Hydrodynamics of a liquid-liquid-solid fluidized-bed bioreactor

If a batchwise bioconversion and subsequent ( <em>i.e.</em> serial) downstream processing are adopted as a standard production strategy, a low overall productivity may result for certain types of biotransformations (substrate- or product-inhibited fermentations). An alternative to sequential processing would be the integration of bioconversion and downstream processing by controlled supply of substrate to the reaction <em>in situ</em> , or by controlled removal of product from the reaction <em>in situ</em> . Such integration involves a multi-phase reactor in which a helper phase may serve as substrate reservoir or as product sink. A new type of multi-phase bioreactor was developed, containing a continuous liquid phase, a dispersed liquid phase, and a dispersed solid phase; it may be conceived of as a 3-phase liquid-liquid-solid fluidized bed. This thesis focuses on the hydrodynamic aspects of such a 3-phase fluidized bed; a general design strategy was developed. Within this 3-phase system, a liquid-solid fluidized bed consisting of biocatalytic gel beads in a continuous medium phase, and a liquid-liquid extraction column or spray column, consisting of organic droplets in a continuous medium phase can be discerned. The hydrodynamic characteristics of these constituent 2-phase systems were studied as well. At the end this thesis reviews the current status of the newly developed 3-phase liquid-liquid-solid fluidized-bed bioreactor; it outlines additional research to be performed for a full understanding of its hydrodynamicbehavior. Additional steps that have to be taken for practical implementation of the 3-phase fluidized bed as a new type of bioreactor are emphasized.