design
The most effective geometry of microneedle arrays will be identified to increase the Covid-19 Drug permeability in skin, such as needle diameters, needle spacing, needle array pattern, penetration depth, and so on, for known biocompatible materials (e.g. silicon, PLGA, etc.). This step requires 3D model building for not only microneedle geometry and mechanical properties, but also Covid-19 Drug pharmacodynamics in skin and blood. These will be done by using finite element models which have been developed by Dr DB Das and his co-workers.
Aim II. Fabrication of Optimised Microneedles
Once a preliminary study on the optimised microneedle is conducted, a method to fabricate these systems will be developed for specific material.
Aim III. Optimisation of Covid-19 Drug Formulation for loading into Microneedle
This aim is relevant to the transport of biologically effective amounts of Covid-19 Drug into blood capillaries in different circumstances. A desirable Covid-19 Drug delivery system calls for very accurate dosing, complex release patterns, local delivery and biological stability. It has been shown that microneedles can be loaded/coated with a variety of drug formulations. In this task, attempts will be made to optimise Covid-19 Drug formulations and load them onto micro needle for this specific case, so that Covid-19 Drug can be released over an extended period of time, ranging from hours to days. This would facilitate development of the system for clinical studies as well as their applications in humans with more confidence.
Proposed by: Dr Diganta B Das
Project ref: DBDCG025
In-situ bioremediation and biomonitoring of non-aqueous phase liquids (NAPLs) - Dr Diganta B Das and Prof Paul Wood, Ref: DBDCG024
A large number of economically impoverished communities around the world face the daily challenges associated with contaminated drinking water. In particular, rural and remote communities in poor socio-economic conditions typically lack conventional water treatment, remediation or monitoring systems. Even where communities have access to low-cost remediation systems, existing pollution pressures and sources, such as those associated with non-aqueous phase liquids (NAPLs) (oil like contaminants) from industrial sites (ongoing or abandoned sites) may not be easily treated or degrade significantly by natural attenuation processes.
NAPLs compounds have been identified as important organic contaminants in surface and subsurface waters which may result in adverse ecological and human health effects over the long-term. An improved understanding of the level of NAPL contamination in the field, the bioremediation processes that control biodegradation of the NAPL contaminants and ways to bio-monitor them are required to effectively implement environmentally friendly technology for decontaminating polluted sites.
The primary objective of the proposed PhD research is therefore to develop a self-sustaining in-situ bioremediation and biomonitoring technique. This technique will be developed with direct consideration of the biogeochemical processes and interactions essential to the bioremediation process and transport of pollutants in the groundwater system under varying climatic conditions. The research will also aim to optimize the detection and to develop a bioremediation system for deployment within low income communities, which can then maximize the removal of NAPLs.
The research will consist of two work-packages (WP) occurring simultaneously:
WP1 - zero to multi-dimensional laboratory scale experiment and numerical modelling to investigate NAPLs biogeochemical interactions, fate and transport under varying (sub)-surface conditions,
WP2 - development of simultaneous bioremediation and biomonitoring techniques based on the results identified in WP1.
The project aims to extend concepts of bioremediation and biomonitoring developed via a previous EPSRC project, a recent EPSRC Institutional Fund and an ongoing UKIERI project. The proposed PhD project also fit very well with the UK’s strategic research agenda on global challenge such as funded by the GCRF scheme. In particular, the PhD project is an ODA (overseas development assistant) compliant research project, therefore, it will have the potential to bring economic benefits in many developing countries (e.g., China/India (petroleum oil refinery), Malaysia (palm oil contamination), Nigeria and Azerbizan (oil pipe line leaks and sabotage), by providing clean water and improved health. In the UK it is relevant for automobile oil pollution such as near road and parking places.
The developed remediation techniques will be key for field implementation at a site subject to surface and sub-surface NAPLs pollution. This study will help identify key parameters for field implementation and to what extent the prevailing environmental variability in parameters, including soil moisture content, availability of nutrients, temperature and groundwater flow affect the bioremediation and biomonitoring of NAPLs in both water and soil ecosystems.
Proposed by: Dr Diganta B Das Primary Supervisor
Secondary Supervisor: Prof Paul Wood
Project ref: DBDCG024
Decentralised water treatment system (DWTS) for provision of clean drinking water in humanitarian crisis settings - Dr Diganta B Das Prof Michael Henshaw, Ref: DBDCG023
Decentralised water treatment systems (DWTS) is not a ‘one size fits all’ technology; rather, it is a generic concept that defines water treatment using one or more stand-alone technologies.
The PhD project proposes to develop a resilient decentralised membrane-based water treatment system as a mobile technology.
Resilient water treatment system for humanitarian crisis setting needs to achieve operational flexibility to cope with rapidly changing and stressed environments. However, this must be achieved at a low cost for the viability of the DWTS. This PhD project will aim to develop a framework for architecting the integration of multiple physical systems (i.e. systems of systems) to support both the design of the DWTS and as a decision aid for deployment and reconfiguration during a dynamic humanitarian crisis situation (e.g. flood). A major challenge will be to identify effective architectural solutions across widely differing scales over which the membrane systems need to operate depending on unique the water treatment requirements and goals. To fully explore the DWTS design space, it will be necessary therefore to couple a number of systems models (not previously integrated as evidenced in the literature); these will be practically explored through consideration of different unit operations and membrane configurations. The aim will be to not only identify valid system architectures that satisfy the goal of treating water within the existing local constraints but also to identify undesirable emergent behaviour/properties of the system. Often the resilience of water treatment systems in the field is low, which makes it less effective over time. Also, the role of human interactions and movement/migration in the design of resilient water treatment systems is not well understood. This novel application of the systems approach will be addressed in this PhD project. The project will involve both theoretical and experimental work. The experimental work will involve the use of an existing membrane treatment facility in the department for validations of the developed framework.
