(A) study on internal-filtration system for continuous high cell density culture

Abstract

Among the options for high productivity in fermentation processes, bioreactor system development, as well as development of strains with high activity and optimization of operating conditions, are very important. In order to obtain high cell densities it is essential to retain cells inside the reactor as long as possible. For this purpose, cell recycle with internal membrane was adopted. All the ceramic filters used in this study for the internal filter system were tubular type and made by a sintering process. The average pore size of symmetric and asymmetric ceramic membrane was 0.3 and 0.005㎛ respectively. The pore size of stainless steel used in this study was 2㎛. For the optimum design of the internal membrane module, a relationship between the radius of the membrane tube and the ratio of the membrane surface per effective fermentation volume was worked out. It was found that there is an optimum dimensionless radius (r/R) in order to achieve the maximum ratio of the membrane surface area : fermentation volume. Factors affecting the permeation flux during the filtration of fermentation medium and broth by using a symmetric and an asymmetric ceramic membrane were investigated in an internal filter bioreactor. After sterilization of the fermentation medium the flux of the asymmetric membrane was 1.8 folds higher than that before sterilization. At 100g/l glucose, flux index (Fi) at steady state was only 21.8% for the asymmetric membrane and 42.2% for the symmetric membrane. When cell free broth was filtered, Fi at the steady state was 48% for the symmetric membrane and 21% for the asymmetric membrane. For the asymmetric membrane, a decline in the flux by nearly 80% was observed when 100g/l glucose and 8.5g/l yeast extract coexisted in the medium. The dual function of the cake layer during the filtration of the fermentation broth was investigated in depth and a mathematical model was also developed in order to describe the dual function of the cake layer qua...