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Time constants for the process can provide relevant information for scale up. A comparison of the conversion time constant to the time constant for mixing allows determination of whether mixing will affect the process (Gommers et al., 1986; Schoutens et al., 1986a, 1986b, 1986c). If mixing is incomplete or the time constant for mixing is much larger than the time constant for conversion, conditions will differ at different heights in the reactor and biological stratification, which may or may not be desirable, may occur (Gommers et al., 1986).

Few other design examples exist in the literature. Schneeberg (1994) provides one in which a fluidized bed upgrade is added to an existing paper mill wastewater treatment plant. Badot et al. (1994) also gave a brief example of design for both a pilot scale and industrial scale reactor for various wastewater treatment applications. Andrews (1988) provided another example of aerobic wastewater treatment focusing on bioparticle optimization.

5.9Process Strategy

Before the details of a particular reactor are specified, the biochemical engineer must develop a process strategy that suits the biokinetic requirements of the particular organisms in use and that integrates the bioreactor into the entire process. Reactor costs, raw material costs, downstream processing requirements, and the need for auxiliary equipment will all influence the final process design. A complete discussion of this topic is beyond the scope of this chapter, but a few comments on reactor choice for particular bioprocesses is appropriate.

For those bioprocesses that follow Monod kinetics without substrate inhibition, a reactor configuration approaching plug flow behavior will give the highest rates of conversion. In three-phase fluidization, this means a high height to diameter ratio, within power consumption limits. The use of multiple stages is one possibility for overcoming the power consumption limitation on reactor height and would have additional benefits for bioprocesses in which separation of biomass growth and product generation is desirable (Fan, 1989).

If substrate inhibition exists, a well-mixed bioreactor is desirable. Mixing in three-phase fluidized bed bioreactors can be increased by adding an external recycle loop, by inserting a draft tube in the reactor, or by decreasing the height to diameter ratio.

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Conversely, product inhibition suggests the use of a reactor that emulates plug flow, as for the Monod kinetics without substrate inhibition discussed above. Alternatively, in situ product removal may alleviate product inhibition and improve productivity (Yabannavar and Wang, 1991). A bioparticle reactor for simultaneous fermentation/adsorption of fermentation or enzyme reaction products has been suggested and demonstrated by several workers (van der Wielen et al., 1990; Davison and Scott, 1992; Kaufman et al., 1995). Such a reactor makes use of the particle stratification observed in fluidized bed reactors, according to particle size and density. This allows a denser adsorbent particle to be added at the top of the reactor, from which it falls through the fluidized bed of biocatalysts, absorbing product as it passes. The dense beads are removed from the base of the bed and may be regenerated by product recovery for further use. By removing the product, which may inhibit the biological reactions taking place in the reactor, productivity is improved.

When mixed cultures are involved, the reaction kinetics may be complicated by interspecies relationships. For example, in the treatment of various waste waters, a Monod-type kinetics relating removal rate to organic loading rate has been verified (Converti et al., 1993). As expected, when the loading rate was increased or the residence time was decreased, either of which increase the substrate concentration, removal rate increased (Converti et al., 1993); however, this increased removal rate came at the cost of decreased removal efficiency. The initial biodegradative reaction (acidogenic) increased in rate faster than did the final reaction (methanogenic), resulting in a deleterious accumulation of organic acids. This had to be monitored and ameliorated through the addition of base to the reactor to protect the methanogenic stage (Converti et al., 1993).

For situations, such as the example above, where mixed cultures of degradative organisms have different optimal growth conditions, multiple stages would be desirable (Converti et al., 1993). This approach has been successfully demonstrated and, with the addition of a recycle stream from the second stage to the first, has been shown to have the additional costsaving benefit of reducing operating costs by decreasing the amount of caustic required for pH control, the major operational cost for full-scale anaerobic treatment plants (Romli et al., 1994). Another approach to multiple environmental optima for various species is the stratified bed suggested by Yang (1987), shown in Fig. 12. Use of support beads of various terminal velocities and a tapered bed can result in little or no axial

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which the bed is no longer fluidized. For the particulate and chain regimes, bed height has been shown to decrease as the field strength is increased. Gas holdup was affected by magnetic field strength, as well, increasing with increasing field strength (Hu and Wu, 1987), probably because magnetically stabilized particles had a greater tendency to break bubbles apart (Weng et al., 1992), and smaller bubbles have a slower rise velocity, resulting in greater gas holdup. Gas-liquid mass transfer was increased for the same reason (Weng et al., 1992). Radial distribution of gas and liquid flows tended to flatten with increased magnetic field (Hu and Wu, 1987; Weng et al., 1992).

Several applications of magnetically stabilized fluidized beds for bioprocessing have been demonstrated. Continuous cell suspension processing has been demonstrated in a magnetically stabilized fluidized bed that acted like a moving depth filter from which the solid matrix could be continuously removed to avoid clogging (Terranova and Burns, 1991); though this was demonstrated in a two-phase system, similar three-phase applications could be envisioned. Continuous ethanol fermentation has been performed in a three-phase magnetic fluidized bed (Weng et al., 1992). Production of caffeine and theobromine by plant cells in alginate magnetized with magnetite (Fe3O4) has also been demonstrated (Bramble et al., 1990). Other applications are likely to be demonstrated in the future.