The PhD student will also be expected to work with Institute of Artificial Intelligence, DMU, UK as a collaborator.
Proposed by: Dr Diganta B Das Primary Supervisor
Secondary Supervisor: Prof Michael Henshaw
Project ref: DBDCG023
High-throughput microfluidic screening of bacterial libraries and enzymes - Dr Goran Vladisavljević and Dr Guido Bolognesi Ref: GVCG022
A 3-year PhD project is available in the Department of Chemical Engineering of Loughborough University to work in collaboration with the University of Belgrade and Imperial College London on the development of microfluidic strategies for encapsulation of single bacterial cells within hydrogel particles for the purpose of their high-throughput screening.
Natural enzymes evolved over billions of years to allow for their nearly perfect catalytic activity in living organisms. Despite their wide structural diversity, relatively few natural enzymes have been successfully applied to industrial processes. The reason for this is that natural enzymes are adopted to work under physiological conditions, while industrial processes often require enzymes that are stable and active under harsh conditions. Directed evolution is the process by which biological entities such as cells and enzymes with improved properties are created over a short period of time (compared to natural evolution) by mimicking Darwinian evolution principles in the lab through iterative rounds of random mutagenesis and library screening. The conventional methods for enzyme screening are time consuming and often regarded as a bottleneck in directed evolution. Recently, droplet microfluidic methods have been developed for an efficient in-vitro compartmentalisation and fast evaluation of millions of enzyme variants in their bacterial hosts.
In this PhD project, novel microfluidic strategies for the encapsulation of single bacteria in monodispersed microdroplets will be developed, which is a crucial first step in the process of directed evolution. Generated droplets will be transformed into gel beads using various gelation strategies that will be developed in the project. After incubation, the cells will grow into monoclonal colonies inside the beads and can be sorted based on their fluorescence, isolated from the beads, and used for the next round of the process. Particle Microfluidics Group is well equipped with various devices for generation of monodispersed droplets.
The project will benefit from a direct access to a wide range of state-of-the-art materials characterisation facilities available in the Loughborough Materials Characterisation Centre. The hydrogel microparticles will be characterised using Confocal Laser Scanning Microscopy (CLSM), Focused Ion Beam Scanning Electron Microscopy (FIB-SEM), continuous online Fourier transform infrared (FT-IR) spectrometry and other characterisation techniques.
For more information on our research group, visit the group website www.particlemicrofluidics.com
Proposed by: Dr Goran Vladisavljević Primary Supervisor
Secondary Supervisor: Dr Guido Bolognesi
Project ref: GVCG022
Through the use of continuous, low-intensity, sub-cavitational acoustic fields, this project aims to transform processes across a wide range of industries where crystallisation is a key production, purification or separation stage including the substantial economic sectors of pharma, food and polymer processing. The project will also address processes where there is the potential to enhance mass-transfer through the use of acoustic fields, for example bubble column reactors. Although high-intensity acoustic fields have been adopted in sono-chemistry and sono-crystallisation, the use of fields at much lower energy levels has recently been patented as a method of crystal nucleation control. However, the mechanisms for the effects that have been observed experimentally are very poorly understood, and much work is required to build understanding of the phenomena of heat and mass transfer that drive the effect in order to ensure the technology can deliver the impact that it has the potential to achieve. It is believed that similar mass transfer processes may also be enhanced by low intensity acoustic fields in processes involving bubbles and this has yet to be explored.
The project will involve the implementation of acoustic nucleation into continuous crystallisation processes, and the use of parametrised models and advanced control techniques to deliver control of crystal size distribution and polymorph.
The project addresses the EPSRC priority theme of Manufacturing the Future by developing enhanced process techniques with smart control mechanisms and by reducing energy usage for advanced processes. An EPSRC proposal is close to being submitted (led by Leeds university, together with our research group at Loughborough, an SME and Diamond Light Source) on the acoustic-enhanced crystallisation process and, if that project is funded, this PhD programme would work alongside that it, with a team of academics and 3 postdoctoral researchers.
Bio-oil upgrading by zeolite-supported transition metal carbide, nitride and phosphide catalysts - Dr Johnathan Wagner, Ref: JWCG002
The past two decades have seen considerable research into the development of thermochemical processes (e.g. pyrolysis, hydrothermal liquefaction) to convert a wide range of low-quality biomass feedstocks (e.g. agricultural residues, woods, grasses, microalgae) into crude biooils, which can be further upgraded into sustainable, liquid biofuels. One of the main barriers to the commercialisation of these technologies is the high cost of bio-oil upgrading, required to eliminate high concentrations of oxygen and nitrogen and improve the bio-oil physical properties (LCICG, 2012). Most existing bio-oil upgrading research has been limited to sulphided transition metal catalysts or noble metal catalysts, neither of which appear commercially feasible, due to the requirement to co-feed sulphur (sulphides) or their high cost (noble metals). Over the last 5-10 years, transition metal carbides, nitrides and phosphides have emerged as potentially stable, low-cost alternatives (Ruddy, 2014), but further work is required to combine these with high-surface area, acidic supports to yield bifunctional upgrading catalysts. Particularly the strong interaction of phosphorus with aluminium during the synthesis of zeolite-supported phosphides remains a challenge, resulting in undesired support modifications (Wagner, 2018).
