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Title: Investigation of flow, mixing and suspension dynamics towards the optimisation of an iPSC-derived cardiomyocyte differentiation process in DASGIP bioreactors
Author: Samaras, Jasmin Jade
ISNI:       0000 0004 7661 122X
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2019
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This thesis describes an experimental investigation of the flow, mixing and suspension dynamics within DASGIP stirred tank bioreactors, including flat and round-bottom geometries, utilising a range of agitation modes to improve understanding of the impact of continuous and intermittent agitation upon an induced pluripotent stem cell-cardiomyocyte (iPSC-CM) cell culture process. Commonly used for cell culture applications, the DASGIP bioreactor has not fully been characterised and the beneficial impact of modifying the agitation mode on cell culture has also not been fully investigated from an engineering perspective. In the present study, rigorous flow frequency analysis with iPSC differentiation experiments were performed such as to identify and quantify the flow characteristics leading to increased cardiomyocyte differentiation yields with different agitation modes. Intermittent agitation resulted in a pattern of low intensity frequencies at reactor scale that could be controlled by varying three identified time components: rotational speed, interval and dwell time. A proof of concept biological study was undertaken, tuning the hydrodynamic environment through variation of dwell time and a significant improvement in CM yield was obtained. Ensemble-averaged and phase-resolved Particle Image Velocimetry measurements were carried out in a single-phase flow to evaluate the impact of the changing agitation modes and bioreactor configuration. Suspension and mixing time studies were undertaken to assess the impact of the agitation mode on quality of suspension and mixing time. It was found that the flat bottom geometry of the DASGIP resulted in a strong lower vortical cell below the impeller, resulting in efficient 'lift' of various microcarrier types. The application of intermittent agitation resulted in an overall transient amplification of shear stress and turbulence, found to beneficially impact upon the characteristic mixing times, whilst remaining around 100-fold lower to shear stresses found in literature to detrimentally impact upon stem cell culture proliferation and viability.
Supervisor: Micheletti, M. ; Ducci, A. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available