D

Fig. 2.10. The effect of D on steady-state product concentration (p) and product output (Dp) when:

(a) qp is growth related.

ble that the technique could be exploited for other products provided strain degeneration is controlled; this may be possible in certain genetically engineered strains. It has been reported that the development of a continuous process for the manufacture of polyhydroxy-butyrate, a biopolymer. Other processes have been developed using chemostat culture.

The adoption of continuous culture for animal cell products is even more complex than for microbial systems. Griffiths (1992) compared the following process options for producing an animal cell product:

is difficult to monitor the genetic stability of cells wh' t are immobilized in a large reactor system. Thus ]-lr, scale (kg quantities) animal cell products are still n ^ duced by batch methods. However, where very hit value products are required and production can h satisfied on a small scale, the continuous perfusiy6 system is a very attractive proposition (Griffiths, ly^) Continuous brewing and biomass production which are the major industrial applications of continuous microbial culture will now be considered in more ri " tail.

(i) Batch culture.

(ii) Semi-continuous culture where a portion of the culture is harvested at regular intervals and replaced by an equal volume of medium.

(iii) Fed-batch culture where medium is fed to the culture resulting in an increase in volume (see later section)

(iv) Continuous perfusion where an immobilized cell population is perfused with fresh medium and is equivalent to an internal feedback continuous system.

(v) Continuous culture.

The characteristics of all five modes of operation are shown in Table 2.3, from which it may be seen that the perfusion continuous system appears extremely attractive. However, the practicalities of running a large scale continuous perfusion system present considerable difficulties. The process has to be reliable and able to operate aseptically for the long periods necessary to exploit the advantage of a continuous process. Also, the licensing of a continuous process may present some difficulties where a consignment of product must be traceable to a batch of raw materials. In a long-term continuous process several different batches of media would have to be used which presents the problem of associating product with raw material. Furthermore, it

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