Image-based predictive modelling frameworks for personalised drug delivery in cancer therapy

Peer reviewe

Modelling of reverse osmosis membrane process and transport phenomena: from feed spacer to large-scale plants

The world’s water shortage problem has drawn immense attention and many researchers have tried to solve the problem by introducing water purification and seawater desalination. It is widely accepted that a reverse osmosis (RO) process is more effective in terms of separation capability and its simple installation and requires less energy than any other water purification and seawater desalination processes. However, its specific energy consumption is still higher than the theoretical minimum energy and there is scope for further improvement. Spiral wound modules are the most commonly used in large RO desalination plants, in which flat sheet membranes and spacers are alternately arranged and wrapped around a centre pipe. Feed spacers play an important role by keeping membrane sheets separate and enhancing mixing near membrane surfaces. This thesis focusses on identifying opportunities for enhancement of membrane performance, reductions in energy consumption and other costs via predictive modelling and model-based scenario studies. Firstly, a new mathematical model for a spiral wound module is developed by accounting for its unique geometric features. The performance of the spiral model is compared with existing models based on the plate-and-frame approach. The spiral model is then used to investigate the effects of geometric parameters on module performance and energy consumption, and further extended to simulate a large-scale RO process with multiple modules. Secondly, computational fluid dynamics (CFD) models for spacer-filled feed channels are built using two-dimensional geometric representations and simulated under a wide range of operating and geometric conditions. A new boundary condition is introduced in the CFD models by reformulating the solution-diffusion model in order to describe permeable membrane walls. As a result, the effects of different operating and geometric conditions in the presence of spacers can be assessed in terms of key performance indicators such as water flux, concentration polarisation modulus and pressure drop. A large number of numerical simulations have been carried out and the results are used to derive empirical correlations for concentration polarisation and pressure loss in a feed channel, in order to facilitate the incorporation of the impact of spacers in a process model. The new correlations are implemented in a process model and compared with existing correlations that were experimentally derived in terms of predicted performance and energy consumption. Finally, three-dimensional CFD models for various spacer designs are developed by varying filament configuration, mesh angle and flow attack angle. By implementing the proposed boundary condition for permeable membrane walls, the CFD models presented here can be utilised to predict membrane performance for a given feed spacer type and geometry.Open Acces

Simulation Model for Prediction of Gas Separation in Membrane Contactor Process

The purpose of this study is to establish a practical simulation model based on mass balance, mass transport equations and equilibrium equation between gas and liquid phases across a porous membrane in membrane contactor process in order to predict the separation behavior by the gassing process of gas mixture in membrane contactor. The established simulation model was verified by comparison between the simulated values and real process values in the separation of CH4/CO2 mixture, showing an excellent agreement between them. The parameter R-value in the model, which is a kind of the permeability of permeant across porous membrane, has been determined by fitting a numerical solution of the model equation to the experimental data to obtain a practical value of the parameter. A parametric study on the gassing process of N2/CO2 mixture in membrane contactor was made with the help of the practical simulation model to investigate the effects of operation parameters on separation performance and to characterize the separation behavior of membrane contactor process. A series of simulations of the separation of N2/CO2 mixture in membrane contactor were conducted, and the optimization on the membrane process was discussed to maximize the separation performance in terms of N2 recovery percent in retentate and CO2 permeation rate. It was observed from the analysis of the result of the simulation that liquid flow rate has a negative effect on N2 recovery percent in retentate but a positive effect on the separation of CO2, while R-value affects the separation performance in the other way. It is confirmed in this study that the developed simulation can be used as a tool to optimize the parameters, i.e., feed gas pressure, liquid flow rate and R-value to maximize the separation performance

Mathematical Modelling of Intravenous Thrombolysis in Acute Ischaemic stroke: Effects of Dose Regimens on Levels of Fibrinolytic Proteins and Clot Lysis Time

Thrombolytic therapy is one of the medical procedures in the treatment of acute ischaemic stroke (AIS), whereby the tissue plasminogen activator (tPA) is intravenously administered to dissolve the obstructive blood clot. The treatment of AIS by thrombolysis can sometimes be ineffective and it can cause serious complications, such as intracranial haemorrhage (ICH). In this study, we propose an efficient mathematical modelling approach that can be used to evaluate the therapeutic efficacy and safety of thrombolysis in various clinically relevant scenarios. Our model combines the pharmacokinetics and pharmacodynamics of tPA with local clot lysis dynamics. By varying the drug dose, bolus-infusion delay time, and bolus-infusion ratio, with the FDA approved dosing protocol serving as a reference, we have used the model to simulate 13 dose regimens. Simulation results are compared for temporal concentrations of fibrinolytic proteins in plasma and the time that is taken to achieve recanalisation. Our results show that high infusion rates can cause the rapid degradation of plasma fibrinogen, indicative of increased risk for ICH, but they do not necessarily lead to fast recanalisation. In addition, a bolus-infusion delay results in an immediate drop in plasma tPA concentration, which prolongs the time to achieve recanalisation. Therefore, an optimal administration regimen should be sought by keeping the tPA level sufficiently high throughout the treatment and maximising the lysis rate while also limiting the degradation of fibrinogen in systemic plasma. This can be achieved through model-based optimisation in the future