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Biotechnology Advances 27 (2009) 153–176

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Biotechnology Advances
j o u r n a l h o m e p a g e : w w w. e l s e v i e r. c o m / l o c a t e / b i o t e c h a d v

Research review paper

Bioreactor scale-up and oxygen transfer rate in microbial processes: An overview
Felix Garcia-Ochoa ⁎, Emilio Gomez
Dept. Ingeniería Química. FacultadQuímicas. Universidad Complutense. 28040-Madrid, Spain

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In aerobic bioprocesses, oxygen is a key substrate; due to its low solubility in broths (aqueous solutions), a continuous supply is needed. The oxygen transfer rate (OTR) must be known, and if possible predicted to achieve an optimum design operation and scale-up of bioreactors. Many studies have beenconducted to enhance the efficiency of oxygen transfer. The dissolved oxygen concentration in a suspension of aerobic microorganisms depends on the rate of oxygen transfer from the gas phase to the liquid, on the rate at which oxygen is transported into the cells (where it is consumed), and on the oxygen uptake rate (OUR) by the microorganism for growth, maintenance and production. The gas–liquidmass transfer in a bioprocess is strongly influenced by the hydrodynamic conditions in the bioreactors. These conditions are known to be a function of energy dissipation that depends on the operational conditions, the physicochemical properties of the culture, the geometrical parameters of the bioreactor and also on the presence of oxygen consuming cells. Stirred tank and bubble column (of varioustypes) bioreactors are widely used in a large variety of bioprocesses (such as aerobic fermentation and biological wastewater treatments, among others). Stirred tanks bioreactors provide high values of mass and heat transfer rates and excellent mixing. In these systems, a high number of variables affect the mass transfer and mixing, but the most important among them are stirrer speed, type and numberof stirrers and gas flow rate used. In bubble columns and airlifts, the lowshear environment compared to the stirred tanks has enabled successful cultivation of shear sensitive and filamentous cells. Oxygen transfer is often the rate-limiting step in the aerobic bioprocess due to the low solubility of oxygen in the medium. The correct measurement and/or prediction of the volumetric mass transfercoefficient, (kLa), is a crucial step in the design, operation and scale-up of bioreactors. The present work is aimed at the reviewing of the oxygen transfer rate (OTR) in bioprocesses to provide a better knowledge about the selection, design, scale-up and development of bioreactors. First, the most used measuring methods are revised; then the main empirical equations, including those usingdimensionless numbers, are considered. The possible increasing on OTR due to the oxygen consumption by the cells is taken into account through the use of the biological enhancement factor. Theoretical predictions of both the volumetric mass transfer coefficient and the enhancement factor that have been recently proposed are described; finally, different criteria for bioreactor scale-up are considered in thelight of the influence of OTR and OUR affecting the dissolved oxygen concentration in real bioprocess. © 2008 Elsevier Inc. All rights reserved.

Article history: Received 21 May 2008 Received in revised form 18 October 2008 Accepted 26 October 2008 Available online 12 November 2008 Keywords: Oxygen transfer rate Bioreactors scale-up Microbial processes Gas–liquid interface

Contents 1. 2.Introduction . . . . . . . . . . . . . . . . . . . 1.1. Oxygen transfer rate (OTR) description . . . Experimental determination of the volumetric mass 2.1. Measuring methods of kLa without biological 2.2. Chemical methods . . . . . . . . . . . . 2.3. Sodium sulfite oxidation method . . . . . 2.4. Absorption of CO2 . . . . . . . . . . . . 2.5. Physical methods . . . . . . . . . . . . . 2.6. Dynamic...