Multiphase Bioreactor Design

2. the relation between kinetics and dynamic behaviour of the bio-systems of interest;
   and


3. the behaviour of the physical systems in which the bio-processes take place.

A never-ending comment in bioprocess engineering is the following: “Due to the lack of
appropriate monitoring techniques and due to the bad predictability of bioprocesses we
need to...”. This is complemented by a final affirmative part which varies. It ranges from
“...use fuzzy models and expert systems” over “...eliminate the anyhow too complex
kinetics” to “...control the feed rate optimally”. Certainly, there is a large grain of truth in
the first part of the statements. Those different closing comments indicate that there are
no unique solutions. The issues related to measurement, modelling and control, of course,
gives rise to many controversial discussions. Several of these issues will be discussed in
the following sections of this paper.

BIOREACTOR MONITORING

Measuring Techniques

pH

pH is one of the variables often controlled in bioprocesses operated in bioreactors
because enzymatic activities and, therefore, metabolism is very sensitive to pH changes.
The acidification derives—in most cases—dominantly from the ammonia-uptake when
ammonium ions are provided as nitrogen source: NHs is consumed and the proton left
over from the NH+ 4 contributes to the pH-drop.
pH of process suspensions is measured potentiometrically using electrodes filled with
liquid or gel electrolytes. Glass electrodes develop a gel layer with mobile hydrogen ions
when dipped into an aqueous solution. pH changes cause ion diffusion processes
generating an electrode potential. Lithium rich glasses are well suited for this purpose.
The potential is measured in comparison to a reference electrode which is usually a
Ag/AgCl-system since kalomel would decompose during sterilisation (strictly speaking
above 80°C). The electric circuit is closed via a diaphragm separating reference
electrolyte from solution. Since the diaphragms are known to be prone to fouling,
electrodes without diaphragm are currently under development.

Pressure

The direct dependence of micro-organisms on pressure changes is negligible provided
they do not exceed many bars. But indirectly, the partial pressure of dissolved gases and
their solubility is affected and must, therefore, be at least considered if not controlled. A
data sampling frequency in the range of a few 100 ms is appropriate for direct digital
pressure control (DDC) in laboratory scale bioreactors.

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