Experimental simulation of large‐scale bioreaetor environments using a Monte Carlo method

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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.