Design, characterization and application of the multiple air-lift loop bioreactor

A new bioreactor is introduced: the Multiple Air-lift Loop reactor (MAL). The MAL consists of a series of air-lift loop reactors within one vessel. With the MAL, a new type of geometry for air-lift reactors with an internal loop is introduced. This new geometry was characterized with respect to hydrodynamics, mixing and oxygen transfer. The hydrodynamics were described by an existing model. Hydrodynamics, mixing and oxygen transfer in the new reactor configuration were comparable to that in conventional air-lifts with an internal loop.

The design and use of the MAL as a reactor cascade, to approximate plug-flow behaviour, were studied. Biological model systems were used to compare the reactor series to a single vessel. These model systems included immobilized invertase and nitrifying bacteria. With the immobilized invertase it was shown that a threecompartment MAL gives an improved substrate conversion when compared to a single vessel of the same overall volume. This could be described with a previously developed model. Also for the immobilized nitrifying bacteria improved substrate conversion was shown in the comparison between a series and a single vessel. Free suspended hybridomas were used for monoclonal antibody (MAb) production. It was shown that reactor series can be useful research tools for kinetic studies. In the second vessel in the series conditions were obtained that can hardly be reached in a single vessel. Not only growth, but also death could be studied under stable conditions. A model was derived that describes hybridoma growth and their MAb production.

Vessels in a series can be of equal volume, but very often unequal volumes can be more advantageous. Therefore, choosing the appropriate reactor volumes is an important design step, which is discussed for different applications. Finally, a general procedure for choosing the optimal bioreactor cascade configuration for any application is given.