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Cell Culture Bioreactor: Bubble Free Gas Control

Bioreactor Gas Exchange: Bioreactor gas control using PermSelect gas exchangersBioreactor Gas Exchange: Bioreactor gas control using PermSelect gas exchangers

Successful cell culture requires effective management of metabolic gases within the media. As cell densities increase, the gas conditioning requirements go up dramatically. Rather than subject cells to higher shear stress by paddle systems, foaming due to sparging, or deal with increasingly large headspace requirements to condition the media, MedArray's silicone hollow fiber membrane modules can regulate gas levels to achieve the desired productivity. Our membrane modules use silicone hollow fibers which are dense, without pores, and thus not susceptible to fouling or pore wet-out. Since the gas transfer occurs via diffusion through the membrane, it does not produce bubbles and as a result, eliminates foaming and turbulence within the culture vessel. The membrane modules can be steam sterilized, gas sterilized, autoclaved, and gamma irradiated. Additionally, silicone is inert and well characterized in bio-applications.

How do I control dissolved gases in a cell culture bioreactor using a PermSelect® membrane module?

Using a PermSelect® silicone membrane module to control dissolved gases in your cell culture media is simple. There are many options depending on your specific application but the most straightforward configuration is illustrated below. A media stream is continuously drawn from a selected location in the bioreactor vessel and driven with a pump through the shell side of the PermSelect® membrane module. A gas (such as oxygen) or mixture of gases is flown through the lumen side of the membrane module to equilibrate the dissolved gases in the media to this gas composition. The conditioned media exiting the membrane module is returned to the biorecator vessel, thereby maintaining a desired bioreactor dissolved gas composition in the media. To remove gases from your bioreactor (such as excessive CO2 or other toxic gases) a vacuum may be applied to the lumen side of the module instead.

PermSelect® membrane modules can replace any membrane oxygenator such as spiral wound silicone oxygenators (ECMO oxygenators) in cell culture bioreactor applications.

Bioreactor Gas Control using a Silicone Membrane Module: Bioreactor Gas Control using a Silicone Membrane ModuleBioreactor Gas Control using a PermSelect® Silicone Membrane Module

Silicone (PDMS) membranes have been used and demonstrated to provide adequate oxygen supply to high density cell cultures and to aid in stirred tank bioreactors. The following published articles describe the effective use silicone membranes for this purpose.

  • A comparison of mass transfer coefficients between trickle-bed, hollow fiber membrane and stirred tank reactors
    Bioresource Technology Volume 133, April 2013, Pages 340–346
    J.J. Orgill, et al.

    Trickle-bed reactor (TBR), hollow fiber membrane reactor (HFR) and stirred tank reactor (STR) can be used in fermentation of sparingly soluble gasses such as CO and H2 to produce biofuels and bio-based chemicals. Gas fermenting reactors must provide high mass transfer capabilities that match the kinetic requirements of the microorganisms used. The present study compared the volumetric mass transfer coefficient (KtotA/VL) of three reactor types; the TBR with 3 mm and 6 mm beads, five different modules of HFRs, and the STR. The analysis was performed using O2 as the gaseous mass transfer agent. The non-porous polydimethylsiloxane (PDMS) HFR provided the highest KtotA/VL (1062 h−1), followed by the TBR with 6 mm beads (421 h−1), and then the STR (114 h−1). The mass transfer characteristics in each reactor were affected by agitation speed, and gas and liquid flow rates. Furthermore, issues regarding the comparison of mass transfer coefficients are discussed.

  • Oxygenation of intensive cell-culture system
    Applied Microbiology and Biotechnology Volume 43, Number 6, 1028-1033
    A. N. Emery, et al.

    The abilities of various methods of oxygenation to meet the demands of high-cell-density culture were investigated using a spin filter perfusion system in a bench-top bioreactor. Oxygen demand at high cell density could not be met by sparging with air inside a spin filter (oxygen transfer values in this condition were comparable with those for surface aeration). Sparging with air outside a spin filter gave adequate oxygen transfer for the support of cell concentrations above 107 ml–1 in fully aerobic conditions but the addition of antifoam to control foaming caused blockage of the spinfilter mesh. Bubble-free aeration through immersed silicone tubing with pure oxygen gave similar oxygen transfer rates to that of sparging with air but without the problems of bubble damage and fouling of the spin filter. A supra-optimal level of dissolved oxygen (478% air saturation) inhibited cell growth. However, cells could recover from this stress and reach high density after reduction of the dissolved oxygen level to 50% air saturation.

Contact an applications engineer, or call +1 (734) 769-1066 to discuss your particular cell culture bioreactor gas control needs. MedArray provides its PermSelect® membrane modules to researchers, and to industry through original equipment manufacturers (OEM’s) who are interested in integrating gas control solutions in their cell culture bioreactors. We can also customize membrane modules to your specific application. Contact us to discuss your custom application.