Project: The aim of this project is to develop improved catalytic processes for bio-oil upgrading, based on transition-metal carbide, nitride and phosphide catalysts. These catalysts will be combined with high-surface area, acidic supports (e.g. zeolites) to produce stable and low-cost bifunctional catalysts. Different methods of catalyst loading and converting the metal oxide precursors into the active carbide, nitride and phosphide configurations will be explored to maximise the synergy between the active metals and the support. Materials will be characterized through physical, chemical and spectroscopic techniques (e.g. XRD, EDX, BET, TPR) to confirm active phase formation and retention of support properties. Catalytic testing will be conducted initially using model compounds to correlate reaction mechanisms to the catalyst material properties. Based on this, most active catalyst systems will be selected and applied to the upgrading of thermochemically produced bio-oils.
Proposed by: Dr Johnathan Wagner
Spray drying is an important industrial process for the manufacture of a wide variety of products in the pharmaceutical, food and chemicals industries, amongst others. The energy efficiency and the form of the final particles is heavily dependent on the kinetics of droplet drying. This is a complex transition from a liquid droplet to a solid particle and is still not fully understood. The main difficulty is that studying droplets in sprays is inherently very complex. They are very large in number, have a wide range of sizes, are contacting gas with variable humidity and temperatures within the same chamber, and are all moving very quickly at different velocities. Currently, the only good data on droplet drying come from studying single droplets, but this suffers from the disadvantage that the studied droplets are much larger in size (1 mm instead of 5-200 microns in spray drying) and are usually in a static environment.
The project will use a piezoelectric atomiser to produce droplet streams where all droplets have the same size (which are in the spray drying range), and these will be introduced into a tall (6 m) but narrow (10 cm) column which will uniquely enable the droplets to be imaged at different points in the drying process. Size information extracted from the images will enable agglomeration and drying to be studied and fitted to models. This will open the door to improved models that will enable drying to be optimised in terms of energy efficiency and product quality in a multitude of applications.
Proposed by: Dr Andy Stapley
A Systems-Level Investigation of Cancer Cell Metabolism for Developing Novel and Targeted Chemotherapies - Dr Ahsan Islam and Dr Mhairi Morris, Ref: AICG004
Cancer is a generalized term for an intricate collection of many diseases demonstrated by uncontrolled division and spread of abnormal cells in the human body. Thus, cancer originates in cells, the building blocks of a human body. Since cancer is primarily caused by genetic mutations in cells, research in cancer genomics is widespread. Genetic studies, however, cannot provide information on cellular metabolic activities, simply because the former is, in principle, qualitative while the latter is quantitative. The pathway level quantitative details will be instrumental in cancer research as such mechanistic information can eventually lead to better drug target and drug discovery for cancer cells. Moreover, the mechanistic understanding of intracellular metabolic reprogramming in cancer cells provides a promising avenue for developing improved, effective, and targeted chemotherapy drugs realising the potential of personalised medicine. The advent of cutting-edge metabolic engineering tools such as 13C-MFA (Metabolic Flux Analysis) now allows us to deduce the fluxes i.e., the rates of intracellular biochemical reactions at the systems-level. The 13C-MFA essentially employs a detailed, systems-level mathematical model of cellular metabolism, along with metabolomics data generated from stable isotope such as 13C (carbon 13)-labelled substrate-fed growth experiments of cancer cells.
This project will, thus, focus on generating GC-MS and LC-MS data for both normal and cancer cells growing on 13C-labelled substrates (e.g., glucose, glutamine). The intracellular fluxes will then be estimated from the generated data using a systems-level mathematical model of cellular metabolism. These fluxes will provide a clear landscape of cellular metabolic activities and metabolic alterations in normal and cancer cells, ultimately guiding us to develop novel and targeted chemotherapies. Moreover, such an integrated system will be instrumental not only for novel drug discovery, but also for analysing and understanding the mechanism of existing chemotherapy drugs. Such mechanistic underpinning can eventually lead to the treatment of a range of cancers by the drugs that are currently being used for treating only a specific type of cancer. Specific milestones of the project include: (a) developing a generalised systems-wide mathematical model of metabolism of cancer cells, and (b) integrating metabolomics and isotope labelling data from 13C-labelled experiments to estimate the intracellular metabolic fluxes in normal and cancer cells.
Proposed by: Dr Ahsan Islam and Dr Mhairi Morris (School of Sport, Exercise and Health Sciences)
Metabolic Engineering of ANAMMOX Bacteria for Mitigating Nitrogen Pollution and Balancing the Nitrogen (N)-Cycle - Dr Ahsan Islam and Dr
Diganta Das, Ref: AICG005
Although global carbon footprint and its effects on the carbon cycle have attracted widespread attention from scientific communities and general public alike, nitrogen (N)-cycle is the one that altered the most and suffered irrevocable damage due to uncontrolled human activities — so much so that managing the N-cycle has been described as one of the grand engineering challenges of the 21st century by the US National Academy of Engineering. Despite being abundant in atmosphere, nitrogen is not readily available to living systems due to its inert nature. Living systems, in which nitrogen is the backbone of DNA and amino acids, obtain this vital element from food where atmospheric nitrogen is fixed as nutrients by plants. Subsequently, the cycle is closed by the return (i.e., denitrification) of fixed nitrogen compounds to atmosphere as dinitrogen through microbial activities. However, uncontrolled human activities such as excessive nitrogen removal from atmosphere for the production nitrogen-rich fertilizers disrupted the natural N-cycle because the industrial nitrogen fixation activities exceed far more than dinitrogen return to atmosphere by microbial denitrification processes. Moreover, the fixed nitrogen compounds (i.e., ammonium, nitrate and nitrite) when accumulate in abundance in the environment due to synthetic fertilizer runoff from agricultural farmlands cause nitrogen pollution to fuel algal bloom, generate red tides and dead zones in oceans. Thus, increasing microbial denitrification processes will be a sustainable solution to not only managing the N-cycle but also mitigating nitrogen pollution as reducing fertilizer production will negatively impact world food supply.
