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Scaling-Up from Spinners, T-Flasks & Shakers: A versatile bioreactor for mammalian and microbial cells

ten operated in perfusion mode, allowing for continuous addition of fresh nutrients with continuous harvesting of secreted products. However, the longer the run, the greater the risk of contamination. Therefore, mammalian cell culture bioreactors require added contamination safeguards, such as use of magnetic-coupled bearing housings and threadless welded ports among others.

Temperature - Microbes have a wide range of temperature tolerances, with strains found in the sub-freezing environs of the North Pole, as well as in ocean vents at temperatures in excess of 100C. Mammalian cells, meanwhile, tolerate only a very narrow temperature range, typically between 37C and 42C. Microbial fermentors, therefore, usually control temperature to within 1C, while mammalian cell bioreactors require regulation capabilities within 0.1C.

pH - The acidity level of the culture medium is expressed by pH, with microbes thriving in conditions with a typical range of 2 - 10 pH depending on the microorganism, and mammalian cells requiring a pH level of 6.8 - 7.2. The method and responsiveness of the control significantly influence the process.

Acid and base addition is the method of choice for pH control of microbial cultures. Typically, a pH sensor linked with the fermentors internal controller signals it to activate a peristaltic acid or base pump. Not all fermentors handle the pH setpoint and deadband control in the same manner. An improper deadband setting can cause an action-reaction scenario, in which the pH overshoots the maximum limit activating one pump after another, leading to oscillation and unstable pH control. Since cells derive their nutrients from the transport of culture medium components through their walls, if the medium fluctuates between acidic and alkaline conditions, the cells will stop taking-up nutrients and eventually starve to death. The fermentor controller
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