One of the functions of the Laboratory of Chemical Engineering of the University of Liege is to make its expertise available to industry. The laboratory recently published the results of a hydrodynamic study inside a disposable bioreactor used for animal cell cultures in the pharmaceutical industry. Because they enable companies to avoid the rigorous process involved in cleaning and sterilizing traditional stainless steel tanks, these disposable bioreactors are being progressively viewed as serious alternatives from an economical point of view. The performance of these bioreactors still needs to be assessed, particularly considering the unusual shapes they are designed in. This is a comprehensive study which bridges the gap between fundamental research and the economic requirements of the industrial world.  

In order to develop animal cell cultures, the pharmaceutical industry uses stainless steel tanks which require fastidious and costly cleaning and sterilization. More and more manufacturers are proposing an alternative which may seem crazy: plastic disposable bioreactors. The University community is asked to quantify the performance of these bioreactors and verify that they are as efficient as traditional bioreactors. Researchers at the Chemical Engineering Laboratory of the University of Liege were recently asked by the pharmaceutical giant GlaxoSmithKline (GSK) to characterize the liquid flow inside Nucleo bioreactor which is one of the bioreactors supplied by the company ATMI LifeSciences.

GSK had good reason to exercise a certain caution. As well as being disposable, these bioreactors are parallelepiped in shape but in the pharmaceutical industry it is widely believed that a cylindrically-shaped reactor is the best solution for fluid-mixture consistency and optimal cell-development conditions. The task given to the researchers, led by Marie-Laure Collignon and Sébastien Calvo, under the direction of Dominique Toye, was to verify the hydrodynamics inside the bioreactor. The analysis was intended to establish whether, for a similar amount of energy use, the mixture of fluids was as efficient as in traditional bioreactors. The results were published in January 2015 in the Biochemical Engineering Journal(1). The results spoke for themselves. Moreover, they illustrated a methodology and a development of useful tools available for a large number of applications both in fundamental research and in applied sciences.

Bioreactors for growing cells

This is a story that has its roots in a very precise stage of industrial vaccine production. “Traditionally, stainless steel reactors are used for animal cell cultures”, continues Dominique Toye, a lecturer at the Chemical Engineering Laboratory of the University of Liege. “Clearly, these are not jet engines. It would be more accurate to compare them to tanks or to large saucepans with a capacity of between 50 liters to several cubic meters. We call them “reactors” simply because they are containers in which we perform “reactions” on an industrial scale. These reactions can be chemical, biochemical or biological”.

The animal cells are then infected by a virus to allow them to develop antibodies used in the manufacture of vaccines. In order to reproduce, the cells need a food source (glucose, mineral salts…) and oxygen, present in the culture medium which the bioreactor is filled with. “There are two imperatives for optimal growth. Firstly, these reactors must remain sterile. Otherwise other stronger microorganisms could grow more rapidly in the same conditions to the detriment of the required cells. Then the system must be as homogenous as possible. The fluid must therefore be mixed with the aid of an agitator placed in the middle of the bioreactor. This agitator, which turns on itself like a propeller, enables the liquid to have sufficient speed to mix. However, its rotation speed must also be limited for at least two reasons. Excessive agitation could damage the cells, and the other reason is down to economics. More energy is required. There is therefore an optimal balance to be found”. The cylindrical tanks with concave bottoms that are generally used enable a good quality of mixing and are easy to clean because they do not have any angles that could lead to a build-up of dirt.

(1) Marie-Laure Collignon, Laurent Droissart, Angélique Delafosse, Sebastien Calvo, Steven Vanhamel, Roman Rodriguez, Tom Claes, Fabien Moncaubeig, Ludovic Peeters, Michel Crine, Dominique Toye, Hydrodynamics in a disposable rectangular parallelepiped stirred bioreactor with elliptic pendulum motion paddle, Biochemical Engineering Journal, Volume 93, 15 January 2015, Pages 212–221