Anaerobic ammonium oxidizing (Anammox) bacteria use fixed nitrogen compounds as substrates to produce inert dinitrogen gas that can solve both issues. However, slow growth of these bacteria is a major impediment for scaling up and industrial implementation of the Anammox process. This project aims to develop a detailed mathematical model of Anammox bacteria metabolism using bioinformatics and systems biology tools, so that strategies for accelerating their growth rates can be identified. These strategies will then be implemented experimentally using anaerobic microbiology and molecular biology tools for metabolic engineering of Anammox bacteria to develop efficient microbial cell factories to mitigate nitrogen pollution, as well as to balance the N-cycle.
Microfabrication and manipulation of functional lipid-based particles for bio-analytical microdevices - Dr Guido Bolognesi and Dr Goran Vladisavljevic, Ref: GBCG006
This project aims to design, manufacture and characterise lipid-based nano- and micro-particles to be used as smart biosensors in novel microfluidic devices for bio-analytical and healthcare applications. Lipid-based particles are ubiquitous in a broad range of industrial applications, including drug delivery, medical diagnostics/therapeutics, pharmaceutics and food. In this context,
microfluidics has proven to be a valuable tool for the synthesis, manipulation and characterisation of those particles, including stimuli-responsive liposomes, lipid-coated solid and hydrogel particles. The combination of particle-based and microfluidic technologies can hence lead to a new generation of bio-analytical and diagnostic microdevices with the potential to overcome many limitations of traditional laboratory technologies.
The objectives of this project are i) to engineer bespoke bio-sensing particles by means of droplet-based microfluidics technologies, ii) to develop proof-of-principle bio-analytical microfluidic devices for the rapid and ultrasensitive detection of target analytes based on the micromanipulation of the bio-sensing particles. The successful candidate will design and fabricate microfluidic systems by photo-/soft-lithography procedures and 3D printing techniques. He/she will microfluidically generate bespoke particles and characterise their properties and functionalities by a wide number of experimental techniques, including optical and electron microscopy, fluorescence spectroscopy, DSC, ATR-FTIR and XRD. He/she will also undertake proof-of-concept studies to identify prospective applications of the developed microfluidic devices - especially for drug delivery and point-of-care diagnostics.
This PhD project is aligned with the EPSRC research grant “FAST for bio-analysis in microfluidic devices” and a successful candidate would be expected to engage in collaborations with the internal and external members of the research team.
Microfluidic production of drug-loaded biodegradable polymer microparticles for coating cardiovascular catheters - Dr Goran Vladisavljevic and Dr Guido Bolognesi, Ref: GVCG007
This project would work in collaboration with two industrial partners (a Switzerland based medical device supplier and a leading UK manufacturer of microfluidic devices) on the development of drug-loaded microparticles for coating implantable medical devices.
In this PhD project, a novel state-of-the-art microfluidic platform with custom-made microfluidic chips will be used to produce drug-encapsulated biodegradable polymer microparticles for coating medical devices to prevent restenosis. The use of microfluidic devices for production of microparticles for pharmaceutical applications enables superior control over particle size and high encapsulation efficiency of entrapped drugs. Precise particle production is crucial to achieve a predictable biodegradation of polymers such as PLGA and controlled drug release. It is possible to tune the release profiles from the polymer-drug matrix by controlling polymer molecular weight, ratio of lactide to glycolide, drug concentration, particle size and release medium. In addition, drug distribution within the polymer matrix can be tuned by controlling the rate of solvent evaporation and drug-polymer compatibility, which can lead to different degrees of drug-polymer phase separation.
The microparticles will be characterised using Confocal Laser Scanning Microscopy (CLSM), Focused Ion Beam Scanning Electron Microscopy (FIB-SEM), X-Ray Diffraction (XRD), and other characterisation techniques. The encapsulation efficiency and release behaviour of encapsulated immunosuppressive drugs will be investigated using HPLC and UV–vis spectroscopy. The properties of dispersion medium will be adjusted to allow optimum drug release kinetics for in-vitro studies.
The project will benefit from a direct access to a wide range of state-of-the-art materials characterisation facilities available in the Loughborough Materials Characterisation Centre. The project is aligned with a project funded by the National Productivity Investment Fund and the successful candidate is expected to collaborate with the research team and external collaborators working on this project.
The interaction between oil and foam has been the subject of investigation for many years: originally oil was studied as an efficient defoaming agent required in various industrial applications where undesired foaming may occur (for example, waste water treatment plant). However, oil and foam can also co-exist as happens in detergency, fire-fighting, food and petroleum industries, where oil can be in the foam structure or put into contact with the foam without observing a break-up of the foam. Under specific physico-chemical conditions, the oil phase can be trapped inside the aqueous network of the foam, without breaking the foam. The latter is of considerable importance in the case of cleaning of oily surfaces using cleaning liquids and using shampoo on oily hair. The most important application is oil recovery and purification of produced water.
The project will include investigations of:
- Stability of thin non-symmetric layer between water/air and water/oil interfaces under no-equilibrium conditions. Both interfaces are mobile. Theory and experimental investigations.
