Alginate‐Polylysine Microcapsules of Controlled Membrane Molecular Weight Cutoff for Mammalian Cell Culture Engineering

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Abstract
The search for more productive mammalian cell culture techniques has been primarily driven by the need to increase both the cell density and product concentration. In the technique used in our laboratory, microencapsulation, hybridoma cells were grown and monoclonal antibody was entrapped within microcapsules, which had a controlled membrane molecular weight cutoff. In our studies it was shown that using the alginate‐poly‐l‐lysine (PLL) microcapsule system and protein diffusion experiments, the capsule membrane molecular weight cutoff could be controlled from 20 × 103 to 300 × 103. This was achieved by increasing the viscosity average molecular weight (Mv) of the LL, used in the encapsulation procedure, from 14 × 103 to 525 × 103 and by decreasing the alginate — PLL reaction time from 40 minutes to 6 minutes. Cell culture studies with microencapsulated mouse hybridoma cells indicated that while the conventional (single‐membrane) microcapsules produced a maximum intracapsular cell density of about 2 × 107 cells/mL and a monoclonal antibody concentration of 1250 μg/mL, a modified (multiple‐membrane) capsule resulted in intracapsular cell densities of about 6 × 107 cells/mL and monoclonal antibody concentrations of 5300 μg/mL. These significant improvements in cell density and monoclonal antibody concentration were attributed to a lower (22%) intracapsular alginate content as well as better retention of the cell product by the modified capsule membrane.