Abstract
Scale-up was defined as “ The successful startup and operation of a commercial size of unit whose design and operating procedures are in part based upon experimentation and demonstration at a smaller scale of operation.” The aim of scale-up lies in saving time and lowering the cost via mass production. However, a fermentation process developed in the laboratory may not easily be scaled up to full production because it is difficult to assess certain factors affecting the scale up process. The combination of transport phenomena and kinetic behavior of microorganisms essentially governs the performance of a bioreactor. Both of these two factors are dependent on the scale of the bioreactor. As a result, many large-scale fermentation processes give a lower yield than is expected from laboratory scale experiments.This dissertation explores a method for scaling-up a fermentation system that is based on a series of special operations in a small-scale fermentor. It consists of two parts. The first part investigates the effects of the environmental state variables on the cultivation. If a wide range of the state variables has no significant effect on yield or productivity, scaling-up is not an issue in the fermentation system. If only a small range of the state variables has no substantial impact on cultivation, pulse or periodical change of the state variables would be carried out to investigate the effects of the change on cultivation.To illustrate the proposed method of scale-up, Bacillus thuringiensis was cultivated for thuringiensin production with the pH value as the environmental state variable. Different pH values at 7.0 and 8.4 had a significant effect on both cell growth and thuringiensin production. Variation of pH value for a short period of time did not have substantial effect on either cell growth or thuringiensin production. Therefore, if a large-scale fermentor had a short mixing time to make the variation of pH value lie within the limit, the environmental state variable, pH, did not result in the problem in the large-scale fermentor. On the contrary, when a large-scale fermentor can not provide a well-controlled condition for cultivation, design of the large-scale fermentor should be careful.A bioprocess system with mixed-growth-associated or non-growth-associated product should have the different cultivation conditions during the cell growth stage and production stage. Cultivation of Bacillus thuringiensis for thuringiensin production is a mixed-growth-associated system. Transient response technique -- variation of agitation speed and aeration during the exponential growth phase and stationary phase respectively was applied for investigating the effect of shear stress on cultivation of B. thuringiensis for thuringiensin production. It was found that shear stress had little effect on product formation but the concentration of dissolved oxygen in the broth played a much more significant role during the exponential growth phase. However, shear stress had a substantial effect on thuringiensin production during the stationary phase. By decreasing the agitation speed during the stationary phase, the product formation could increase up to 43%. This provided an important information in cultivation of B. thuringiensis for thuringiensin production.