- Experimental investigations of foam stability in the presence of oil and connection between mobility of interfaces and stability of foams using theoretical predictions from part 1. Instead of air oil with air will be supplied to make a foam with oil inside.
- Computer simulation of oil droplet motion inside Plateau border and interaction with air/liquid interfaces. Computer simulations and experiments to verify the theory predictions. It is necessary to select a proper formulation to have foams stable. In this part foam will be created and on the top of the foam an pure oil or unstable oil in water emulsion.
The sales of biopharmaceuticals and biotherapy from only Humira, Remicade, and Enbrel are over $18 billion in US in 2015. Protein therapy is expected to make about $250 billion in savings for US over the next 10 years. Manufacturing biopharmaceuticals in a cost effective and reliable route becomes a major challenge for meeting the rapidly growing demands of protein-based medicines. Crystallisation of proteins (like insulin) as one-step operation is more efficient, leading to advantages of stability storage, formulation and drug delivery.
This PhD project aims to develop innovative methods on (bio)crystalisation of (bio)pharmaceuticals, including macromolecules (proteins, virus, and etc) and small molecules. The protein crystallisation has started to be applied in industrial for increasing the efficiency and decrease the cost of manufacturing. The project will focus on protein or small organic molecular crystallisation with thin film solution to accelerate crystallisation and purification of proteins. Nano-templates with different materials may also be used to enhance the nucleation of the protein to further improve the efficiency. The project is interdisciplinary, and this will provide PhD student a good opportunity to be trained to face the challenge of the future (bio)pharmaceutical manufacturing. The successful project will lead to a revolution in application of crystallisation with thin film solution in manufacturing of biopharmaceuticals.
The ideal student would have an interest in the (bio)pharmaceutical crystallisation, biomanufacturing, biotechnology and bioseperation, and possess strong chemical engineering or biotechnology skills.
Proposed by: Dr Huaiyu Yang
Electrokinetic flows in foams - Dr Hemaka Bandulasena, Dr Anna Trybala, Prof Victor Starov, Ref: HBCG010
Investigating electrokinetic transport in a liquid foam is at the intersections of two well developed research areas (1) the study of electrokinetic flows (i.e. surface-driven flows generated close to a charged interface) is well understood and documented in regards to the solid/liquid interfaces; (2) the flow of liquid in a 3D deformable network, i.e a foam drainage, under a combined action of capillary forces and gravity has been under investigation for a long time . The overlapping zone of these two area is of great interest for both communities as it gives rise to challenging new problems (i) the importance of the nature of the charged interface, created by mobile and soluble surfactants in the case of foam, on electrokinetic transport; (ii) foam behaviour submitted to a surface-driven flow; (iii) compensation of a volume-driven flow, i.e. /capillary/gravity, by a surface-driven flow, i.e. electroosmosis. Electrokinetic phenomena in liquids and porous materials is well developed area since the 19th century. However, the corresponding phenomena in foams only started to be developed since the end of 20th century. Equations, which describe foam drainage under the action of both capillary and gravity forces were developed and widely used. However, the deduced equation includes only Plateau borders between bubbles but does not include flow inside the thin films. However, in the case of a flow caused by an imposed electric field the flow inside thin film is becoming important and has to be considered.
The aims of this project are:
- modification of a theory of foam drainage to include a flow caused not only by capillary and gravity action but also by applied electric field,
- computer simulations according to the deduced equation,
- experimental investigations of flow caused by applied electric filed and comparison with the theoretical predictions,
- experimental investigation of the foam drainage in the presence of applied electric field and comparison against the developed theory predictions.
Protein therapy is expected to create ~$250 billion in savings over the next 10 years. Despite the increasing success in discovering protein-based medicines, manufacturing at scale remains a significant challenge. The cells produce therapeutic protein and store them inside the cell.
This project is focused on cell culture and cell line development of therapeutic proteins, such as insulin and mAbs, and regeneratively manufacturing protein inside cell. By understanding the mechanism of producing circle inside the cell, the project is targeted to improve the biomanufacturing and solve the challenges of biopharmaceutical industrial. This PhD research project will be aligned with an EPSRC funded project.
Microfluidic biocrystallisation with micro bubbles templates - Dr Huaiyu Yang and Dr Hemaka Bandulasena, Ref: HYCG012
Over the past three decades, protein-based biological products (i.e. biologics) have been an important channel of innovation in the pharmaceutical industry. Between 1993 - 2015, a total of 107 biologics have been approved, accounting for a global market value of $175 billion. However, manufacturing the biopharmaceutical is still a significant challenge for biopharmaceutical industrials, due to the complex and costly purification technology used.
The purpose of this novel research project on microbubble-assisted biocrystallisation is to develop an efficient and low-cost technology to purify biopharmaceuticals, especially proteins. We envisage that this technology could be widely applied to improve the manufacturing of pharmaceuticals, such as insulin and monoclonal antibodies (mAbs). Precise control required for the separation process is achieved using a highly controlled microfluidic device. Microbubbles generated by fluidic oscillation or cavitation will provide a template for crystallization and facilitate final product separation. Numerical Simulations might be performed to identify optimum operating conditions for separation and to understand key mechanisms at play. By combing biocrystallisation and microfluidic technology, it is excepted to help to solve the challenges in biopharmaceutical manufacturing.
