How Multipurpose is a Disposable Bioreactor? - The authors discuss the use of single-use bioreactors throughout industry. - BioPharm International


How Multipurpose is a Disposable Bioreactor?
The authors discuss the use of single-use bioreactors throughout industry.

BioPharm International
Volume 24, Issue 3, pp. 51-56


Figure 2. CELL-tainer single use bioreactor. (COURTESY: HAN BIOCENTRE)
The CELL-tainer technology (see Figure 2) is based on a 2D rocking motion and application of a pillow-shaped or rectangular three-dimensional bag. Due to the two-dimensional rocking motion (in vertical and horizontal direction at the same time), the mass transfer is much higher when compared with other rocking systems (4).

High mass transfer has the potential of supporting higher cell densities, better stripping capacity of CO2, cell culture application as well as application in microbial and fungal fermentation. Besides improvement of the mass transfer, this bioreactor offers a removable segmentation of the bags, which makes it possible to start at volumes as low as 200-250mL and expand the culture in one-and-the-same bag up to working volumes of 15 L. The sensors, including an electrochemical sensor for pH and a polarographic sensor for DO—both in a disposable format—are mounted in the bottom of the bag and positioned in small cups, which guarantees proper process control even with low volumes under shaking conditions. Because traditional sensor technology is used, the range of measurement for pH is not restricted (pH: 0–14) as it is with optical sensors (pH: 6.5–8.0).

Temperature control of the bioreactor bag is located inside the incubator cabinet and by convection. No heating blanket is applied. When heat is generated by the culture, (e.g., with microbial fermentation, cooling is required). The CELL-tainer is equipped with an integrated cooling plate in the rocking platform. Using a temperature difference of 25 C, the cooling capacity is 500W, which is sufficient for a high density E. coli culture.

Figure 3. Mass transfer in a CELL-tainer bioreactor (tap water, 20 C) (Data CELLution Biotech) compared to the Wave Bioreactor.
Investigation of the mass transfer, shows that the CELL-tainer covers a wide range of mass transfer values (see Figure 3). This is far beyond the capabilities of the traditional rocking type of bioreactors.

In most mammalian cultures, the mass transfer for oxygen seems to be sufficient to support high cell densities, at least in the stirred bioreactors. To enhance oxygen transfer, stirred bioreactor (micro-) spargers are applied and air may be enriched with oxygen. In both stirred and wave type single-use bioreactors, the exchange of CO2 might be limited due to a lower mass transfer coefficient and due to limitations in stripping efficiency. As the mass transfer coefficient in the CELL-tainer bioreactor is much higher than in wave type and stirred single-use bioreactors, the liquid phase CO2 concentration is always in equilibrium with the gas phase CO2 concentration. This results in less CO2 build-up in the liquid phase, which results in reduced alkaline addition, and which benefits the culture as a whole.

The mass transfer that can be achieved in the CELL-tainer bioreactor is significantly higher (k|a > 300 hr-1) than that seen in the wave type bioreactors and that therefore opens the application of single-use equipment for microbial fermentations as well.

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