Biotechnol. zyxwvutsr Prog. zyxwvu 1992, 8, 19-24 19 zyxwvutsrqp Optimal Design of the Tubular Microporous Membrane Aerator for Shear-Sensitive Cell Cultures W. Winston SU,~ Hugo S. Caram, and Arthur E. Humphrey* zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLK BioProcessing Institute, Department of Chemical Engineering, Lehigh University, Bethelehem, Pennsylvania 18015 In this paper, a theoretical analysis of oxygen transport across the tubular microporous membrane is described. This analysis has provided some insight into the optimal design of the membrane aerator. It was found in this study, at fixed inlet pressure, that the overall membrane oxygen transfer rate increases with increased tubing length only up to a certain length, i.e., the “critical length”. When a large membrane surface area is required, the fiber should be divided into parallel segments to increase the overall oxygen transfer rate. A manifold or a gas distributor can then be used to distribute gas into segments of tubing. The length of each segment cannot exceed the critical length. In addition, shorter tube segments should give a higher oxygen transfer rate per unit tube length; however, this advantage is counterbalanced by the fact that gas distribution into huge numbers of parallel tubings may not be uniform. Introduction Bubble-free aeration using immersed membranes in cell culture has been proposed for more than a decade. Such systems are commonly used in blood oxygenation units. Membrane aeration systems sustain high mass transfer capabilities under high culture viscosity due to the fact that they have a constant gadliquid interfacial area. This is a very desirable feature for aerating plant cell cultures since plant cell cultures can be very viscous at high cell densities. Membrane aeration can also eliminate foaming, cell flotation, and therefore the undesirable wall growth and culture deterioration. In addition, hydrodynamic shear damage due to bubble breakup, which is believed to be the major contributor to the hydrodynamic force related cell death under mild agitation in sparged, mechanically agitated reactors (Yang and Wang, 19911, can be avoided when membrane aeration is used. Thin-walled silicone membrane tubing has been used to provide bubble-free oxygenation in small-scale insect and animal cell cultures (Kilburn and Morley, 1972;Eber- hard and Schugerl, 1987). Commercial bioreactors have been constructed using the siliconetubing to supply oxygen and to remove COS,e.g., Invitron’s maintenance reactor and B. Braun’s Biostate MC fermenter (Figure 1). Another well-known application of silicone membrane aeration is the blood oxygenator used in artificial heart/lung devices, in either flat-plate-and-sheet or spiral-coil geometry. Siliconemembrane has higher oxygen permeability than most of the dense polymeric membranes. However, the diffusion barrier associated with silicone membrane is still quite significant. On the other hand, a low value of inherent mass transfer resistance (diffusion barrier) for microporous polypropylene membranes has been dem- onstrated in our laboratory, compared to the thin-walled silicone tubing operating at similar conditions (Su, 1991). One will benefit from the low inherent mass transfer resistance of the microporous membrane, especially in large-scale fermenters, where the impeller Reynolds num- zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA * Corresponding author. + Current address: Department of Agricultural Engineering, University of Hawaii, Honolulu, HI 96822. zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Insert Holder oncave Bottom Figure 1. Schematic of B. Braun’s Biostate MC reactor. Reprinted with permission from the product information MC- 0986-E. Copyright B. Braun Biotech Inc., Allentown, PA. ber increases with the reactor volume if the fermenter scale-up is based on constant power input (Su, 1991). As a result, an increase in the reactor volume should decrease the liquid fii resistance. In large fermenters, the inherent resistance may become the major contributor to the overall mass transfer resistance. Moreover, the microporous polymer membrane shows better mechanical strength than the thin-walled silicone membrane. As for the stagnant liquid film mass transfer resistance associated with the tubular aeration membrane, it can be reduced by using a radial-flow paddle impeller (Su, 1991). One restriction in using the microporous membrane, however, is its low bubble point (theoperating gas pressure inside the tubular membrane, beyond which bubbles will form on the outer surface of the porous membrane). This limits the operating pressure inside the membrane tube. The use of hydrophobic microporous membrane fibers for culture aeration was first proposed by Lehmann (Leh- mann et al., 1985)for aerating cell cultures. In his studies, the membrane tubing was coiled on a carrier that was 8756-7938/92/3008-0019$03.00/0 0 1992 American Chemical Society and American Institute of Chemical Engineers