Bioreactors fermentor

We will now deal with quite sophisticated issues concerning reactor design and performance. Although we deal with these in a sympathetic manner, you may find it useful to refresh your knowledge by reading more about bioreactors. The BIOTOL series offers opportunities to learn more about fermentors. 

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

As well as understanding and optimising the working efficiency of the bioreactor it was also vital to optimise the efficiency of the fermentor - the micro-organism itself. The biochemistry of methanol utilisation is similar to that of methantrophs described in Section 4.9.2, and is shown in Figure 4.9. 

PLATE 4 Bioreactors that use mammalian cells, like this tower fermentor, are on the cutting edge of new biotechnology manufacturing processes. Courtesy, Cetus Corporation. 

The 1980 s and the early 1990 s have seen the blossoming development of the biotechnology field. Three-phase fluidized bed bioreactors have become an essential element in the commercialization of processes to yield products and treat wastewater via biological mechanisms. Fluidized bed bioreactors have been applied in the areas of wastewater treatment, discussed previously, fermentation, and cell culture. The large scale application of three-phase fluidized bed or slurry bubble column fermen-tors are represented by ethanol production in a 10,000 liter fermentor (Samejima et al., 1984), penicillin production in a 200 liter fermentor (Endo et al., 1986), and the production of monoclonal antibodies in a 1,000 liter slurry bubble column bioreactor (Birch et al., 1985). Fan (1989) provides a complete review of biological applications of three-phase fluidized beds up to 1989. Part II of this chapter covers the recent developments in three-phase fluidized bed bioreactor technology. 

Tragardh, Ch., A Hydrodynamic Model for the Simulation of an Aerated Agitated Fed-Batch Fermentor . Proceedings of the 2nd International Conference on Bioreactor Fluid Dynamics, Cambridge, UK 117-134 (1988). 

This bioreactor mode refers to a tank fermenter operated semi-continuously. The rate of the feed flow, F0, may be variable, and there is no outlet flow rate from the fermentor. As a consequence of feeding the reactor volume will change with respect to time. 

M potassium phosphate buffer pH 8.0 (1000 mL) hydrochloric acid (cone.) (100 mL) distilled water (1000 mL) fermentor/ bioreactor (1.5 L capacity) rotary vacuum evaporator/oven ice... 

Commercial manufacturing operations in biotechnology usually employ bioreactors or fermentors for product expression. In this discussion, the term fermentor will refer to bacterial or fungal processes and the term bioreactor to animal cell cultures. While extensive description of the operation... 

Bioreactors are the apparatus in which practical biochemical reactions are performed, often with the use of enzymes and/or living cells. Bioreactors that use living cells are usually called fermentors, and specific aspects of these are discussed in Chapter 12. Ihe apparatus applied to waste water treatment using biochemical reactions is another example of a bioreactor. Even blood oxygenators, that is, artificial lungs as discussed in Chapter 15, can also be regarded as bioreactors. 

As most biochemical reactions occur in the liquid phase, bioreactors usually handle liquids. Processes in bioreactors often also involve a gas phase, as in cases of aerobic fermentors. Some bioreactors must handle particles, such as immobilized enzymes or cells, either suspended or fixed in a liquid phase. With regard to mass transfer, microbial or biological cells may be regarded as minute particles. 

Stirred (agitated) tanks, which are widely used as bioreactors (especially as fermentors), are vertical cylindrical vessels equipped with a mechanical stirrer (agitator) or stirrers that rotate around the axis of the tank. 

Bioreactors that use enzymes but not microbial cells could be regarded as fermentors in the broadest sense. Although their modes of operation are similar to those of microbial fermentors, fed-batch operation is seldom practiced for enzyme reactors. The basic equations for batch and continuous reactors for... 

Temperature Ihe temperature in a bioreactor is an important parameter in any bioprocess, because all microorganisms and enzymes have an optimal temperature at which they function most efficiently. For example, optimal temperature for cell growth is 37 °C for Escherichia coli and 30 °C for Saccharomyces sp, respectively. Although there are many types of devices for temperature measurements, metal-resistance thermometers or thermistor thermometers are used most often for bioprocess instrumentation. The data of temperature is sufficiently reliable and mainly used for the temperature control of bioreactors and for the estimation of the heat generation in a large-scale aerobic fermentor such as in yeast production or in industrial beer fermentation. 

Suppose the objective is to control the temperature of a bioreactor. The temperature of a bioreactor is measured by instrumentation and compared with a set-point value. Based on the difference between the measured and the set-point temperature, the flow rate of cooling water into a fermentor jacket is increased or decreased by manipulating a control valve of cooling water until the difference between the measured and the set-point temperature becomes zero. By repeating this operation, the temperature of a bioreactor can be kept constant regardless of changes in the outer temperature or from the internal generation of heat. 

Batch cultivation is perhaps the simplest way to operate a fermentor or bioreactor. It is easy to scale up, easy to operate, quick to turn around, and reliable for scale-up. Batch sizes of 15,000 L have been reported for animal cell cultivation [2], and vessels of over 100,000 L for fermentation are also available. Continuous processes can be classified into cell retention and non-cell retention. The devices typically used for cell retention are spin filters, hollow fibers, and decanters. Large-scale operation of continuous processes can reach up to 2,000 L of bioreactor volume. Typically, the process is operated at 1-2 bioreactor volumes... 

Commercial fermentations are conducted in large bioreactors which are usually referred to as fermentors and arc designed tor operation in batch, fed-baldi. or continuous ferine illation modes. The batch and fed-batch procedures are used for most commercial antibiotic fermentations. 

Bioseparation practitioners can probably benefit from the control experience of bioreactor operation. Several extensive articles on the instrumentation of bioreactors discuss issues and approaches to measuring temperature, pressure, flow, and volume pH, dissolved oxygen and C02, redox potentials, and specific ions or chemicals.9 11 Control of bioreactors has been a fertile research area for a number of years, particularly with respect to fermentor control.12... 

A key problem in bioreactor control is the difficulty in obtaining reliable sensors and consequently of reliable on-line process information. Demands for product consistency and process productivity produce requirements for more process information.13 Especially in the case of fermentors, rapid, accurate on-line measurement of process variables is often a complex task. As a result, much research effort has focused on methods for quantitatively estimating compositions within reactors and on using model-based control techniques. 

The present state of development in biosensors is at a level where the sensor is used outside the bioreactor. This step has been taken because of sterility problems with the bioreactor and stability problems concerning the biosensor. As long as no sterilizable biosensor is available, most of the applications must be performed outside the fermentor. In such cases, leakage will cause no practical problems, except that more enzyme may be needed. 

Once the expression of the protein is optimized and seed stocks are made, the next step in production is their growth on a large scale to generate sufficient product. The scale of fermentation is determined by the therapeutic dose of the product, the total number of doses required, and the shelf-life of the product. The ideal characteristics of a bioreactor or a fermentor are listed in Table 3.3. 

An example of this configuration is filtration of the methane fermentation broth from a sewage sludge liquor [Kayawake et al., 1991]. The liquor is u eated anaerobically in a fermentor. The broth is pumped to a ceramic membrane module which is contained in the fermentor. The retentate is returned to the fermentor while the permeate is discharged to the environment This is schematically shown in Figure 8.2. Although the membrane module is enclosed in the bioreactor for compactness and process simplification, the membrane step in essence follows the fermentation step. 

---