scholarly journals Optimization of lentiviral vector production for scale-up in fixed-bed bioreactor

Gene Therapy ◽  
2017 ◽  
Vol 25 (1) ◽  
pp. 39-46 ◽  
Author(s):  
A J Valkama ◽  
H M Leinonen ◽  
E M Lipponen ◽  
V Turkki ◽  
J Malinen ◽  
...  
2011 ◽  
Vol 6 (1) ◽  
Author(s):  
Valérie Gelbgras ◽  
Christophe E Wylock ◽  
Jean-Christophe Drugmand ◽  
Benoît Haut

In this work, a mathematical model of a fixed-bed bioreactor for the animal cell culture is developed to study the optimization and the scale-up of this bioreactor. Several cell populations are considered: the cells in suspension in the medium at the beginning of the process and the adhering cells to the fixed-bed. The model includes a capture rate kinetic of the cells in suspension by the fixed-bed and a spatial distribution of the nutrient and by-product concentrations in the fixed-bed. Therefore, the model reports the potential gradients of the cell concentrations in the fixed-bed. Some model parameters are experimentally identified and the model is validated using experimental data obtained with two pilot bioreactors. The model is used as a simulation tool to study the influence of the bioreactor design or the velocity field of the culture medium on the cell concentration gradients in the fixed-bed bioreactor and to optimize the operating conditions, the design, and the scale-up of this bioreactor.


1985 ◽  
Vol 50 (10) ◽  
pp. 2122-2133 ◽  
Author(s):  
Jindřich Zahradník ◽  
Marie Fialová ◽  
Jan Škoda ◽  
Helena Škodová

An experimental study was carried out aimed at establishing a data base for an optimum design of a continuous flow fixed-bed reactor for biotransformation of ammonium fumarate to L-aspartic acid catalyzed by immobilized cells of the strain Escherichia alcalescens dispar group. The experimental program included studies of the effect of reactor geometry, catalytic particle size, and packed bed arrangement on reactor hydrodynamics and on the rate of substrate conversion. An expression for the effective reaction rate was derived including the effect of mass transfer and conditions of the safe conversion-data scale-up were defined. Suggestions for the design of a pilot plant reactor (100 t/year) were formulated and decisive design parameters of such reactor were estimated for several variants of problem formulation.


2015 ◽  
Vol 266 ◽  
pp. 233-240 ◽  
Author(s):  
C. Cortés-Lorenzo ◽  
M. Rodríguez-Díaz ◽  
D. Sipkema ◽  
B. Juárez-Jiménez ◽  
B. Rodelas ◽  
...  

2017 ◽  
Vol 11 (1) ◽  
pp. 16-25 ◽  
Author(s):  
Rebecca Faschian ◽  
Ilyas Eren ◽  
Steven Minden ◽  
Ralf Pörtner

Fixed-bed processes, where cells are immobilized within macroporous carriers, are a promising alternative to processes with suspended cells. A scale-up concept is presented in order to evaluate the performance as part of process design of fixed-bed processes. Therefore,Lactococcus lactiscultivation in chemostat and batch mode was compared to fixed bed cultures on three different scales, the smallest being the downscaledMultifermwith 10 mL fixed bed units, the second a 100 mL fixed-bed reactor and the third a pilot scale reactor with 1 L fixed bed volume. As expected, the volume specific lactate productivity of all cultivations was dependent on dilution rate. In suspension chemostat culture a maximum of 2.3 g·L-1·h-1was reached. Due to cell retention in the fixed-beds, productivity increased up to 8.29 g·L-1·h-1at a dilution rate of D = 1.16 h-1(corresponding to 2.4·µmax) on pilot scale. For all fixed bed cultures a common spline was obtained indicating a good scale-up performance.


2021 ◽  
Vol 891 ◽  
pp. 31-36
Author(s):  
Jirah Emmanuel T. Nolasco ◽  
Camille Margaret S. Alvarillo ◽  
Joshua L. Chua ◽  
Ysabel Marie C. Gonzales ◽  
Jem Valerie D. Perez

Continuous fixed-bed column studies were performed using nanocomposite beads made up of chitosan, polyethyleneimine, and graphene oxide as adsorbents for the removal of methyl orange (MO) in water. The effects of different operating parameters such as initial MO concentration (5, 10, and 15 ppm), bed height (10, 17.5, and 25 cm), and flow rate (27, 43, and 58 mL/min) were investigated using an upward-flow fixed-bed column set-up. The breakthrough curves generated were fitted with Adams-Bohart, Thomas, Yoon-Nelson, and Yan et al. models. The results showed that Yan et al. model agreed best with the breakthrough curves having an R2 as high as 0.9917. Lastly, design parameters for a large-scale adsorption column were determined via scale-up approach using the parameters obtained from column runs.


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