Sustainable Production of Biodegradable Microcapsules by Membrane Emulsification - Dr Marijana Dragosavac and Dr Hemaka Bandulasena, Ref: MDCG013
Encapsulated microparticles are critical in the development of emerging science and technology. EPSRC recognises the importance of developing innovative manufacturing processes and has envisaged that a fundamental approach toward complex fluids and encapsulated microparticles has the potential to revolutionise manufacturing of high value products including personalised medicine and novel functional food.
Encapsulation is a key enabling technology for improvements in human health and well-being. A range of encapsulation techniques are available or under development for production of microcapsules from the nm to mm scales. However, much more progress in fundamental research and innovation is required to overcome the challenges for encapsulation in the food and health domain, in particular on how the disruptive technology of membrane emulsification often opens up opportunities for re-formulation using materials that are environmentally more sustainable.
The objective of this PhD project, in collaboration with Croda, is to investigate the encapsulation of materials relevant to Croda’s formulations. Encapsulation via entrapment within ionic or thermal gelling polymer systems, or via microencapsulation within semi-permeable membranes, both require the use of an emulsification step followed by an additional batch treatment to form gelled microspheres or membrane-coated microcapsules containing water and/or oil soluble encapsulants.
In conventional processing formulated particles are often in the millimetre size range. However, to improve the mass transfer characteristics and process efficiency, encapsulation within smaller droplets is needed in combination with a continuous solidification step.
To fulfil this aim, a novel technique - membrane emulsification coupled with reaction to produce the drops containing both water and oil soluble encapsulants will be used in combination with an oscillating reactor for solidification step. Membrane emulsification is a technique that uses a low pressure to force the dispersed phase (containing encapsulants) to permeate through a membrane into another immiscible liquid. A gentle shear is generated above the membrane that detaches the droplets from the membrane surface. The technique is highly attractive given its simplicity, potentially lower energy demands, need for less surfactant and the resulting narrow droplet size distribution. Using the same membrane, but varying the shear on the membrane surface, results in droplets of different size being produced. The process can be scaled up by providing a larger membrane area.
The student will investigate the influence of the rheology of the various sustainable biopolymer/oil systems, encapsulants (chosen by Croda and to be well characterised as part of the project) concentrations, interfacial phenomena, membrane pore size, as well as operating conditions (dispersed phase flowrate and shear stress) on the droplet size forming on the stainless-steel membrane reactor. Stability of the shells to keep the encapsulants will be investigated in order to understand how to optimise the shelf life of the product. Understanding the effects on performance in a range of formulation applications will be examined with the intention to obtain a free-flowing powder.
Integrated modular microfluidic platform for screening and production of personalised pharmaceuticals - Dr Brahim Benyahia, Ref: BBCG014
The pharmaceutical and biopharmaceutical industries are undergoing a paradigm shift with the development and adoption of more flexible regulatory tools such as Quality-by-Design (QbD), agile lean and cost-effective manufacturing technologies and robust decision-making and screening strategies. Continuous manufacturing (CM) spearheads this unpresented innovation and is gradually gaining ground. CM presents multiple potential benefits for the pharmaceutical and biopharmaceutical sectors, particularly enhanced flexibility and quality, lower production and cleaning costs, higher equipment utilization rates, smaller facility footprints and shorter time to the market. However, the emergence of continuous pharmaceutical technologies is hampered by various technical challenges despite the significant strides forward over the last few years. There is still an increasing need for cost-effective continuous technologies, precision medicine, modular small-scale platforms for personalised drugs (e.g. orphan or rare diseases drugs) and flexible manufacturing technologies for clinical trials and post-clinical validation.
This PhD project is a great opportunity to develop a novel integrated modular microfluidic platform for pharma on demand: just in time production of personalised drugs with fine tuneable critical quality attributes (e.g. efficacy, dissolution). We have already achieved well controlled crystallisation in a new microfluidic platform that was recently designed, validated and patented. This PhD project will investigate the integration of further downstream processing technologies and the development of a modular microfluidic platform to produce small quantities of bespoke or personalised drugs under rigorous QbD considerations. Novel 3D printing technologies will be used in this project alongside conventional microfluidic technologies. The project will also investigate the integration of real time process analytical technologies to monitor and control the operating conditions.
Proposed by: Dr Brahim Benyahia
Developing next generation alkaline direct fuel cells using liquid bio-fuels for transport and high-performance electronic devices - Prof. Wen-Feng Lin, Prof. Rui Chen and Dr Ashley Fly, Ref: WFLCG015
With environmental concerns and depleting fossil fuels, there is an increasing demand for alternate means for production of clean energy, and fuel cells can play an important part in the efficient utilisation of chemical energy to produce clean electrical energy.
The overall aims of this project are to draw together the nascent work on new catalysts and supports for the anode and cathode, the anion exchange membrane (AEM), membrane-electrode-assembly, and fuel cell system development to determine the feasibility of formulating low cost and high performance (active and durable) membrane electrode assemblies for alkaline direct liquid-feed fuel cells, accessing a wider range of high energy liquid fuels – particularly biofuels such as bio-ethanol and bio-butanol. A key aspect of the catalyst research will be fundamental understanding of both the anode and cathode reaction processes at atomic and molecular level in order to formulate a theoretical model to aid in the identification of catalyst breakthroughs for efficient (bio)fuel oxidation and oxygen reduction reactions in alkaline media.
Part of the project has been supported by the Royal Society and the Newton Fund, and the National Natural Science Foundation of China, with a long-term collaboration with Prof Sun at Beijing University of Chemical Technology, the PhD student will have opportunities to visit BUCT for collaboration.
