| Abstract: | Cells grown in production-scale stirred bioreactors experience fluctuating concentrations due to local variations in supply and consumption of oxygen and nutrients. A new method for studying the effects of fluctuations in local conditions on growth and productivity of cells was developed using a Monte Carlo approach to simulate circulation within a fermenter. A small fermenter was driven through cycles of aeration and feeding, with the time of each cycle controlled by a Monte Carlo method to give a log-normal distribution. Experiments with Monte Carlo supply of air to batch and fed-batch cultures of Saccharomyces cerevisiae showed that the method gave reproducible results which were different from both periodic cycling and continuous supply. When substrate was provided to a fed-batch culture of S. cerevisiae according to the Monte Carlo method, the yields of biomass were higher than experiments with continuous feeding or periodic feeding. |
