Large Scale Bioreactors – Insight Into a Black Box


Aerated stirred tank reactors (STR) are often used for mixing, heat- and mass transfer processes in chemical and biochemical engineering. In pharmaceutical industry for instance, mixing is of great importance to minimize concentration gradients. Furthermore mass transfer of oxygen from gaseous bubbles into the fermentation broth needs to be maximized at low energy dissipation rates. For a reliable design and scale up of such processes a profound understanding of hydrodynamics and mass transfer is required. Despite the fact that the complex two phase flow behaviour in such reactors has been investigated intensively in the last decades [1 ,2, 3], there is still a lack of knowledge especially for large scale applications, where the influence of the inhomogeneity of the gas phase is much higher than in small scale reactors. Further experiments in large scale needs to be conducted for a better understanding. On the other hand production and large scale systems are usually made of stainless steel with no or only poor optical access. This however, does not allow the detection of local phenomena and inhomogeneities or a detailed knowledge of the effect caused by gassing and stirring as well as their interaction. Therefore, the physical effects are not accessible in detail and process knowledge is based on few integral measurements of mass transfer coefficients and the mixing time with a small number of probes.

To overcome this gap an acrylic glass reactor has been designed and erected on industrial scale (15 000 L) together with Boehringer Ingelheim Pharma GmbH & Co. KG. The optical access of this reactor enables us detailed studies on local flow patterns and their influences on mixing and mass transfer. 


Mixing time

A crucial parameter for the characterization of stirred tank reactors is the mixing time that is necessary to achieve a certain degree of homogenization. Usually the mixing time in large scale systems is measured locally with conductivity probes. The optical access of the acrylic glass reactor to the liquid volume enables us to measure mixing times with the decolourization method with high resolution transient photo series. The advantage of the colorimetry is its ability to visualize dead flow zones as well as local and global flow structures simultaneously. The results are compared to transient computational fluid dynamic (CFD) simulations and used to improve these predictive methods.

Oxygen Mass Transfer

Especially for aerobic processes, the supply of oxygen is of high importance. For this reason, the liquid is being gassed with air or pure oxygen. Resulting from the concentration difference Dc a transfer of mass from the gaseous phase with a high concentration of oxygen to the liquid with the lower concentration is taking place. This process can quantitatively be determined by using the volumetric mass transfer coefficient which can be measured by different methods. The simplest one is the gassing out method where at first the oxygen is stripped out with nitrogen. After that the reactor is aerated with air or oxygen and the increasing oxygen concentration is logged for the desired process parameter. In literature many correlations for the volumetric mass transfer are available and often in the form of 

as a function of the power input, and the superficial gas velocity. 


The reactor is equipped with a high amount of sockets were different probes can be applied. It is possible to measure:

  • Temperature
  • Pressure
  • Oxygen concentrations
  • Carbon dioxide concentration
  • pH
  • Conductivity...
Figure 1: Example of the arrangment of different oxygen probes Figure 2: Set-Up for decolourisation measurement

Figure 1 shows the installation for the measurement of the mass transfer coefficient at different operation condition. By applying the oxygen probes at different heights of the reactor, the mass transfer as the function of the height can be detected.

Figure 2 gives the set-up for the measurement of the decolourisation measurement. A light source at the back of the reactor and a diffusor between the light and the reactor leads to an illumination of the whole reactor. With a camera at the opposite site, the decolourisation process can be followed. 


[1] A. W. Nienow; Appl. Mech. Rev 51(1), 3-32 

[2] M.M.C.G.Warmoeskerken, J. M.Smith; Chem. Eng. Sci., 40 (1985), pp. 2063-2071

[3] M. Zlokarnik, H. Judat; Chemie-Ing.-Techn. 39. Jahrg. 1967 1 (20), pp. 1163-1168