Stirred-Tank Bioreactor

Bioreactors a) batch stirred tank b) continuous stirred tank c) continuous packed-bed i) downward flow, ii) upward flow and iii) recycle d) continuous fluidised-bed e) continuous ultrafiltration. Redrawn from Katchalski - Katzir E. (1993) Trends in Biotechnology II, 471-477. 

The mass transfer, KL-a for a continuous stirred tank bioreactor can be correlated by power input per unit volume, bubble size, which reflects the interfacial area and superficial gas velocity.3 6 The general form of the correlations for evaluating KL-a is defined as a polynomial equation given by (3.6.1). 

Fig. 4.1. Instrumentation control for continuous stirred tank (CSTR) bioreactor.

Stirred tank reactor the most common type of bioreactor used in industry. A draught is fitted which provides a defined circulation pattern. 

The design emphasis of this section will be on stirred tank bioreactors, which are the most common type used commercially in many bioprocess industries. 

The typical bioreactor is a two-phase stirred tank. It is a three-phase stirred tank if the cells are counted as a separate phase, but they are usually lumped with the aqueous phase that contains the microbes, dissolved nutrients, and soluble products. The gas phase supplies oxygen and removes by-product CO2. The most common operating mode is batch with respect to biomass, batch or fed-batch with respect to nutrients, and fed-batch with respect to oxygen. Reactor aeration is discussed in Chapter 11. This present section concentrates on reaction models for the liquid phase. 

The main part of the report describes the results of systematic investigations into the hydrodynamic stress on particles in stirred tanks, reactors with dominating boundary-layer flow, shake flasks, viscosimeters, bubble columns and gas-operated loop reactors. These results for model and biological particle systems permit fundamental conclusions on particle stress and the dimensions and selection of suitable bioreactors according to the criterion of particle stress. 

The aim of this report is to examine the principles of shear stress on particles that would allow the design of bioreactors for technical use, mainly stirred tanks, bubble columns and loop reactors. 

Special reactors are required to conduct biochemical reactions for the transformation and production of chemical and biological substances involving the use of biocatalysts (enzymes, immobilised enzymes, microorganisms, plant and animal cells). These bioreactors have to be designed so that the enzymes or living organisms can be used under defined, optimal conditions. The bioreactors which are mainly used on laboratory scale and industrially are roller bottles, shake flasks, stirred tanks and bubble columns (see Table 1). 

The power input in stirred tanks can be calculated using the equation P = Ne pnM if the Newton number Ne, which at present still has to be determined by empirical means, is known. For stirred vessels with full reinforcement (bafQes, coils, see e.g. [20]), the only bioreactors of interest, this is a constant in the turbulent flow range Re = nd /v> 5000-10000, and in the non-aerated condition depends only on geometry (see e.g. [20]). In the aerated condition the Newton number is also influenced by the Froude number Fr = n d/g and the gas throughput number Q = q/nd (see e.g. [21-23]). 

Many interesting biocatalytic reactions involve organic components that are poorly water-soluble. When using organic-aqueous biphasic bioreactor, availability of poorly water-soluble reactants to cells and enzymes is improved, and product extraction can be coupled to the bioreaction. Many applications in two-phase media can use the existing standard-type bioreactors, such as stirred-tank, fluidized-bed, and column reactors with minor adjustments. 

Mammalian cell suspension cultures are the preferred choice for large-scale recombinant protein production in stirred-tank bioreactors. The most widely used systems are Chinese hamster ovary (CHO) cells and the murine myeloma fines NSO and SP2/0. In half of the biological license approvals from 1996-2000, CHO cells were used for the production of monoclonal antibodies and other recombinant glycosylated proteins, including tPA (tissue plasminogen activator) and an IgGl fusion with the tumor necrosis factor (TNF) receptor, the latter marketed as Enbrel [7]. 

Stimuli-responsive materials, shape-memory polymers as, 22 355-356 Stirling cycle, 8 43 Stirred autoclave, 14 89, 92t Stirred autoclave reactor, 20 216 Stirred batch RO unit, 21 644 Stirred mills, 16 615 Stirred tank bioreactors, 1 737-740 oxygen transfer driving force, 1 734 Stirred tank electrochemical reactor (STER), 9 660-662... 

Fermentation systems obey the same fundamental mass and energy balance relationships as do chemical reaction systems, but special difficulties arise in biological reactor modelling, owing to uncertainties in the kinetic rate expression and the reaction stoichiometry. In what follows, material balance equations are derived for the total mass, the mass of substrate and the cell mass for the case of the stirred tank bioreactor system (Dunn et ah, 2003). 

Production. The inoculum grew vigorously in the rich yeast extract containing media and produced a thick viscous dispersion in the stirred tank bioreactor. No lignin peroxidase activity could be detected at this stage. When transferred to the 1000 1 production bioreactor, the mycelium of P.chrysosporium attached completely to the nylon wool sheets within a few hours after inoculation and the medium remained completely clear throughout the cultivation. The enzyme had to be harvested immediately after the maximal activity level was reached due to its... 

Industrial hazardous wastewater can be treated aerobically in suspended biomass stirred-tank bioreactors, plug-flow bioreactors, rotating-disc contactors, packed-bed fixed-biofilm reactors (or biofilters), fluidized bed reactors, diffused aeration tanks, airlift bioreactors, jet bioreactors, membrane bioreactors, and upflow bed reactors [28,30]. 

Himmelfarb et al. [80] introduced spin-filters as a cell retention device for high cell density perfusion cultivations of mammalian cells in suspension. Spin-filters are cylinders with a porous wall, which are placed inside stirred tank bioreactors, either mounted on the impeller shaft or driven by an independent motor (Fig. 5). Perfusate is pumped out from inside the spin-filter at the same... 

Several other processes were investigated and developed as well, e.g., a) Am-bruticin S production in airlift and stirred tank reactor b) high-cell density cultivation of E. coli and production of rDNA products c) production of thermostable xylanase by Thermomyces lanuginosus d) cultivation of Tetrahymena thermophila in 1.5 bioreactors, e) alginate production by Azotobacter vine-landii. 

Figure 11.9 Different arrangements and modes of operation for membrane bioreactors Continuous Stirred Tank Reactor (CSTR) with recirculation arrangement (a), dead-end cell (b), tubular with entrapped enzyme (c).

The bioreactor has been introduced in general terms in the previous section. In this section the basic bioreactor concepts, i.e., the batch, the fed-batch, the continuous-flow stirred-tank reactor (CSTR), the cascade of CSTRs and the plug-flow reactor, will be described. 

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