Wound smell-printing; diagnostic bioprofiling of chronic wounds to tackle antimicrobial resistance - Dr Elizabeth Ratcliffe, Dr Martin Lindley, Dr Matt Turner, Dr Eugenie Hunsicker, Ref: ERCG016
Overview: A multi-disciplinary PhD project is considered to develop a new rapid diagnostic test for use at the point-of-care for wound infections by using sensors that can detect smell-print profiles for different types of wound infection, based on compounds released from microbes within the wound, to identify problem organisms and serious infections.
The PhD is led by Loughborough’s Chemical Engineering Centre for Biological Engineering and supported by a supervisory team from Sports Exercise and Health Sciences, Chemistry and Maths departments with links to a collaborative research platform in Translational Chemical Biology and industry (Advion Ltd).
Challenges: Current wound infection diagnosis relies on wound surface swabs and microbial culture, the process takes more than 48 hours to return a result and has poor sensitivity and specificity, contributing to delayed accurate treatment and non-target antibiotic use. Development of more accurate and informative rapid diagnostic tests will enable earlier and more targeted intervention to mitigate risks of serious wound infections, improve patient outcomes (through complication avoidance) and lower treatment costs. Wound infections are a staggering challenge in the National Health Service (NHS) with more than 2.2 million wounds being managed annually and 15% remaining unresolved after 1 year. Managing these wounds includes 29.5 million practice and community nurse visits, 7.7 million GP visits and 3.4 million hospital outpatient visits, at an estimated cost of approximately £5 billion. Antibiotic resistance rates are increasing at an alarming rate with 10 million annual deaths and $100 trillion global economy costs predicted by 2050. Rising rates of diabetes, obesity and an ageing population means chronic wound infections are a staggeringly increasing challenge. New antibiotic development is at an all-time low, it is therefore of extreme importance to accelerate the development of new technologies to conserve current options, ensuring optimal use and provide more effective future options.
PhD Aims: To develop a new rapid point-of-care diagnostic test for wound infections using sensors that can detect volatile organic compounds (VOCs) released from microbes and the wound niche to identify bio-profiles for problem organisms and biofilm phenotype. Initially, the project will seek to develop discriminative analysis of VOC bio-profiles to enable triaging of biomarker compounds and creation of a profile library for wound and diabetic foot ulcer bacterial isolates under a matrix of in-vitro culture conditions (e.g. agars, broth, wound fluids, time-course biofilm assays), to detect antimicrobial resistant organisms (e.g. EMRSA-15, EMRSA-16) and onset of biofilm phenotype (e.g. MSCRAMM, poly-N-acetylglucosamine expression). The project will explore development of a clinical reference library of isolate profiles and infection model data for pattern recognition and distinction to measure accuracy and sensitivity of simulated diagnosis.
Proposed by: Dr Elizabeth Ratcliffe, Dr Martin Lindley, Dr Matt Turner, Dr Eugenie Hunsicker
Viral Bioprocessing Toolkit; new process analytical techniques for advanced therapeutics manufactured from viruses - Dr Elizabeth Ratcliffe, Dr Martin Lindley, Dr Jim Reynolds, Dr Liam Heaney, Ref: ERCG017
Overview: A multi-disciplinary PhD project is being considered to develop new process analytical techniques for standardised manufacture of advanced therapeutics from viral production processes such as viral gene therapies and bacteriophage treatments by using sensors that can detect viral burst from host production cells during the infection process for manufacture.
The PhD is led by Loughborough’s Chemical Engineering Centre for Biological Engineering and supported by a supervisory team from Sports Exercise and Health Sciences and Chemistry departments with links to a collaborative research platform in Translational Chemical Biology and industry (Advion Ltd).
Challenges: Although clinical studies clearly indicate that viral based therapies such as gene therapies and bacteriophage therapies are fast becoming a part of future molecular medicine practise, they also reveal numerous difficulties and limitations that require attention. Key challenges across the sector include bottlenecks in manufacture such as achieving the required numbers of cells and virus to realise the potential of these revolutionary treatments for all the patients that could benefit, as well as gaps in process analytical techniques to achieve the required level of characterisation of manufacturing processes and products for cost-effective manufacture. Therefore alternative tools and technologies are required to meet future clinical demand with Good Manufacturing Practises.
PhD Aims: The supervisors have investigated a range of analytical techniques for viral production processes and proof-of-concept data has shown that several techniques based on DNA, protein, and compounds released from cells may be linked to levels of virus production. The project will seek to develop these techniques further to establish quantifiable links between viral numbers from host production cells for accurate and sensitive process analysis.
Proposed by: Dr Elizabeth Ratcliffe, Dr Martin Lindley, Dr Jim Reynolds, Dr Liam Heaney
Despite the very many designs available on the market, two main features of rotor-stators are the small gap between the teeth or small holes on their screens and the high rotational speeds they are operated at. These result in high levels of energy dissipation in the vicinity of the rotor-stator head which makes them the equipment of choice for applications that require breakup. They are typically used for liquid-liquid dispersions/ emulsification and deagglomeration processes as well as other multiphase systems for example pickering emulsions. The rapidly rising uptake of nanotechnology with new products of superior properties being introduced to market also make them relevant to the manufacturing processes of new formulations with nanomaterials: dispersion of nanoparticles or delamination of layered structures such as nanoclays or graphite.
The design of processes that make use of rotor-stators can to a great extent rely on a trial and error type of approach due to limitations in the knowledge relating to process performance and scale up, resulting in the market introduction of novel products being delayed or hindered. To address these, a series of PhD projects is proposed which will study the following:
- Flow and power characteristics of different rotor-stator design using both experimental techniques and numerical modelling.
