Three phase hollow fiber bioreactors for aerobicwhole cell immobilization

Abstract

In this study newly designed hollow fiber bioreactors for aerobic whole cell immobilization were introduced. First, the dual hollow fiber bioreactor consisting of outer silicone membrane for oxygen transport and three inner isotropic polypropylene hollow fibers for liquid nutrient transport were designed and its performance was examined by cultivating the aerobic microbes such as E. coli, Nocardia mediterranei, Aspergillus niger and Streptomyces griseus (chapters 2-6). Second, aerobic hollow fiber bioreactors with internal aeration circuits were newly designed and their performance was examined by cultivating the fungus, Aspergillus niger, producing citric acid. In chapter 2, the dual hollow fiber bioreactor carried out by simulation. Oxygen penetration depth and volumetric oxygen uptake rate were not much affected by the silicone membrane thickness and a major portion of oxygen transfer resistance existed in the immobilized cell layer. In chapter 3, the cell density and packing characteristics of E. coli in a dual hollow fiber bioreactor were investigated. The cells have grown forming the layer like animal tissue in a nearly 100\% packing density. The dry biomass density was 550 gram/liter of void volume for cell growth, which was the highest among the biomass densities ever reported. In chapter 4, continuous production of rifamycin B was studied using Nocardia mediterranei immobilized in a dual hollow fiber bioreactor. In the reactor operation the volumetric productivity based on the volume occupied by the immobilized cells was $108 mg/L\cdot h$ when air was used for aeration and was $143 Mg/L$. with pure oxygen. These corresponded to 22 and 30-fold increase over the productivity of the comparable batch system. However, the specific productivity of the cell was 30-40\% of that in shake-flask culture. These high volumetric productivities were due to the high cell mass density of 550 gram/L. As the residence time of medium in the reactor increased, pH of the ef...