Samaras, Jasmin Jade;
(2019)
Investigation of flow, mixing and suspension dynamics towards the optimisation of an iPSC-derived cardiomyocyte differentiation process in DASGIP bioreactors.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
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.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Investigation of flow, mixing and suspension dynamics towards the optimisation of an iPSC-derived cardiomyocyte differentiation process in DASGIP bioreactors |
| Event: | UCL (University College London) |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2019. Original content in this thesis is licensed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) Licence (https://creativecommons.org/licenses/by/ 4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Biochemical Engineering |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10069099 |
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