ABSTRACT

Efficient bioreactors are crucial to the successful manufacture of many high-value products, especially in the pharmaceutical industries. Stirred vessels are widely used even though the internal complexities of their behavior remain poorly defined and inadequately understood. For large vessels, the simplifying assumptions of perfect mixing or plug flow will certainly not apply when the bioreaction rates are fast relative to the internal mixing rates generated by rotating impellers. Such macro-mixing effects will tend to cause a partial segregation of batch-fed components in semi-batch operation. For typical fermenters, both oxygen in the gas phase as well as liquid phase nutrient steams, will be fed separately and (semi-) continuously as the manufacturing batch proceeds. Thus, gradients in dissolved oxygen in the liquid phase, as well as spatial variations in nutrient concentration, can be expected in practice.
Gas-liquid stirred vessel two-phase mixing accompanied by bioreaction has been analyzed using a 3-D networks-of-zones, in which non-axisymmetric phenomena can be included. The effect of the feed of liquid nutrient from a single dip-pipe can be incorporated so that previous 2-D limitations of axisymmetry are avoided.

The simulations can provide detailed predictions of the local gas hold-up distribution, the local mass transfer area, the partial segregation of both the dissolved oxygen and the nutrient and the extent of oxygen depletion of bubbles. The overall gas hold-up and mass transfer area are obviously summations of the local values and the local and overall reaction rates can be predicted as well as the local and overall oxygen absorption fluxes.
Simulations are presented for O(104) configurations of networks-of-zones for a 3 m3 triple-impeller industrial pilot-plant bioreactor. The theoretical predictions are demonstrated using color-augmented 3D contour maps and solid-body iso-surface images created by AVS graphics.
Severe non-uniformity of gas hold-up distribution with consequently spatially uneven oxygen mass transfer, create significant partial segregation of both oxygen and nutrient. Some bioreactors are predicted to be far from perfectly mixed, so that microorganisms will then experience large variations in dissolved oxygen and nutrient concentrations as they circulate with the fermentation broth.