Hydrodynamics of Stirred Bioreactors

1998 ◽  
Vol 51 (1) ◽  
pp. 3-32 ◽  
Author(s):  
A. W. Nienow

This review of the hydrodynamics of stirred bioreactors begins with an introduction to the agitation problems of particular concern in such systems. This is followed by a brief review of some basic concepts in turbulence and rheology of relevance to bioreactors. Important aspects of single phase mixing in low viscosity, high viscosity and Theologically complex broths are then covered in some detail including flow patterns, power number versus Reynolds number plots (including the modification of the latter to allow for shear thinning broths), flow numbers, energy dissipation rates and flow close to impellers and between multiple impeller systems. From these basic principles, the problem of homogenization is then covered in depth because of its significance for bioreactor performance. Aeration concepts are then introduced and the behavior of traditional Rushton turbine impellers is then treated in detail, covering the flow patterns, aerated power characteristics, mixing time and scale-up considerations. The weaknesses of the Rushton turbine are then discussed which leads into a section describing how more modern impellers are able to improve on many of these, especially emphasising their ability to introduce more energy dissipation into the broth and handle more air before flooding, both of which enhance oxygen transfer. The improvement in bulk blending found with multiple axial flow agitators is brought out too. Finally, the retrofitting of fermenters originally containing Rushton turbines with these more modern impellers is discussed. In conclusion, it is clear that there have been substantial increases in the understanding of stirred bioreactor hydrodynamics. However, whilst further understanding will occur within the framework discussed here, the expectation must be that computational fluid dynamics will increase in importance in spite of the difficulty of handling complex rheology, multiphase systems and biological responses. This review article has 135 references.

2007 ◽  
Vol 13 (1) ◽  
pp. 1-20 ◽  
Author(s):  
Dan Cascaval ◽  
Anca-Irina Galaction ◽  
Elena Folescu

Although radial impellers, especially the Rushton turbine, are widely used in stirred bioreactors, their applicability is limited by the high apparent viscosities of the broth. Beside the intensification of broth circulation, the energetic efficiency and the shear effects on biocatalysts must be taken into account to select the optimum impeller or impellers combination. In this context, the paper presents a comparative study on the efficiency of seven different radial impellers for simulated broth mixing in a stirred bioreactor. The analysis was made by means of the mixing time values obtained by vertically changing the position of the pH-sensor in the broths, in correlation with the energy consumption needed for a certain level of mixing time or for the uniform distribution of the mixing intensity into the bulk volume of the broths.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Pouria Fattahi ◽  
Ali Rahimian ◽  
Michael Q. Slama ◽  
Kihak Gwon ◽  
Alan M. Gonzalez-Suarez ◽  
...  

AbstractCellular therapies based on human pluripotent stem cells (hPSCs) offer considerable promise for treating numerous diseases including diabetes and end stage liver failure. Stem cell spheroids may be cultured in stirred bioreactors to scale up cell production to cell numbers relevant for use in humans. Despite significant progress in bioreactor culture of stem cells, areas for improvement remain. In this study, we demonstrate that microfluidic encapsulation of hPSCs and formation of spheroids. A co-axial droplet microfluidic device was used to fabricate 400 μm diameter capsules with a poly(ethylene glycol) hydrogel shell and an aqueous core. Spheroid formation was demonstrated for three hPSC lines to highlight broad utility of this encapsulation technology. In-capsule differentiation of stem cell spheroids into pancreatic β-cells in suspension culture was also demonstrated.


2016 ◽  
Vol 10 (1) ◽  
pp. 88-109 ◽  
Author(s):  
Narges Ghobadi ◽  
Chiaki Ogino ◽  
Naoto Ohmura

Background: The intensification of fermentation in stirred bioreactors is an attractive approach for commercial interests and industries that work with biochemical products. Alpha amylase is an enzymatic bio-products that is produced largely from Aspergillus oryzae. Using adaptable agitator can be an efficient way for stirred fermentation. Objective: This study, concentrated on enhancing the mixing process in order to intensify Aspergillus oryzae fermentation. A straight type of Maxblend® impeller was used as an agitator to investigate the incubation parameters compared with the use of a 6-blade double Rushton turbine. Method: Stirred fermentation was done in batch condition. Effect of flow pattern of mixing on fermentation parameters was investigated after each sampling. Results: The results showed that the Maxblend® significantly intensified both enzyme activity and growth rate at low and moderate rates of power consumption (P). The main reason for the decreases in the growth rate and the enzyme activity during agitation by the Rushton turbine at low and high Pv was the lack of oxygen and mycelial damage, respectively. Additionally, use of the Maxblend® significantly intensified the KLa at low and moderate rates of power consumption. Conclusion: Axial and uniform mixing by Maxblend® impeller was resulted in improving the fermentation characteristics and enzyme activity.


