HYDRODYNAMIC BEHAVIOR OF ANIMAL-CELL MICROCARRIER SUSPENSIONS IN SPLIT-CYLINDER AIRLIFT BIOREACTORS

Hydrodynamic characteristics of suspensions of microcarriers used for culturing anchorage dependent animal cells are reported in split-cylinder internal-loop airlift bioreactors. Cell culture media are simulated using salt solutions that duplicate the ionic strengths of typical media. Effects of solids loading (0-30 kg . m(-3)), microcarrier particle size (150-300 x 10(-6) m diameter) and density (1030-1050 kg . m(-3)) on gas induced circulation of the slurry, mixing time, gas holdup and gas velocity requirements to attain complete suspension of solids are discussed for two reactors with aspect ratios of 7.6 and 14.5, but equal riser-to-downcomer cross-sectional area ratios of 1.0, aerated at low air flow rates (0-8 x 10(-6) m(3) . s(-1)) through a sintered glass sparger with 110 x 10(-6) m diameter pores. The study covers the ranges of solids concentrations, types, densities, particle sizes and aeration rates that are of relevance in animal cell culture applications. Airlift bioreactors displayed suitable hydrodynamic characteristics for potentially supporting anchorage dependent cell cultures on microcarriers at carrier loadings similar to those that are currently used in stirred tank bioreactors. The minimum gas flow rates and the induced liquid circulation rates necessary to achieve and maintain suspension of the heaviest and the largest microcarriers were well within practicable limits, limits which have been shown to be withstood by animal cells in non-anchorage dependent suspension culture in airlift bioreactors. No floatation problems were encountered with the carriers, nor was sedimentation a problem so long as the identified minimum suspension criteria were met. Chisti's liquid circulation equation, originally intended for two-phase flow, applied to the three-phase gas-liquid-microcarrier systems.