Bioreactors maximized productivity

Bioreactors are the core of bioprocesses, as they provide the key link between the initial feedstock and the product, where chemical modifications are carried out. Vessels used as bioreactors have to be designed and operated in such a manner to accommodate the requirements of a given type of cells or enzymes to perform in conditions that maximize productivity. Therefore, bioreactor engineering is a cross-disciplinary area, where biology and engineering interact closely. Key issues for bioreactor design and operation are addressed and illustrated by some examples that highlight the relevance of biochemical process industry. 

Production of Lignin Peroxidase. Medium for the inoculum was rich in yeast extract (25 g/1) and glucose (25 g/l) to promote maximal growth of the mycelia. The inoculum of Phanerochaete chrysosporium ATCC 24725 was first cultivated for 3 days at 30°C in five litres of medium divided in five shake flasks. The shake flask batches were transferred to a 100 litre bioreactor and cultivated again for 3 days at 30°C. The batches were stirred and aerated to obtain maximal growth of mycelia. 

Production. The inoculum grew vigorously in the rich yeast extract containing media and produced a thick viscous dispersion in the stirred tank bioreactor. No lignin peroxidase activity could be detected at this stage. When transferred to the 1000 1 production bioreactor, the mycelium of P.chrysosporium attached completely to the nylon wool sheets within a few hours after inoculation and the medium remained completely clear throughout the cultivation. The enzyme had to be harvested immediately after the maximal activity level was reached due to its... 

SMB bioreactor for high fructose syrup by glucose isomerization Maximization of productivity of fructose and minimizing desorbent used. NSGA-II-JG Both operation and design of the SMB bioreactor were optimized. Zhang et al. (2004)... 

Fed-batch bioreactors for (a) lysine and (b) protein by recombinant bacteria The objectives are (1) maximization of both productivity and yield of lysine, and (2) maximization of amount of protein produced while minimizing volume of inducer added. NSGA-11 The two applications were solved as single objective optimization problems in the earlier studies. Sarkar and Modak (2005)... 

Another important aspect of process development is pH control. The basal medium is formulated to contain a buffer compatible with cell growth the current industry standard is bicarbonate. Bicarbonate is in equilibrium with CO2 such that bioreactor pH can be lowered by addition of CO2 and raised by addition of a base (such as NaOH). Particularly at large scale, CO2 accumulation has been shown to be detrimental to bioreactor performance, and CO2 levels are lowered by stripping this dissolved gas with sparged nitrogen or air. Because cell growth is dependent on pH, optimization of this parameter allows for maximal cell mass accumulation and increased production of the product of interest. 

A few examples are in order. The first involves bioreactors filled with cells cultivated to produce economically important enzymes. In order to maximize enzyme production, overproducing strains of organisms are used (Shuler and Kargi, 1992). These BU must be fed extra nutrients and energy in order to overcome the inefficiency of producing more of these enzymes than they actually need. 

The fed-batch and batch cultivation systems share the same cleaning and sterilization process in which the bioreactor operation is stopped and the bioreactor is emptied. This stoppage creates considerable costs and operational downtime. The repeated or cyclic system, which can be applied to both batch and fed-batch cultivation systems, may be installed in order to maximize the productivity. The cyclic cultivation system does not enter the cleaning and sterilization process, but rather empties a portion of the bioreactor while preserving part of the batch for the next cycle. Another method to increase productivity is cell retention techniques such as fluidized beds, membranes, or external separators. These options allow multiple cycles without cleaning and sterilization, which is initiated only if it is deemed that mutation risks exceed tolerable levels (Bellgardt, 2000b). 

Bioreactor design Working volume (L) Grapevine cv/sucrose (gL- ) Aeration (vvm)/ agitation (rpm) Maximal biomass (gFWL Biomass productivity (gFW ) L- day- ) References... 

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