Bioreactor scale-down

Scale-down design based on regime analysis was introduced by Oosterhuis in 1984 [11] in a study of the process for gluconic acid production. Oosterhuis proposed four steps for scaling down  

Oxygen consumption toe = Zero-order Monod kinetics, Cq tr,r = —First-order Monod kinetics, OC 2 2 

Substrate consumption tor = nJ— Zero-order Monod Kinetics 

area for heat transfer Cq, dissolved oxygen concentration impeller diameter Dj, tank diameter H, Henry constant k a, volumetric oxygen transfer coefficient /tq, oxygen saturation 

As the second example, the scale-down study performed by Oosterhuis [11] is summarized. Table 2.2 lists characteristic times based on estimations for a 25 m STR equipped with two standard Rushton impellers used for gluconic acid production. In this example, the time constant for oxygen transfer (Iqt) longer than that for oxygen consumption (loc) therefore oxygen limitation is 

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Sweere, A. P. J., Luyben, K. Ch. A. M. and Kossen, N. W. F. (1987) Regime Analysis and Scale-Down Tools to Investigate the Performance of Bioreactors. Enzyme Microb. TechnoL, 9, 386-398. 

An example of the application of a unified model to the design of a three-phase, fluidized bed bioreactor is the scale down, scale up procedure. A model of the full scale reactor is developed, then is used to design... 

Bioreactor operation and scale-up are not completely independent processes and should be assessed as different aspects of the same problem. Bioreactor operation must then consider process scale-up not only as the next step but also, as in the classic scale-down method, as a starting point. This means that bioreaction design should be done in scalable systems. A scalable system has to be inherently simple and reliable in operation and control, for easy validation and control in a production facility [56]. 

Osterhuis, N. M. G., Scale-Up of Bioreactors A Scaled-Down Approach, Ph.D. Thesis. Delft University of Technology, Delft, The Netherlands, 1984. 

Zeilinger K, Schreiter T, Darnell M et al (2011) Scaling down of a clinical three-dimensional perfusion multicompartment hollow fiber liver bioreactor developed for extracorporeal liver support to an analytical scale device useful for hepatic pharmacological in vitro studies. Tissue Eng Part C Methods 17(5) 549-556... 

Rosello Sastre R, Csbgor Z, Pemer-Nochta I, Fleck-Schneider P, Posten C Scale-down of tnicroalgae cultivations in tuhular photo-bioreactors—a conceptual approach, J Biotechnol 132(2) 127-133, 2007. 

Noorman H (1993) Bioreactor performance on 30 m scale verification of a scale-down/CFS approach. Technical report, Instituttet for Bioteknologi, Damarks Tekniske Ho-jskole, Lyngy, Denmark... 

The process kinetic analysis is carried out in two different types of reactors. The so-called perfect bioreactor is used for obtaining true kinetic data. This laboratory reactor must therefore meet certain requirements with regard to all possible transport phenomena (see Sect. 4.2). A so-called bioreactor model is a scaled-down bioreactor with some geometrical similarity to the production unit. Here, significant transport phenomena (cf. Chap. 3) can be studied and quantified with a physical system in a first step. 

Figure 2.1 Schematic view of the different zones that may appear in a large-scale, fed-batch bioreactor due to deficient mixing. Cells transit continuously through the various zones, leading to complex physiological transient responses. The characterization of such responses is a central theme of the scale-down approach, (a) As the pH control agent in the bioreactor is usually added to...

In a one-compartment scale-down system (OCSDS), heterogeneous conditions are created by the oscillatory variation of the operational set up of the bioreactor. Agitation rate, air flow rate, pressure, or substrate addition can be varied to reproduce the frequencies and oscillation periods of parameters such as DOT or... 

Improvements Based on Scale-Down Studies Bioreactor Design and Cell Engineering... 

Response of Corynebacterium glutamicum exposed to oscillating cultivation conditions in a two- and a novel three-compartment scale-down bioreactor. Biotechnol. Bioeng., 112 (6), 1220-1231. 

Delvigne, F. (2012) Scale-down assessment of the sensitivity of Yarrowia lipolytica to oxygen transfer and foam management in bioreactors investigation of the underlying physiological mechanisms. /. Ind. Microbiol. Biotechnol., 39, 337-346. 

P. (2011) Accumulation of amino acids deriving from pyruvate in Escherichia coli W3110 during fed-batch cultivation in a two-compartment scale-down bioreactor. Adv. Biosci. Biotechnol, 2 (5), 336-339. 

Sieck, J.B., Cordes, X, Budach, W.E., Rhiel, M.H. et al. (2013) Development of a scale-down model of hydrodynamic stress to study the performance of an industrial CHO cell line under simulated production scale bioreactor conditions. J. Biotechnol, 164 (1), 41-49. 

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