Pollard, David James; (1995) A study of fermentation heterogeneity in a pilot scale airlift bioreactor. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The extent of the heterogeneity in a large scale vessel can affect cell growth and product yields. Consequently, the examination of the impact of the engineering environment on the physiology of fermentation broths can lead to improved growth and production conditions which will be important for fermentation optimisation including scale up, design and operation of bioreactors. Bioreactor heterogeneity has been studied in a multiconfigurable pilot scale airlift reactor (0.25 m3) which can create different degrees of heterogeneity. Hydrodynamic and oxygen transfer performances of two air ring sparger configurations, ie. in the annulus or draft tube, in combination with a marine propeller fitted at the base of the reactor, were compared using Newtonian baker's yeast suspensions and batch cultures of non-Newtonian Saccharopolyspora erythraea. The cellular growth, morphology and productivity of the S. erythraea broths were also compared between the airlift reactor configurations and stirred tank. The comparison of gas holdup, liquid velocity and mixing times between the two sparger configurations with baker's yeast suspension was influenced by the ratio of the cross sectional area of the downcomer to the riser and the bubble flow regime. The achievement of a critical liquid height above the draft tube for optimal liquid mixing demonstrated the importance of the top section to the liquid mixing performance of the vessel. The local DOT and kLa values were greater in the downcomer than in the riser. This was caused by the high gas content, long gas residence times and smaller bubble diameter in the downcomer compared to the riser. The gas holdup, liquid circulation and oxygen transfer with conventional airlift operation were improved by operating the marine propeller in conjunction with the annulus ring sparger to draw liquid down the draft tube. This led to a reduction in the extreme DOT heterogeneity and a increase of the OUR of the yeast suspension. Maximum OUR was obtained when the lowest DOT of the cycling DOT was at or above 10% (air saturation). The OUR improved if the cells experienced the same DOT changes at a greater frequency. This indicated that cells could respond to rapid DOT changes around the vessel and so the cell metabolism was not based on an average DOT of the vessel. During the S. erythraea fermentations the enhancement of bubble coalescence with increasing apparent viscosity led to the reduction of the sectional gas holdups and local kLa values and the improvement of liquid mixing. The extent of the changes with increasing apparent viscosity were dependent on the broth morphology, reactor configurations and operating conditions. The relationships between broth rheology and the dry cell weight, morphology and liquid velocity were all influenced by the reactor configuration and operating conditions. DOT heterogeneity did not affect the growth of mycelial S. erythraea broths but the reduction of DOT heterogeneity improved the specific erythromycin production rate and final specific erythromycin production which was proportional to the energy dissipation rate. The study shows that an understanding of cell physiology and the effect of the engineering environment on their growth, productivity and morphology is essential for the enhancement of bioprocesses. The examination of reactor heterogeneity provides a better understanding of the effects of the translation of scale and as a result can lead to a more efficient process with improved productivity.

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