Microfluidics-based bioprocessing platform for high-throughput cell and gene therapy manufacturing applications

Re-programming a patient's own cells to combat degenerative diseases using cell and gene therapies (CGT) is now possible, given the success of Novartis Kymriah immunotherapy. However, the costs of such treatments remain exorbitantly high, thereby constraining the NHS to restrict its use to a limited number of patients. The expensive costs reflect the current state-of-the-art - a slow manufacturing and development process from discovery to commercialisation coupled with the necessity to use multiple equipments to perform different processes. Thus, the bottleneck exists between production and accessibility, which can be alleviated by developing a robust, scalable and closed manufacturing platform that can enable safe, low-cost treatments, and rapid development time.

Our primary goal is to develop a high-throughput bioprocessing platform based on microfluidics technology. Microfluidics - the science of microscale fluid manipulation - addresses the challenges of streamlined, high-throughput cell production by optimising fluid consumption during cell expansion. The cell culture will be performed in multi-functional microfluidic chips, which is capable of performing all the necessary standard processes for CGT (e.g. seeding, perfusion, harvest) in situ in a sealed non-invasive environment.

The over-arching objectives for each PhD years are:

First year: Training in microfluidics and microfabrication skills; optimisation of key chip design parameters (e.g. flow rates, channel dimensions) using experimental and numerical modelling (Comsol Multiphysics) of various parameters; Hydrodynamics of chip parallelisation

Second/Third year: Biological testing of prototype chip with relevant cell types (human lines and primary) to obtain data for cell characteristics (e.g. survival, proliferation, morphology, phenotype, differentiation, activation); Results will be compared with conventional methods

Third/Fourth year: Integration of biological testing with high-throughput chip parallelisation.