INGENIEUR
purification of vaccine containing material 4 . The process design is based on laboratory procedures where culture growing , purifying and transferring are carried out in shake flasks ( See Figure 1 ) and roller bottles 5 placed on shaker incubator racks to support cell growth . Roller bottles are , however , only scalable in numbers but not in size , which poses a difficulty for process control and automation . Small scale stirred vessel bioreactors are now used in the laboratories to enable parallel control of parameters for optimisation and for ease of scale-up with the same configuration ( see Figures 2a to 2-d ).
Bioreactors are essentially containers that provide the ideal environment for the growth of bacterial , yeast or mammalian cells . The cells can be in free suspension as in the case of microbial cells , or anchorage-dependent ( adherent ) as is common for animal / mammalian cells . Anchoragedependent cells are grown on microcarriers made of porous resin beads which are suspended in the bioreactor ( see Figure 3 ). Free suspension allows for better contact area between the cells and the medium to maximise nutrient mass transfer into the growing cells , or in the case of enzyme reactors , contact among reactants .
Providing the right environment entails good temperature and pH control , availability of nutrients , and oxygen for aerobic systems . These are influenced by the bulk fluid momentum , energy imparted into the system , and eddy formation at micro level , all of which depend on efficient mixing of the bioreactor content .
The stirred vessel is the go-to configuration for reactors , for its versatility in mixing capability . Comprising essentially a vessel with one or more impellers mounted on a shaft run by a motor , there are numerous ways in which the stirred vessel itself can be configured to best suit the need of the process system .
Figure 1 : Laboratory vaccine development experiments in shakeflasks ( photo courtesy of UM TIDREC )
STRs are usually made of glass or stainless steel . The vessels are designed in cylindrical shape to comply with pressure-vessel standards for enhanced mechanical strength . In biological systems the bioreactor and ancillaries operate in a sterile environment . More recently , singleuse or disposable systems have been developed as an alternative to reusable , sterilisable ones . Single-use systems eliminate the cleaning step , avoid contamination risks , reduce capital costs and improve productivity . 6 Interestingly , due to logistic reasons and manufacturing practices , the favoured vessel shape for single-use bioreactors is a cubical shape . 6
Mixing and Hydrodynamics
The chemical engineering approach to the design and selection of unit operations equipment is to look at a system from the perspective of its physical properties namely , the phases involved – liquid , solids and gas , density , density differences , viscosity , particles size , and dimensions relating to reactor geometry . This approach is practical considering the very wide range of applications
34 VOL 86 APRIL-JUNE 2021