Disposable Bioreactors for Cells and Microbes - Productivities similar to those achieved with stirred tanks can be achieved with disposable bioreactors. - BioPharm International
The kLa-values for the Biostat CultiBag RM at full-rocking speed, angle, and gas flow using air were 22.0 h-1 for the 2-L
system and 6.0 h-1 for the 20-L system. Using pure oxygen as process gas, the KLa-values increased to 43.2 h-1 and 12.9 h-1,
respectively.
Figure 3
Growth of the C. diphtheria was assessed (Figure 1). The optical densities of the cultures were measured and the DO was monitored in the CultiBag RM
using the disposable optical DO probes. During the course of the cultivation, the DO dropped to around 25% because of the
limited oxygen transfer by headspace aeration. However, the culture reached an OD590 of five in the CultiBag RM and 7.3 in
the stainless-steel fermenter after an 8-h cultivation period, indicating that the BIOSTAT CultiBag RM is well suited for
cultivation of C. diphteriae for seed inoculum.
Figure 4
CHO-X evaluation. A commercial CHO cell line was evaluated using standard rocking and cultivation parameters. The cell growth shown in Figure
2 was slightly lower than the STR but the viability was higher at the end (Figure 3). Figure 4 shows that the overall production
was greater than stirred-tank bioreactors.
Figure 5
To demonstrate the reliability of disposable sensor technology, the real time data plot is shown in Figure 5. The pH control
is shown to be within +/–0.1 pH units and equivalent to traditional sensors.
Table 2. Cell culture performance of the CultiBag bioreactor compared to the STR
CHO-A cell line evaluation. Overall cell culture performance of the CultiBag bioreactor was comparable to the STR (Table 2). The final RP HPLC titer value
and the average specific productivity of CultiBag were higher than that of the STR. Temperature control was comparable to
a conventional bioreactor (within +/- 0.5 °C). Cell culture performance of the CultiBag bioreactor was comparable to the STR's.
Some early stage proportional-integral-derivative controller (PID) loops were tuned to achieve better control of pH and DO.
The average specific productivity of CultiBag was higher than that of the STR's. Without pH and DO control, the Wave bioreactor
demonstrated different cell culture performance compared to the CultiBag bioreactor in terms of higher final cumulative viable
cell count (CVC) value, lower RP HPLC titer, and lower average specific productivity.
Figure 6
CHO-S and CHO-K1 evaluation. The growth characteristics of the CHO-S and CHO-K1 were also similar, with both cell lines reaching comparable levels in both
types of bioreactor (Figure 6). The CHO-S showed better growth, reaching higher cell densities then the CHO-K1, probably reflecting
the better adaptation to suspension culture.
Figure 7
Figure 7 shows the glucose and lactate profile of the CHO-S cultivation. In this instance, the glucose consumption of the
cells grown in the B-DCU STR was higher. Consequently, the lactate build up was also higher. This observation is congruent
with the slightly higher viable cell density reached in the B-DCU.
