Predictive scale up in mini and micro bioreactors screening

One well known drawback of shake flask culture is its limited surface aeration and atmospheric gas exchange.  Ultimate enhancement of oxygen transfer in shaker culture relies on atmospheric oxygen enrichment or culture volume reduction or both.  They soon made high throughput studies of micro-bioreactors cultures a success as soon as the micro-titer-plates and its readers became available.  Like shake flask, their shortcoming in scale up remains with the unrealistic surface aeration, and cannot be resolved simply by a matching k_La – mass transfer coefficient k_L, multiplied by total gas-liquid interfacial area, a.  On the other hand, impeller dispersed line gas sparging in larger scale stirred tank reactor (STR) is not easily scale down to or reproduced in mini and micro scale vessels like shake flask or micro titer plate without compromising their advantage in simplicity and economy.  As success of combinatorial DNA reconstruction and its subsequent high volume phenotype screen and validation spreads in recent decade, predictive scale up, like realistic up-scale stirring, gas-liquid mixing and gas phase oxygen and carbon dioxide partial pressures, in mini or micro scale reaction vessels has driven the high throughput fermentation screening device market ever since.  This presentation will go over pros and cons of recent mini jar (in 10-100s mL) and micro well (in 100s µL) bioreactors in gas-liquid mixing design, and how they must be improved and adopted for high throughput process validation and predictive scale up screen in your everyday microbiology laboratory.