Multiphase Bioreactor Design

equivalent two-liquid phase reactor has been proposed, known as the liquid-impelled loop
reactor (van Sonsbeek et al., 1993). Clearly such a reactor has the difficulty that the
density difference between the two liquid phases is small relative to gas and liquid
density differences and this makes the separation zone at the end of the reactor difficult to
design. This problem is made worse by the presence of emulsifying agents, either
secreted from cells or present in solution. Such reactors are also not available
commercially.
Examples of membrane reactors used with two-liquid phase biocatalytic systems fall
into two categories, those using microporous membranes and those using dense-phase
membranes. In both cases the aqueous and organic phases are kept apart by the
membrane in order to overcome problems of emulsion formation. With microporous
membranes, breakthrough of either liquid phase is prevented by careful control of the
transmembrane pressure (Prazeres and Cabral, 1994) and solute mass transfer coefficients
are typically in the range 0.17−1.67×10−^5 m s−^1 (Molinari et al., 1997). Industrial
installations of this type have emerged for the production of diltiazem with an installed
membrane area of 1440 m^2 and a productivity of 75 kg yr−^1 m−^2 (Lopez and Matson,
1997). The use of nonporous, dense-phase membranes, such as silicon, has recently been
explored in order to overcome the need to carefully control the transmembrane pressure
(Doig et al., 1998). Here solute transfer occurs by a solution-diffusion mechanism and
overall mass transfer coefficients in the range 0.1−2.1×10−^5 m s−^1 have been determined.
The main disadvantages of both types of membrane reactor are the low solute mass
transfer coefficients (and hence the large membrane areas required) and fouling of the
membrane surface over extended periods of operation (Prazeres and Cabral, 1994;
Westgate et al., 1998).

Mass Transfer and Reaction Kinetics

Clearly intimate contact of the aqueous and organic phases is necessary in order to
effectively transfer reactants and/or products from one phase to the other. Considerable
work has been done to examine these issues in the past and in the majority of systems
studied mass transfer was not found to be limiting. In particular, whole-cell catalysed
reactions are slow and therefore mass transfer is not likely to be a problem. Where
solvents are used with a very high viscosity individual mass transfer coefficients will be
reduced which may cause problems. In contrast, reactions catalysed by isolated enzymes
(usually immobilised to assist with downstream processing) may display mass transfer
limitations when the catalyst has a high specific activity. Such effects will be dependent
on the Michaelis constant of the enzyme. If the Michaelis constant is very low relative to
the aqueous phase saturation concentration of substrate then the effectiveness factor (i.e.
the observed reaction rate in a two-phase system divided by the reaction rate in a single
phase system) will still be high. It is interesting to note that in a number of cases
examined to date we have found the Michaelis constant of the enzymes to be a fraction of
the aqueous phase saturation concentration. Figure 5.3 illustrates typical data for three
such systems.
Figure 5.4 shows a general mass transfer-reaction model for the case of a
transformation occurring in the bulk of the aqueous phase and a biocatalyst which
exhibits normal Michaelis-Menten kinetics. This describes the change in both substrate

Multiphase bioreactor design 130