Continuous culture, application

Despite the advantages of continuous cultures, the technique has found little application in the fermentation industry. A multi-stage system is the most common continuous fermentation and has been used in the fermentation of glutamic add. The start-up of a multi-stage continuous system proceeds as follows. Initially, batch fermentation is commenced in each vessel. Fresh medium is introduced in the first vessel, and the outflow from this proceeds into the next vessel. The overall flow rate is then adjusted so that the substrate is completely consumed in the last vessel, and the intended product accumulated. The concentration of cells, products and substrate will then reach a steady state. The optimum number of vessels and rate of medium input can be calculated from simple batch experiments. 

J. Monod, Continuous culture technique. Theory and applications, Ann. Inst. Pasteur Paris 1950, 79, 390-410. 

Representative applications Sterile filtration Clarification/sterilization of beer and Representative applications Continuous culture/cell recycle Filtration of oilfield produced water... 

Because of the need to avoid mutations and maintain the superior qualities of the genetically developed strain, batch or fed-batch operations are used in most applications. Continuous culture operations, however, provide a time-invariant environment that facilitates greatly the study of a biological process in research laboratories. Moreover, some industrial operations employ continuous reactors, such as the single-cell protein facility of ICI in Billingham, England (total reactor volume of about 2,300 m3), all waste treatment processes, and others. It should be noted that it is relatively common to follow a batch process with a period of fed-batch or continuous operation. Also, in most cases batch cultivation is the optimal start-up procedure for continuous or fed-batch cultivation (Yamane et al, 1977). 

Cartridge and membrane filter systems tested in preliminary studies in our laboratories have proved to be applicable to eukaryotic cell culture processes, i.e. cell removal, semi-continuous culture growth, cell culture concentration and recycling. Present membrane systems are limited in processing volume cartridges are scalable, but have a narrower range of application. 

The situation is different when simulating the dynamics of the uptake of the carbon and energy source. Here, there is a high risk of failure if the dynamic behavior is predicted with Monod kinetics verified at different snapshot steady states in continuous or fed batch cultures. Application of these kinetics is questionable, because the steady state data of substrate uptake at different dilution rates may be corrupted by induction of different transporter systems depending on the steady state substrate concentrations. In addition to the variability of the affinity of the various transporter systems as clearly demonstrated for the yeast Saccharomyces cerevisiae, we do expect pronounced differences between permeases and phospho-transferase systems because of the clear distinctions in the influence of intracellular metabolites upon the uptake dynamics. 

Application of calorimetry to oxygen-limited continuous cultures has been presented in detail in references [67,71,72]. In fact, reductive metabolism is almost athermic as compared to aerobic metabolism. In addition, it is possible to set the oxygen limitation to the desired value by changing the oxygen gas feed composition [67,73]. The level of oxygen limitation is quantified by the ratio PoiKi (called aerobicity and also denoted Q [74]) ... 

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