Scale suspension

Varley, J. and Birch, J. 1999. Reactor design for large scale suspension animal cell culture. Cytotechnology 29(3), 177-205. 

Fig. 1.3 S mall scale oscillatory baffled reactor (OBR) for gram scale suspension polymerization.

On the industrial scale, suspension polymerizations are not only carried out in the aqueous phase, but also in aliphatic hydrocarbons using Ziegler-Natta catalysts, as for example, in the polymerization of ethylene and propylene (see also Sect. 3.3.1). 

Varley, J Birch, J. (1999). Reactor design for large scale suspension animal cell culture. Cytotechnology 29(3), 177-205. Wright, G. et al. (1991). High level expression of active human -antitrypsin in the milk of transgenic sheep. Bwj Technology 9, 830-834. 

Bree MA, Dhurjati P, Geoghegan R, Robnett B (1988), Kinetic modeling of hybridoma cell growth and immunoglobulin production in a large-scale suspensions culture, Biotechnol. Bioeng. 32 1067—1072. 

Microcarriers are small solid particles (kept in suspension by stirring) upon which cells may grow as a monolayer. They confer the advantage of large scale suspension cultures on anchorage dependent cells. They thus offer the following advantages. 

The use of small-scale suspension cultures is described in section 5.4. At some stage a decision has to be made, if scale-up is required, of when to move from laboratory units to small-scale industrial systems (Griffiths, 1992b). This is a decisive moment because of the investment needed to set up in situ fermentation systems. This step should be taken at 101 and involves ... 

PILOT-SCALE SUSPENSION CULTURE OF HYBRIDOMAS - AN OVERVIEW... 

J., Dabros, M., and Maurer, M. (2014) Yeast suspension culture, in Industrial Scale Suspension Culture of Living Cells (eds H. Meyer and D.R. Schmidhalter), Wiley-Blackwell. 

On a technical scale, suspension polymerization is nsed in the prodnction of polyvinylchloride, polystyrene, polymethyl methacrylate, and others. For the production of rnbbery, sticky, polymers (e.g., the polyacrylates), this is less snitable. 

As suspension polymerization is based on an in situ emulsification by turbulence, problems may arise during scale-up. The emulsification process is the real problem during the scale-up of laboratory-scale suspension polymerizations to an industrial level where today a typical reactor size is 200 m. ... 

The scale-up of suspension polymerization reactors (i.e., from lab to pilot and then to industrial scale) is not straightforward or well established. Probably, the most significant problem in scale-up occurs when different physical processes become Umiting at different scales. For example, commercial-scale suspension reactors have to perform several functions simultaneously (dispersion, reaction and heat transfer), which do not scale-up in the same manner. Thus, heat removal can become a Umiting factor for reactor performance at large scales while it is rarely a problem for lab-scale reactors [86]. 

For Rou > 4, the concentration level decreases very strongly on a vertical profile between two points spaced apart by a length equal to the integral scale suspension sustenance by turbulence is then weak. In contrast, if Rou < 0.5, the concentration level decreases by only 40% between its value at a given position and its value at a distance of one integral scale above. In the latter case, trrrbrrlence effectively maintains the particles in suspension. 

In small-scale suspension polymerization, inhibitors are often removed from the monomer before it is dispersed in the continuous phase. In large-scale operation, however, the inhibitor may not be removed. Its presence lowers the risk of premature polymerization, which can be dangerous when large amounts of monomer are being handled. Consequently, the particle size distribution obtained from the large reactor may differ from that in the small reactor because drop breakage can occur before significant amounts of polymer are formed (that is, when the drop viscosity is still relatively low). 

Laboratory-scale fermentations have been described elsewhere [2]. In this chapter, we lead the reader through the most important aspects of industrial-scale fermentation. Which organisms are suitable for large-scale suspension culture What do standard operating procedures (SOPs) and installations for large fermentation look like Which are the most important markets What affects the economics of large-scale fermentation, and which are the important regulatory aspects to be considered ... 

The first refers to mass cultivation and production by making use of cells in a highly controlled, closed bioreactor. Table 1.1 lists all cells and organisms that are available today for large-scale suspension culture. 

Nowadays, and as Table 1.1 shows, not only bacteria, yeasts, and fungi are cultivated in large-scale suspension culture. All the industrial manufacturing methods listed in Table 1.1 are described and discussed in much detail in a separate book [4]. Evidently, and as already mentioned earlier, the term large-scale or industrial-scale is a relative one. 

Although the cells and organisms listed in Table 1.1 differ greatly in taxonomy, form, size, and metabolism, there are four common elements that can influence the success of a large-scale suspension culture. 

Industrial Scale Suspension Culture of Living Cells... 

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