Multiphase Bioreactor Design

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al., 1997). Table 14.1 summarises current commercial/near commercial processes
involving plant cell suspensions.
From an engineering perspective, the successful application of plant cell suspensions
requires large-scale processing technology which supports high-density cultivation of
high-yielding, stable cell lines. The processes identified in Table 14.1, coupled with
additional, non-commercial, large-scale (>500 L) applications in Table 14.2, clearly
illustrate the feasibility of this approach. However, given the diversity of phytochemicals,
the range of cell lines and products involved is extremely limited. Cost factors clearly
account for the modest exploitation of this inherently capital intensive technology.
Economic analyses indicate the commercial viability of cell culture for the production of
speciality chemicals (Verpoorte et al., 1991; Sahai, 1994) and, assuming significant
advances in system productivity and processing technology, of food and food ingredients
(Goldstein, 1999). However, the absence of a consistent, broad-based approach to process
design and scale-up indicates that there are still engineering challenges to be met.
This chapter takes a practical approach to engineering aspects of bioreactor design for
plant cell cultures. The reader is also referred to other, comprehensive studies of this
topic (Payne et al., 1991; Doran, 1993; Singh and Curtis, 1994a). Only suspension
cultures are considered here; tissue cultures, organ cultures and immobilised systems are
covered elsewhere (e.g. Payne et al., 1991; Doran, 1997; Singh and Curtis, 1994b).
Where possible, reference is made to large-scale applications, although details of such
processes are still generally proprietary.


CHARACTERISATION OF PLANT CELLS AS BIOCATALYSTS

Many of the operational difficulties encountered with the scale-up of plant cell
suspensions stem from the physical and physiological characteristics which distinguish
plant cells from the microbial systems for which submerged cultivation technology was
originally developed. As is apparent from Table 14.3, the most significant differences
between plant cells in suspension cultures and microbial cells are in terms of cell size,
shear sensitivity and growth rate. These three factors, coupled with broth rheology, which
is significantly influenced by cell size and shape, impact directly on the engineering and
commercial feasibility of cultivation in large-scale bioreactors. However, broad
characterisation of plant cell suspension cultures is complicated by considerable
variations between the performance of different cell lines and even, of the same cell line,
under different cultivation conditions. Indeed, variability is a very important issue for the
commercial application of cell suspension technology and has been identified as the most
problematic factor for the use of Taxus cell cultures for paclitaxel production (Ketchum
et al., 1999).


Morphology

In suspension culture, single plant cells are typically of the order of 10–100 μm in size,
varying in shape from broadly spherical to cylindrical. Figure 14.1 shows micrographs of


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