Multi-stage continuous high cell density culture systems: A review

Diffusion and Inhibition Processes in a Hollow-fiber Membrane Bioreactor for Hybridoma Culture. Development of a Mathematical Model

“…In a previous study carried out with the same cell line in T150-flasks containing 100 mL of protein-free medium 6 , it was observed that these substrates decreased only during the exponential growth phase. At the end of the experiment, the concentration of cells measured in the cartridge was 5·10 7 cell mL -1 , approximately a quarter of the concentration reported for the Alps 25-3 hybridoma cell line in the extra-capillary space of a dual hollow-fiber bioreactor 29 . Lactate and ammonium likewise increased throughout the experiment, as their production is associated with glucose and glutamine consumption.…”

“…In fact, a considerable amount of literature exists on the inhibitory or toxic effects resulting from lactate and ammonia accumulation in mammalian cell cultures 31 . Specifically, an inhibitory effect on cell growth and antibody production has been reported for these metabolic by-products 11,19,29 . The final antibody concentration was 0.22 mg mL -1 (approximately 4.4 pg cell -1 ).…”

“…29 For instance, Schneider et al 30 reported inhibition of glutamine uptake by elevated ammonia concentrations. Besides, it is a wellknown fact that accumulation of these cellular metabolism byproducts may inhibit hybridoma MAb production.…”

Volatile fatty acids derived from waste organics provide an economical carbon source for microbial lipids/biodiesel production

“…Although many batch or fed-batch cultures have been carried out for lipid production [6][7][8], bioreactor productivity was not high enough for viable commercial production. Multi-stage continuous high cell density culture (MSC-HCDC) is considered to be a fermentation technology that can lead to high productivity and titer for both extracellular and intracellular products [9,10]. High cell density culture fermentation gives a very high productivity because of its high cell density achieved by membrane cell recycling, or a moderate cell density attained by using a packed-bed combined with gravity settling [11][12][13][14].…”

“…Chang et al [9,19] reported that a MSC-HCDC system could give a 10 times higher productivity in terms of extracellular products (ethanol, lactic acid, monoclonal antibody, mAb) than a fed-batch culture while the product titer remained similar to that of fed-batch cultures. A single stage HCDC system yielded a very high productivity but a lower product titer [10,11,20]. In MSC-HCDC systems the strategy for producing intracellular products (poly-β-hydroxybutyric acid, PHB) and microbial lipids differs from those utilized to produce extracellular products.…”