Crt

'disks

'printer le rmen te r controller

Figure 11. General control system of batch fermenter.

Table 10. Limiting Factors of High Density Cell Cultivation[37]

Limiting factors:

Physical factors: Shear force

Physiological factors: Accumulation of chalone-like substances Contact inhibition

Chemical factors: Exhaustion of nutrient

Decrease of dissolved oxygen Accumulation of ammonium ion Accumulation of lactate

2.4 Perfusion Culture Systems as a New High Density Culture

Technology

In monolayer cultures, Knazeck et al.[36] have shown that an artificial capillary system can maintain high density cells using perfusion culture. The artificial capillary system is very important when cell densities approach those of in vivo values obtained via in vitro culture systems. Perfusion culture systems are continuous culture systems that are modelled after in vivo blood flow systems. In perfusion culture systems, a continuous flow of fresh medium supplies nutrients and dissolved oxygen to the cultivating cells. Inhibitory metabolites such as ammonium ions, methylglyoxal, lactate and high molecular chalone-like substances are then removed automatically. If the cells cultivated under continuous flow conditions can be held in the fermenter membranes, filters, etc., then the cells can grow into high density by the "concentrating culture." Thus, these perfusion culture systems may be able to solve some of the limiting factors associated with high density cell growth such as the mouse ascites level.

The perfusion culture systems are classified into two types by static and dynamic methods as shown in Fig. 12.

Hollow fiber Ceramic opticore Membroferm

Suspension & perfusion culture system

Membrane dialysis

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Membrane agi ta tor xn!

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