Bioreactor scale‐down studies of suspended plant cell cultures

Abstract

The effect of dissolved oxygen fluctuations on suspended plant cells was investigated using a scale‐down stirred bioreactor system to simulate the heterogeneous conditions found in large‐scale vessels. Transgenic Nicotiana tabacum cells expressing IgG1 antibody and Thalictrum minus cells producing berberine were subjected to gas switching cycles based on a stochastic model of log‐normal circulation time distributions. Because pumping severely damaged the cells, the scale‐down approach was restricted to a single‐vessel system. Dissolved oxygen oscillations of amplitude about ±5% air saturation were achieved in the N. tabacum cultures; however, most simulations produced highly damped fluctuations due to oxygen transfer limitations and no significant effect on the cultures was observed. In contrast, berberine production by T. minus cells was reduced when fluctuations of ±10–15% air saturation were superimposed on mean dissolved oxygen tensions of 25 and 35% air saturation. This work demonstrates that dissolved oxygen gradients such as those found in large‐scale mixing vessels can be detrimental to plant cell cultures even when sufficient average dissolved oxygen levels are provided. © 2018 American Institute of Chemical Engineers AIChE J, 64: 4281–4288, 2018

Engineering Considerations to Produce Bioactive Compounds from Plant Cell Suspension Culture in Bioreactors

“…Another important parameter considered for the establishment of aeration conditions is the oxygen transfer rate (OTR); it must be high enough to provide the required oxygen concentration to meet the respiratory demands of the cells (OUR), favoring the growth and production of the desired compounds, but not too high that it can hinder them. To overcome these difficulties, the concentration of dissolved oxygen must be kept above the critical level of cell oxygen consumption, which has been reported to be 15-20% oxygen saturation content in pure water (1.3 to 1.6 g/m 3 ) [11,77]. Dissolved oxygen concentration is not a variable that can be used for scaling criteria, and instead the volumetric mass transfer coefficient (kLa) and the air flow rate are used (vvm).…”

Kinetics of Whole Cells and Ethanol Production from Candida tropicalis TISTR 5306 Cultivation in Batch and Fed-batch Modes Using Assorted Grade Fresh Longan Juice

“…(B.2) for n = 2.1, 2.2) proposed here would be useful for simulation and optimization applications in batch (Yuvadetkun et al 2017), fed batch (current study), and continuous processes (Nunta et al 2019). The mathematical model could be incorporated into the mass balance equations for a specific production process with intermittent, regular pulse, or continuous feeding strategies (Cheung et al 2018). The kinetic parameters in the model could be thoroughly searched and determined based on a written Visual Basic for Applications (VBA) source code in Microsoft ® Excel (Nunta et al 2019, Cheung et al 2018, Leksawasdi et al 2005a,b, 2003 after implementing numerical integration strategies of Eq.…”

“…The mathematical model could be incorporated into the mass balance equations for a specific production process with intermittent, regular pulse, or continuous feeding strategies (Cheung et al 2018). The kinetic parameters in the model could be thoroughly searched and determined based on a written Visual Basic for Applications (VBA) source code in Microsoft ® Excel (Nunta et al 2019, Cheung et al 2018, Leksawasdi et al 2005a,b, 2003 after implementing numerical integration strategies of Eq. (A), (B.1), and (B.2) to regress multiple experimental data sets in a series of batch cultivation system with various levels of initial substrates concentration (pure substrates or variety of longan related products).…”