Several improvements in the conventional airlift reactor have been suggested. Inverse fluidized bed bioreactors, based on airlift bioreactor principles and shown in Fig. 13, have been developed by several workers (Garnier et al., 1990; Nikolov and Karamanev, 1987, 1990). Low density, biofilm-covered particles are floated in the annular region of the airlift reactor; as the biofilm thickness increases, the particle density also increases and the particle bed expands downward. When the density is sufficiently high so that the particles reach the bottom of the bed, the particles are swept into the airlift sparged section in the reactor center where hydrodynamic forces strip some of the biofilm from the particles which then travel to the top of the reactor and return to the annular region. This cyclic mixing pattern has been shown to maintain a uniform biofilm thickness (Garnier et al., 1990). By adding a contained fluidized bed of coarser, denser particles in the airlift section, Nikolov and Karamanev (1987), improved attrition of biofilm from the particles. This reactor was superior to a conventional airlift reactor that used suspended cells for aerobic wastewater treatment by a mixed bacterial culture and for ferrous iron oxidation by Thiobacillus ferroxidans.

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A continuous centrifugal bioreactor, in which cells are fluidized in balance with centrifugal forces, has been designed to allow high density cell cultivation and superior aeration without elutriation of the suspended cells (van Wie et al., 1991). Reactor performance was hampered by elutriation of biomass by evolved gas in an anaerobic fermentation, indicating that it may not be suitable in its present state for three-phase fermentations. Immobilization of the cells on denser particles may overcome this problem.

In order to simultaneously achieve the advantages of plug flow operation (controlled residence time, reduced product inhibition) along with the advantages of intense mixing in each consecutive stage (good transport properties), the Blenke-Cascade reactor has been designed at the University of Hohenheim (Kottke et al., 1991). This reactor is a heavily baffled tower divided into many chambers by the baffles. Each chamber is well-mixed by fluidizing gas passing up the tower; the solid particles (biocatalysts) and liquid may flow coor countercurrently.

Several researchers have suggested contained fluidized bed for bioprocesses; such a reactor is depicted in Fig. 14. Kalogerakis and Behie (1995) have designed a three-phase/two region bioreactor for vaccine production. The bioparticles (microcarriers for animal cell culture) are contained in one region of the reactor and are kept in suspension by gentle mechanical agitation. An overall liquid flow is imposed on the whole reactor by the action of sparging in a separate central region, resulting in something of a hybrid of an airlift reactor and agitated reactor. Because the sparged section provides excellent aeration, the outer cell-containing region requires only mild agitation.

Naouri et al. (1991) described another contained fluidized bed, the so-called high compacting multiphasic reactor (HCMR), which they used for malic and lactic acid fermentations for wine improvement. Bioparticles were contained within a tapered region and liquid was rapidly recycled through this region by pumping; improved liquid/solid contact was cited as the advantage of this reactor.

Gas logging, the adherence of small bubbles to particles, causing them to rise to the surface in the reactor and form an inefficient packed bed with poor mass transfer properties, can be a problem in various fermentations and in wastewater treatment. A double entry fluidized bed reactor has been developed with simultaneous top (inverse) and bottom (conventional) inlets to overcome this problem (Gilson and Thomas, 1993).

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prevent product inhibition (Qureshi and Maddox, 1992). Another ABE fermentation scheme that included product removal by the inclusion of a fourth, extractive phase, showed outstanding improvements in process economics, reducing projected product costs by more than half (Busche and Allen, 1989); this improvement was not sufficient to beat the price for petrochemically derived butanol, but is an indication that as petroleum prices rise, three-phase biofluidization has a definite place in bioprocess design. These improvements in process economics are likely to be applicable to other fermentation processes.

For waste treatment rather than fermentation for product formation, again few examples of process economics exist in the literature. Those that do, favor fluidization. Badot et al. (1994) described an industrial prototype fluidized bed reactor that competed favorably on an economical basis with activated sludge processes for treating carbon pollution and was estimated to be economically comparable to fixed bed processes for denitrification. Schneeberg (1994) described the successful and economically-sound implementation of fluidization as an upgrade to an existing wastewater treatment plant. The restricted space available for extension of the wastewater plant made fluidization particularly advantageous in this case.

5.12 Summary

The complexity of the interaction of reactor hydrodynamics and performance with the biological metabolic processes is the major deterrent to widespread use of three-phase fluidization in biological processes. Most commercial applications of three-phase fluidization have thus far been in the area of wastewater treatment. Commercial fermentation and animal cell culture applications exist, but much of the work in this area remains at laboratory scale. In fermentation or cell culture systems, the solid phase is typically much lower in density than that found in traditional three-phase fluidized systems, and reactor hydrodynamics and transport properties can vary dramatically from those well-studied systems. As a greater understanding of reactor fundamentals for the new applications is obtained, more successful commercial applications of three-phase biofluidization for fermentations and cell culture are likely. Fortunately, the last few years have seen great strides in understanding the complex relationships of biofluidization, allowing increased confidence in design of large scale systems based on laboratory data.

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ACKNOWLEDGMENT

The authors would like to express their appreciation to researchers at BHP in Australia for providing information on the recent developments in smelting reduction of iron ore.

NOTATIONS

B= Ratio of buoyant density of the biofilm to the buoyant density of the support

Greek Symbols

ε= Void fraction

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σ= Stefan-Boltzmann constant

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