Continuous Cultivation - Bioprocess Engineering: Kinetics, Biosystems, Sustainability and Reactor Design - page 609

Pump

Acid

Exhaust

Filter / sterilizer Pump PH

Feed

Filter

Turbidity

Rotameter

Effluent

Compressed air

FIGURE 12.2 Typical laboratory setup for a turbidostat.

device (chemostat). Chemostat is the continuous stirred-tank reactor (CSTR) as described in
Chapters 3 and 5, however, for cell culture applications. Cellular growth is usually limited by
one essential nutrient, and other nutrients are in excess. As we will show, when a chemostat
is at steady state, the nutrient, product, and cell concentrations are constant. For this reason,
the name chemostat refers to constant chemical environment (for cell culture).
Figure 12.2 is a schematic of a turbidostat in which the cell concentration in the culture
vessel is maintained constant by monitoring the optical density of the culture and controlling
the feed flow rate. When the turbidity of the medium exceeds the set point, a pump is acti-
vated and fresh medium is added. The culture volume is kept constant by removing an equal
amount of culture fluid. Therefore, turbidostat is a chemostat with a particular control mech-
anism, via the turbidity of the culture. As discussed in Chapter 11, cell concentration affects
the optical density and thus turbidity can be correlated to the cell concentration. Turbidostats
can be very useful in selecting subpopulations able to withstand a desired environmental
stress (for example, high-ethanol concentrations), because the cell concentration is main-
tained constant. The selection of variants or mutants with desirable properties is very
important.
A PFR can also be used for continuous cultivation purposes. Since there is no backmixing
in an ideal PFR, fluid elements containing active cells cannot inoculate other fluid elements at
different axial positions. Therefore, strict PFR is only applicable for fermentations where cells
are fixed along the reactor (immobilized and supported, for example packed beds). Liquid
recycle is required for continuous inoculation of nutrient media for cell growth cultivation.
In a PFR, substrate and cell concentrations vary with axial position in the vessel. An ideal
PFR resembles a batch reactor in which distance along the fermentor replaces incubation
time in a batch reactor as discussed in Chapters 4 and 5. In waste treatment, some units
approach PFR behavior, and multistage chemostats tend to approach PFR dynamics if the
number of stages is large (CSTR train, Chapter 5).