This thesis focused on the development of ultra scale-down (USD) approaches to predict dewatering levels of high cell density yeast cell suspensions in centrifuges. Two yeast cell and feed types were used: Baker’s yeast suspensions and P.pastoris fermentation cultures. P.pastoris was grown to high cell densities equivalent to that obtained in industry (2 100 g/L DCW). Two methodologies were successfully developed and verified at scale (p-value 2 0.05). A small-scale (~ 15mL) USD methodology was described to mimic dewatering levels of two pilot-scale centrifuges with intermittent solids discharge, a tubular-bowl CarrpowerfugeTM P6 centrifuge and a disc-stack CSA-1 machine, in ready available laboratory centrifuge tubes. This was followed by a separate USD device, designed to recreate dewatering conditions in a continuous solids discharge pilot-scale centrifuge, in particular a scroll decanter centrifuge (SDC), at very small scale (2 mL). The basis of both USD approaches was to use a feed concentration that would mimic the maximum final height of wet solids experienced in the pilot-scale machine; and to use the same range of equivalent residence times (Gt) practised at pilot-scale. The USD device simulated two different dewatering operations that occurred in a SDC: compression and decanting. The validation of the use of this USD device was successfully undertaken with high cell density Baker’s yeast suspensions (p-value 2 0.05). Finally, the first developed USD methodology was further used on a case study where the impact of the choice of P.pastoris cell strain during fermentation was assessed on centrifugation performance. This work therefore presented simple and novel methodologies that were performed in the laboratory and that required small quantities of feedstock material (~ 1 5ml) hence reducing the need for repeated pilot-scale runs during early stages of bioprocess development.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:626216 |
| Date | January 2013 |
| Creators | Lopes, A. G. |
| Publisher | University College London (University of London) |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://discovery.ucl.ac.uk/1396241/ |
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