- Deagglomeration of fine powders in a liquid medium. This will include nanoparticles, nanoclays or graphite and will study the deagglomeration or delamination processes in relation to the flow field. Different formulations or partial formulations will include different particle-liquid pairs and concentrations.
- Breakup in liquid-liquid dispersions. This will involve different formulations with both different liquid-liquid pairs and also in three-phase systems. The breakage will be investigated in relation to the flow field.
All projects will make use of advanced analytical and numerical techniques to study the flow field, size the dispersions, or study the delamination process, characterise the flow behaviour/rheology of the dispersions also making use of process devices which are industrially relevant which will equip the PhD student with skills relevant to a wide range of applications in academia and industry.
Proposed by: Dr Nerime Gül Özcan-Taşkın
Large scale low-cost sustainable hydrogen production from seawater and renewable energy Prof. Wen-Feng Lin and Dr Jin Xuan, Ref: WFLCG019
Hydrogen is considered one of the most promising clean energy carriers, thanks to its high gravimetric energy density and environmentally friendly use. It is a clean and desirable way to produce pure hydrogen at the cathode via electrolysis of water driven by renewable energy, however, the water splitting is highly dependent on having an efficient and stable oxygen evolution reaction (OER) at the anode, to counterbalance the hydrogen evolution reaction (HER) at the cathode. Furthermore, water distribution issues may arise if vast amounts of purified water are used for hydrogen fuel production. On the other hand, seawater is the most abundant aqueous electrolyte feedstock on Earth but its implementation in the water-splitting process presents many challenges, especially for the anodic reaction. The most serious challenges in seawater splitting are posed by the chloride anions. Although under acidic conditions, the OER equilibrium potential is only slightly higher than that of chlorine evolution, under alkaline conditions, the equilibrium potential of OER is significantly shifted to lower value but that of chorine evolution does not change so much, which facilitates OER over chorine evolution with 0.490 V difference in potential domain.
Therefore, this project aims to develop highly efficient OER catalysts with an overpotential less than 0.480 V under alkaline conditions, together with highly efficient and low cost HER catalysts such as transitional metal carbides and nitrogen doped carbon nanomaterials. Then the prototype electrolyser will be assembled employing the catalysts so developed to demonstrate the catalyst performance at cell level.
Solar Fuel: Next generation hydrogen production from sunlight & renewables - Dr Jin Xuan, Ref: JXCG020
Renewable hydrogen will play an important role in our energy future for low carbon transport, heating, grid-scale energy storage and CO2 capture/utilisation. The UK's hydrogen demand would reach 143~860 TWh/year by 2050, while the current production capacity is only 27 TWh/year. Conversion of abundant sunlight to produce H2 is one of attractive approach to meet the demand. Among various solar H2 technology, photoelectrochemical (PEC) water splitting has gained much attention due to its operational flexibility, reduced electron-hole recombination and natural separation of H2 and O2 in two electrodes.
This PhD project aims at device innovation to build novel microfluidic PEC cells for eco-attractive production of solar hydrogen from photoelectrochemical water splitting. More specifically, the project objectives are (1) High solar-to-fuel efficiency with novel cell design to match electrochemical equilibrium potential with semiconductor band position. (2) Fast kinetics and stable performance underpinned by optimised microfluidics platform, and (3) Cost reduction by enabling the use of new types of PEC materials. The outcomes will contribute to achieving the UK's ambitious and legislated targets of 100 % renewable energy and 80 % carbon emission reduction by 2050. The platform developed in this project are critical to meet the UK energy and environmental demands, as well as ensuring security of supply.
Proposed by: Dr Jin Xuan
Depletion of fossil fuels and global warming have led to intense research on renewable energy sources that are sustainable and competitive. Biofuels produced from lignocellulose (i.e. non-food sources), termed second generation biofuels offer a promising solution to these problems if costs can be reduced. As the demand for food is increasing with rising population and with the limited availability of arable land, the use of starch derived from such crops (“first generation” biofuels) for fuel is considered not sustainable. 2nd generation biofuels are currently more expensive to produce than 1st generation. In order to produce biofuels economically from feedstocks such as food residues, non-edible crops and lignocellulosic residues such as e.g. corn stover, forestry residue, municipal solid waste and notably switchgrass; breakthroughs in technology related to key processes are essential.
In this PhD project, we aim to develop biofuel production from lignocellulosic materials, mainly focused on pretreatment and fermentation. The first stage involves pretreatment of lignocellulosic biomass using a novel microbubble-plasma reactor developed at Loughborough University. Various lignocellulosic feedstocks will be tested and the products from pretreatment will be analysed by enzymatic saccharification and chemical hydrolysis to determine the efficiency of carbohydrate release. Following the pretreatment step, continuous extraction capabilities of microbubbles in a fermentation reactor will be studied to improve cellulosic biofuel production. It is expected that continuous operation at higher substrate concentrations will dramatically improve the economics of production of cellulosic ethanol. Numerical Simulations will be carried out to help optimise the process and scaling up the units. This PhD project will be based in the Department of Chemical Engineering at Loughborough University.
Proposed by: Dr Hemaka Bandulasena
If you don't see a topic in the list of indicative projects that matches your requirements then more information on a the wider range of our research can be found by viewing our individual research areas:
- Pharmaceutical and Bioengineering
- Nano- and Micro- Scale Engineering
- Energy and Environmental Engineering
- Catalytic, Separation and Purification Technology
If you would like an informal conversation about any of the research areas or projects, you can either contact the named academic directly, or Dr Hemaka Bandulasena.