2002 ◽  
Vol 56 (12) ◽  
pp. 506-513 ◽  
Author(s):  
Dan Cascaval ◽  
Corneliu Oniscu ◽  
Anca-Irina Galaction ◽  
Fiorina Ungureanu

This paper presents the experiments on mixing efficiency for aerated media for a laboratory stirred bioreactor with a double turbine impeller. The effects of stirrer rotation speed, air volumetric flow rate and stirrer position on the shaft on mixing time for aerated water and simulated broths (CMCNa solutions) were analyzed. Compared to non-aerated broths, the results indicated that the variation of mixing time with the considered parameters is very different, due to the complex flow mechanism of the gas-liquid dispersion, a mechanism which is changed by changing the broth properties or fermentation conditions. Using the Statistics Toolbox of MATLAB some correlations between the mixing time and rotation speed, air volumetric flow rate and stirrer position on the shaft were established. The proposed equations agree well with the experiments, the average deviation being ?9.02%.


2007 ◽  
Vol 13 (1) ◽  
pp. 21-26 ◽  
Author(s):  
Anca-Irina Galaction ◽  
Elena Folescu ◽  
Dan Cascaval

Although radial impellers, especially the Rushton turbine, are widely used in stirred bioreactors, their applicability is limited by the high apparent viscosities of the broths. For optimizing mechanical mixing by selecting the appropriate impeller for a specific fermentation broth or process, the comparative analysis of the mixing efficiency, energy costs and shear effects on the biocatalysts is required. By means of this analysis, three different combinations of radial impellers for water and viscous simulated broths were selected for attaining optimum mixing in a bioreactor. The proposed impellers combinations offer the most intense and uniformly distributed mixing and the lowest specific power consumption required for reaching a maximum level of mixing time of less than one minute.


Processes ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 880
Author(s):  
Michael C. Martinetz ◽  
Florian Kaiser ◽  
Martin Kellner ◽  
Dominik Schlosser ◽  
Andreas Lange ◽  
...  

Multipurpose stirring and blending vessels equipped with various impeller systems are indispensable in the pharmaceutical industry because of the high flexibility necessary during multiproduct manufacturing. On the other hand, process scale-up and scale-down during process development and transfer from bench or pilot to manufacturing scale, or the design of so-called scale-down models (SDMs), is a difficult task due to the geometrical differences of used vessels. The present work comprises a hybrid approach to predict mixing times from pilot to manufacturing scale for geometrical nonsimilar vessels equipped with single top, bottom or multiple eccentrically located impellers. The developed hybrid approach is based on the experimental characterization of mixing time in the dedicated equipment and evaluation of the vessel-averaged energy dissipation rate employing computational fluid dynamics (CFD) using single-phase steady-state simulations. Obtained data are consequently used to develop a correlation of mixing time as a function of vessel filling volume and vessel-averaged energy dissipation rate, which enables the prediction of mixing times in specific vessels based on the process parameters. Predicted mixing times are in good agreement with those simulated using time-dependent CFD simulations for tested operating conditions.


Processes ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 464
Author(s):  
Xingren Jiang ◽  
Ning Yang ◽  
Rijie Wang

Continuous manufacturing has received increasing interest because of the advantages of intrinsic safety and enhanced mass transfer in the pharmaceutical industry. However, the difficulty for scale-up has limited the application of continuous manufacturing for a long time. Recently, the tubular flow reactor equipped with the Kenics static mixer appears to be a solution for the continuous process scale-up. Although many influence factors on the mixing performance in the Kenics static mixer have been investigated, little research has been carried out on the aspect ratio. In this study, we used the coefficient of variation as the mixing evaluation index to investigate the effect of the aspect ratio (0.2–2) on the Kenics static mixer’s mixing performance. The results indicate that a low aspect ratio helps obtain a shorter mixing time and mixer length. This study suggests that adjusting the aspect ratio of the Kenics static mixer can be a new strategy for the scale-up of a continuous process in the pharmaceutical industry.


2013 ◽  
Vol 102 ◽  
pp. 1-9 ◽  
Author(s):  
Mauro Cavinato ◽  
Riccardo Artoni ◽  
Massimo Bresciani ◽  
Paolo Canu ◽  
Andrea C. Santomaso

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