Bioreactor stirred

Doran, P.M. (2010) Bioreactors, stirred taidc for culture of plant cells, in Encyclopedia of Industrial Biotechnology Bioprocess, Bioseparation, and Cell Technology (ed. M.C. Flickinger),... 

Manipulation of oxygen concentration and fluid shear stress within PSC differentiation cultures is possible by employing controlled, stirred suspension bioreactors. Stirred suspension cultures (SSC) are well suited to control many aspects of the cellular environment. Stirring prevents formation of spatial concentration gradients within the bulk media, thus a point measurement reflects the conditions that all cells are exposed to. The ability to accurately measure culture conditions, such as oxygen tension or pH, allows control processes to maintain constant conditions or to change conditions as desired over time. SSC are also a practical means for scale-up, as vessel volume can be increased provided shear forces or sparging do not deleteriously affect the cells (van der Pol and Tramper 1998). 

In a stirred bioreactor the Hquid is generally considered weU-mixed, ie, is spatially constant. The gas phase too may be weU-mixed (19) so that... 

The specific surface, a, is also relatively insensitive to the duid dynamics, especially in low viscosity broths. On the other hand, it is quite sensitive to the composition of the duid, especially to the presence of substances which inhibit coalescence. In the presence of coalescence inhibitors, the Sauter mean bubble size, is significantly smaller (24), and, especially in stirred bioreactors, bubbles very easily circulate with the broth. This leads to a large hold-up, ie, increased volume fraction of gas phase, 8. Sp, and a are all related... 

Eigure 6 enables a comparison to be made of kj a values in stirred bioreactors and bubble columns (51). It can be seen that bubble columns are at least as energy-efficient as stirred bioreactors in coalescing systems and considerably more so when coalescence is repressed at low specific power inputs (gas velocities). 

Fig. 6. A comparison of k a values (51). Represented are 1, stirred bioreactor using water, = 0.02 m/s, kj a (eq. 16) 2, stirred bioreactor using water, t 3 = 0.04 m/s, kj a (eq. 16) 3, bubble column using water, kj a (eq. 18) 4, stirred bioreactor using salt water, = 0.02 m/s, kj a (eq. 17) 5, stirred bioreactor using salt water, = 0.04 m/s, kj a (eq. 17) and 6, bubble column using salt water (noncoalescing).

Plant Cell Culture. Air-lift bioreactors have been favored for plant cell systems since these cultures were first studied (4). However, they can give rise to problems resulting from flotation of the cells to form a meringue on the top. It is interesting to note that some reports indicate that stirred bioreactors do not damage such cells (4). 

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. 

Two types of bioreactors have been used to produce SCP from sugar sources, namely stirred/baffled type and the air-lift with draught tube type (figure 4-5), with various capacities up to 400 m. 

Compared to a conventional stirred bioreactor, an air-lift pressure-cycle bioreactor is more suitable for development of a SCP process from methanol because ... 

True. Stirred bioreactors require finely engineered aseptic seals on shaft bearings,... 

False. The behaviour of stirred bioreactors does not resemble closely pressure-cycle fermentors at any scale. 

Conventional stirred reactors with working volumes of 50 to 150 m3 have been used routinely for citric add production whereas tower bioreactors, currently 200 m and larger (greater than 600 m3) are envisaged. 

The submerged culture process continues to increase in terms of the percentage of dtric acid produced compared to that produced by the surface culture method. Tower bioreactors are preferred over stirred reactors because they cost less, there is less risk of contamination and they are less limited by size. 

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.

Non-stirred, non-aerated system about 70% of bioreactors are in this category. 

Non-stirred, aerated vessels are used in the process for traditional products such as wine, beer and cheese production. Most of the newly found bioprocesses require microbial growth in an aerated and agitated system. The percentage distribution of aerated and stirred vessels for bioreactor applications is shown in Table 6.1. The performances of various bioreactor systems are compared in Table 6.2. Since these processes are kinetically controlled, transport phenomena are of minor importance. 

TABLE 6.1. Percentage of distribution aerated and stirred vessel in bioreactor application... 

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]). 

As is the case with pure bubble columns and gas-operated loop reactors, most bioreactors in technical use are aerated with oxygen or air. Reactors with pure surface aeration, such as roller bottles, shake flasks and small stirred reactors or special reactors with membrane aeration, are exceptions. The latter are used for the cultivation of cells and organisms which are particularly sensitive to shearing (see e. g. [28 - 29]). The influence of gas bubbles in increasing stress has been described in many publications (see e.g. [4, 27, 29, 30]). In principle it can be caused by the following processes ... 

Fig. 23. Average particle size dp after t = 120 h stirring for various impeller types and working conditions (left hand diagram data from [60]) and correlation with the maximum energy dissipation 8 (right hand diagram) stirred bioreactor with 4 baffles V = 6L D = 0.2m H/D = 0.96 zi=l...

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