Delbridge, Jordan; (2024) A Comprehensive Characterisation of the Allegro™ Stirred Tank Bioreactor Towards Process Optimisation. Doctoral thesis (Eng.D), UCL (University College London).

Preview

Text Delbridge_thesis.pdf - Other Download (14MB) | Preview

Abstract

The development of new biopharmaceuticals relies on robust scale-up from small-scale screening studies to industrial bioreactors. Novel single-use bioreactor (SUB) designs can prove highly beneficial, although they lack the extensive characterisation of traditional stirred tank reactors (STRs). Cytiva’s Allegro™ STR 50-2000 L bioreactor range has a unique design of square cross-section, with three wedge-shaped baffles. A scale-down 1 L prototype (abbreviated A-STR) was developed for characterisation studies and compared to a standard cylindrical STR (abbreviated S-STR). Agreement of power and mixing number data with that of the Allegro STR 200 L indicated successful scale-down. In down-pumping mode, mixing times in the A-STR were approximately 53.0% lower than in the S-STR. However, in up-pumping mode (UP) both configurations exhibited similar mixing times. Four commercial microcarriers were assessed to determine the required impeller agitation rate and corresponding power input per unit volume to achieve homogenous microcarrier suspension. The A-STR operating in down pumping mode (DP) achieved homogenous suspension at considerably lower power input when compared to the other baffled configurations. For the A-STR (DP), the power input per unit volume demand was 67.8% lower than the A-STR in up-pumping mode (UP), 77.0% lower than the S-STR (DP) and 66.8% lower than the S-STR (UP). Flow structures investigated at the just-suspended condition, in the transitional regime, were in line with those presented in the turbulent regime at considerably higher Reynolds number. This implies that the normalised flow structures presented in this work at the just-suspended condition are representative of those in the commercial Allegro STR range, despite operating at significantly reduced scale and Reynolds number. Removal of baffles substantially reduced the power input required to achieve homogenous suspension in all configurations – other than the A-STR (DP), which exhibited relatively similar performance to the corresponding baffled configuration. Considering adherent cell sensitivity and mixing implications, and based on the results found in this work, the baffled A-STR (DP) is recommended for achieving microcarrier suspension at the lowest specific power input. Phase-resolved data were used for an in-depth analysis of flow in the A-STR geometry. In both UP and DP mode, the relative percentage of periodic kinetic energy was higher than that of the turbulent kinetic energy component in the unbaffled plane. Rotation of the impeller through the unbaffled and subsequent baffled planes appeared to disrupt the periodicity of the flow. Trailing vortex characterisation in UP mode showed the formation of two vortices – an upper counter-clockwise rotating vortex, and an axially lower clockwise rotating vortex of higher intensity. The clockwise rotating vortex exhibited higher intensity and inclination moving axially upwards. In DP mode, a single trailing vortex forms behind the blade tip and progresses towards the vessel base. Maximum periodic kinetic energy in UP mode was approximately two times greater than that in DP mode. Moreover, DP mode exhibited more homogenous distribution of turbulent kinetic energy throughout the tank bulk, in line with ensemble-averaged data. Estimation of the turbulent energy dissipation rate in UP mode illustrated that the phase resolved dissipation rate could reach approximately 56 times the mean value determined from impeller torque measurements. Despite this, the order of magnitude of the maximum dissipation rate remains well below dissipation rate thresholds for unwanted glycosylation profile changes or cell necrosis reported in literature for mAbs producing cell lines.

Download activity - last month

Export as XMLJSONCSV

Download activity - last 12 months

Export as CSVXMLJSON

Downloads by country - last 12 months

Export as XMLJSONCSV

Archive Staff Only

View Item