Engineering characterisation of single-use bioreactor technology for mammalian cell culture applications

The thesis describes an experimental investigation of the fluid dynamics within novel single-use bioreactors (SUBs), including stirred, rocked and pneumatically driven mixing systems. Biological studies to ascertain the impact of hydrodynamic conditions within these systems, on the growth and protein productivity of a mammalian cell line, are also presented. Two-dimensional velocity measurements within different SU technology were acquired with the use of a whole flow field laser-based technique, Particle Image Velocimetry (PIV). Fluid dynamic characteristics including velocity, turbulence, turbulent kinetic energy and vorticity were determined from time-resolved and phase-resolved velocity measurements. Commercial bioreactor systems were modified, if needed, in order to perform experiments within bioreactors commonly used for cell culture experiments, in preference to using vessel mimics. The fluid flow characteristics in both the impeller region and bulk fluid of a single-impeller stirred bioreactor were investigated, facilitating an enhanced understanding of the spatial distribution of velocity and turbulence throughout the vessel. PIV was also used to study the flow in a dual-impeller stirred bioreactor, providing a rare examination of the interaction between the flow fields generated by two impellers. The whole flow field velocity and turbulence characteristics measured within a rocked bag and pneumatically driven vessel, allow a unique insight into the flow pattern and turbulence distribution within two novel cell culture systems. Cell viability, size, growth, protein productivity and metabolites concentration were monitored under different cell culture operating conditions. Cell culture experiments, combined with the hydrodynamic information acquired using PIV, offer an insight into the physiological response of the cells to highly disparate flow conditions. This information helped to understand how the hydrodynamics induced by novel commercially used mixing systems, can impact upon a mammalian cell line. Having implications for an augmented capacity for cross-compatibility, in addition to enhanced strategies for scale translation and optimal bioreactor design