Scaling Up Stirred Tanks

This section is concerned with the UA xtiT — Text) term in the energy balance for a stirred tank. The usual and simplest case is heat transfer from a jacket. Then A xt refers to the inside surface area of the tank that is jacketed on the outside and in contact with the fluid on the inside. The temperature difference, T - Text, is between the bulk fluid in the tank and the heat transfer medium in the jacket. The overall heat transfer coefficient includes the usual contributions from wall resistance and jacket-side coefficient, but the inside coefficient is normally limiting. A correlation applicable to turbine, paddle, and propeller agitators is 

Assuming geometric similarity and recalling that Dj scales as gives 

For a scaleup with constant power per unit volume, Example 4.7 showed that Ni 

If we want UA xtiT — Text) to scale as S, the driving force for heat transfer must be increased  

These results are summarized in the last four rows of Table 4.1. Scaling the volume by a factor of 512 causes a large loss in hAg t per unit volume. An increase in the temperature driving force (e.g., by reducing by a factor of 10 could compensate, but such a large increase is unlikely to be possible. Also, with cooling at the walls, the viscosity correction term in Equation (5.34) will become important and will decrease hAg t still more. 

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The most common problem in scaling up stirred tank reactors is the difficulty in maintaining the desired operating temperature. The current section assumes this is possible. Techniques for maintaining a desired energy balance are deferred to Chapter 5. 

Hempel, D. C., and H. Dziallas (1999). Scale-up, stirred tank reactors, in Encyclopaedia of Bioprocess Technology Fermentation, Biocatalysis and Bioseparation, Vol. 3, M. C. Flickinger and S. W. Drew, eds., Wiley, New York, pp. 2314-2332. 

Over 25 years ago the coking factor of the radiant coil was empirically correlated to operating conditions (48). It has been assumed that the mass transfer of coke precursors from the bulk of the gas to the walls was controlling the rate of deposition (39). Kinetic models (24,49,50) were developed based on the chemical reaction at the wall as a controlling step. Bench-scale data (51—53) appear to indicate that a chemical reaction controls. However, flow regimes of bench-scale reactors are so different from the commercial furnaces that scale-up of bench-scale results caimot be confidently appHed to commercial furnaces. For example. Figure 3 shows the coke deposited on a controlled cylindrical specimen in a continuous stirred tank reactor (CSTR) and the rate of coke deposition. The deposition rate decreases with time and attains a pseudo steady value. Though this is achieved in a matter of rninutes in bench-scale reactors, it takes a few days in a commercial furnace. 

This chapter treats the effects of temperature on the three types of ideal reactors batch, piston flow, and continuous-flow stirred tank. Three major questions in reactor design are addressed. What is the optimal temperature for a reaction How can this temperature be achieved or at least approximated in practice How can results from the laboratory or pilot plant be scaled up ... 

The main disadvantage of all these systems is the Hmitation of scale-up. Monoclonal antibodies are produced by multiplying the hollow fiber systems and stirred tank reactors with membrane aeration are known up to 100 liter. Small quantities of product can be produced by these systems but they are not suitable for real industrial scale-up. 

To illustrate the complexity of process optimization, suppose that we are to scale-up a semibatch stirred-tank reactor for carrying out the following consecutive reactions ... 

Factors re.sponsible for the occurrence of scale-up effects can be either material factors or size/shape factors. In addition, differences in the mode of operation (batch or semibatch reactor in the laboratory and continuous reactor on the full scale), or the type of equipment (e.g. stirred-tank reactor in the laboratory and packed- or plate- column reactor in commercial unit) can be causes of unexpected scale-up effects. A simple misuse of available tools and information also can lead to wrong effects. 

An example Hollander et al. (2001a) nicely demonstrated how the strong inhomogeneities in stirred-tank flow result in unpredictable scale-up behaviour and that the impact of the detailed hydrodynamics and of the non-uniform spatial particle distribution on agglomeration rate is larger and more complex than usually assumed their study once more illustrated the risks of scale-up on the basis of keeping a single non-dimensional number. Sophisticated CFD, especially on the basis of LES, offers an attractive alternative indeed. 

Stirred tank reactors are mostly used because they provide a rapid means of obtaining a uniform composition and temperature throughout the reaction mixture they also offer the flexibility required for the small-scale production of many different molecules. Companies such as Biazzi, Davy Process Technology (Buss loop technology), DeDietrich and others provide technology adapted to hydrogenations (i.e., pressures up to 100 bar and temperatures up to 200 °C) [45-47]. Here, some scale-up issues related to stirred tank reactors are described. 

Table 3.5 shows that the study of chemical kinetics is critical in successful scale-up of catalytic systems, of gas-phase controlled systems, and of continuous tank stirred reactors (CSTR). For scale-up of batch systems consisting of gas or liquid compounds, chemical kinetics and heat transfer effects must be studied because the combination of these phenomenon determine the conditions for a runaway and thus involve the safety of the operation. 

Choudhury, S., and L. Utiger, "Warmetransport in Ruhrkesseln Scale-up Methoden" ("Heat Transfer in Stirred Tanks Scale-up Methods"), Chem. Ing. Tech., 62,154-155 (1990). 

Scale-up considerations for batch flocculation in stirred tanks indicate that similar results are obtained with ... 

Optimal fermentation parameters have been well established and air-lift, stirred tank, and hollow fibre systems have all been used. At commercial scale, fermentation volumes in excess of 1000 litres can be used, which can yield 100 g or more of final product. While hybridoma growth is straightforward, production levels of antibody can be quite low compared with ascites-based production systems. Typically, fermentation yields antibody concentrations of 0.1-0.5 mg/ml. Removal of cells from the antibody-containing media is achieved by centrifugation or filtration. An ultrafiltration step is then normally undertaken in order to concentrate the filtrate by up to 20-fold. 

Laboratory studies of the rearrangement process began with semi-continuous operation in a single, 200-mL, glass reactor, feeding 1 as a liquid and simultaneous distillation of 2,5-DHF, crotonaldehyde and unreacted 1. Catalyst recovery was performed as needed in a separatory funnel with n-octane as the extraction solvent. Further laboratory development was performed with one or more 1000-mL continuous reactors in series and catalyst recovery used a laboratory-scale, reciprocating-plate, counter-current, continuous extractor (Karr extractor). Final scale-up was to a semiworks plant (capacity ca. 4500 kg/day) using three, stainless steel, continuous stirred tank reactors (CSTR). 

Pertinent examples of the value of dimensional analysis have been reported in a series of papers by Maa and Hsu (19,37,63). In their first report, they successfully established the scale-up requirements for microspheres produced by an emulsification process in continuously stirred tank reactors (CSTRs) (63). Their initial assumption was that the diameter of the microspheres, <7ms, is a function of phase quantities, physical properties of the dispersion and dispersed phases, and processing equipment parameters ... 

Houcine I, Plasari E, David R, Villermaux J. Feedstream jet intermittency phenomenon in a continuous stirred tank reactor. Chem Eng J 1999 72 19-29. Zlokarnik M. Dimensional analysis and scale-up in theory and industrial application. In Levin M, ed. Process Scale-Up in the Pharmaceutical Industry. New York Marcel Dekker, 2001. 

It would not be possible to adequately cover the field of stirred tank scale-up in the space available here. Instead, this section will touch briefiy on the important issues in bioreactor scale-up. For more detailed methodologies on stirred tank bioreactor scale-up, the reader is referred to several review papers on the topic (30,37,38). 

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