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Bioreactor volume (m )

Fig. 9.7. Effect of scale on the ability to remove the waste metabolic heat by wall cooling in a continuously-mixed, forcefully-aerated bioreactor, of the type shown in Fig. 9.3(a), as calculated by Nagel et al. (2001a). The Y-axis represents the ratio of the maximum wall cooling capacity to the maximum metabolic heat production rate. The calculations are done for three length-to-diameter ratios in a situation in which the maximum O2 uptake rate is 0.0191 mol s-1 m-3 bed, the overall heat transfer coefficient for heat transfer across the wall to the cooling water is 100 W m-2 °C-1 and the temperature difference between the wall and the bed is 20°C. Where the curve is above the dashed horizontal line, wall cooling is sufficient to maintain the bed temperature at the desired value. Conversely, where the curve is below the dashed horizontal line wall cooling is not sufficient to maintain the bed temperature. Adapted from Nagel et al. (2001a) with kind permission from John Wiley & Sons, Inc.

Pressure drop has been little studied in continuously-mixed, forcefully-aerated bioreactors. It would not be expected to be a problem, since the mixing action should squash hyphae onto the particle surface, preventing them from growing into the inter-particle spaces. Likewise, the appearance of cracks in the bed should not be a problem since the particles will not be bound together. However, preferential flow could occur due to differences in the bed height caused by:

• the mixing action. For example, in the conical bioreactor shown in Fig. 9.2(b), the rotation of the helical mixing blade causes the sides of the bed to be higher than the middle, as indicated by the vertical section of the bed shown in Fig. 9.8(b). Air will flow preferentially through the center of the bed.

• the design of the bioreactor itself. For example, in the bioreactor shown in Fig. 9.3(d), the curvature of the base of the bioreactor means that the bed height varies as a function of position, even if the top of the bed is horizontal. In this case air will flow preferentially through the sides where the bed is thinnest.

Fig. 9.8. Representation of the type of information that positron emission particle tracking studies can provide, which was demonstrated with a conical solids mixer adapted for use as a bioreactor (Schutyser et al. 2003b). As shown in Fig. 9.2(b), the bioreactor contains a spiral mixing blade that follows the inside of the wall and rotates counterclockwise, although this detail is not shown here for the sake of clarity. (a) The principle of positron emission particle tracking. The particle contains a radioactive isotope that emits positrons. Emitted positrons immediately annihilate with electrons and two 0.51 MeV gamma rays leave the annihilation site in diametrically opposed directions. These gamma rays are registered by detectors that are placed around the bioreactor. The position of the particle at any particular instant can be determined simply by finding the intersection of the "annihilation vectors" resulting from the various positrons emitted at that instant; (b) The data can be analyzed to give particle velocity vectors within any plane. In this particular case, the velocity vectors are shown in a vertical plane that passes through the central axis of the bioreactor. The longer the arrow the greater the velocity; (c) The trajectory of individual particles can be plotted. Shown here are smoothed trajectories of two particles, in side and overhead views. Key: (—) A particle being pushed up the wall of the bioreactor by the mixing blade;

(---) A particle descending in the middle of the bioreactor. Adapted from Schutyser et al.

(2003b) with kind permission from John Wiley & Sons, Inc.

In addition, the agitator may cause transient open channels as it mixes the bed. In other words, as the agitator moves, it may leave a gap behind it. Even though the solid bed may later collapse to fill the gap, air will flow preferentially through the gap while it is open.

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