Multiphase Bioreactor Design

detection principle allows simultaneous monitoring and consequently control of
important metabolites.

Biosensors

The rational for using biosensors is to combine the high specificity of biological
components with the capabilities of electronic tools (i.e. “usual” sensors). Biosensors
consist of a sensing biological module of either catalytic (e.g. enzymes, organism) or
affinity reaction type (e.g. antibodies, cell receptors) in intimate contact with a physical
transducer. The latter converts the chemical finally into an electric signal. Co-
immobilisation of enzymes can be advantageous when compared to sequential operation.
In general, the bio-part of the biosensor cannot be sterilised.
Electrochemical transducers work based on either an amperometric, potentiometric, or
conductometric principle.
Optical biosensors typically consist of an optical fibre which is coated with the
indicator chemistry for the material of interest at the distil tip. The quantity or
concentration is derived from the intensity of absorbed, reflected, scattered, or re-emitted
electromagnetic radiation (e.g. fluorescence, bio-and chemiluminescence). Usually,
enzymatic reactions are exploited.
Another type of biosensors exploits the fact that enzymatic reactions are exothermic (5
to 100 kJ mol−^1 ). The biogenic heat can be detected by thermistors or temperature
sensitive semiconductor devices.
The piezo-electrical effect of deformations of quartz under alternating current (at
frequency in the order of 10 MHz) is used by coating the crystal with a selectively
binding substance, e.g. an antibody. When exposed to the antigen, the antibody-antigen
complex will be formed on the surface and shift the resonance frequency of the crystal
proportional to the mass increment which is some way, but not necessarily linearly
proportional to the antigen concentration.

Time aspects

A notorious underestimation of the dynamic properties of microbial and cellular
populations results from matching the duration of the respective batch cultivations to the
relevant time constant of the biosystem under investigation. However, metabolic
regulation of enzyme activities and fluxes often takes place in the time scale of seconds
rather than days although the latter may be true as well.
The relaxation time concept of Harder and Roels (1982) maps typical time constants
of microbial and cellular control on the level of modification of enzymes (activation,
inhibition, dis/association of subunits, covalent modification or digestion) to the range of
ms to s, on the level of regulation of gene expression (induction, repression or
derepression of transcription) to min and on the level of population selection and
evolution to d and larger units.
The dynamics of microbial cultures has important impacts on the characteristics of
measurement and process control. The “typical time constant” in a bioprocess is often
erroneously anticipated to be equivalent to the entire duration of a cultivation.

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