Scalability of the Mobius CellReady Single-use Bioreactor Systems - The author defines the process-design space and demonstrates scalability of a single-use, stirred-tank bioreactor. - BioPharm

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Scalability of the Mobius CellReady Single-use Bioreactor Systems
The author defines the process-design space and demonstrates scalability of a single-use, stirred-tank bioreactor.


BioPharm International Supplements
Volume 26, Issue 4, pp. s11-s17

EFFICIENT GAS TRANSFER

One of the most crucial scale-up parameters for bioreactors is mass transfer of gases. To provide an optimal environment for the cells, a bioreactor must be able to supply enough dissolved oxygen (O2) for efficient cellular metabolism as well as maintain an appropriate level of dissolved carbon dioxide (CO2). Sufficient O2/air delivery is required not only to support cell growth and protein production but also to prevent excessive CO2 accumulation in the media that can impact both of these critical performance endpoints (2). To assess the gas transfer efficiency of the Mobius CellReady bioreactor process containers, the volumetric mass-transfer coefficients (kLa) for oxygen were measured in each bioreactor process container using the static gassing out method.

kLa values were determined by filling the bioreactor process containers to the maximum working volume with a mock media (1X phosphate buffered saline (PBS), 2 g/L Pluronic F-68, 50 ppm Anti-foam C), and setting the temperature to 37 C. The dissolved oxygen was stripped from the bioreactors by supplying nitrogen gas via the microsparger. Once the dissolved oxygen (DO) concentration reached less than 2% air saturation, the nitrogen supply was turned off and air was sparged through the microsparger at flow rates ranging from 0.0025 vvm to 0.5 vvm at two different agitation rates. The DO concentration was recorded over time until the dissolved oxygen concentration in the media plateaued at the fully saturated value (100% air saturation). An air overlay gas was not used in these studies.

k L a Calculation


Figure 2A: kLa Scalability of the 50-L and 200-L Mobius CellReady bioreactor process containers. Each bar represents the average kLa value of n=3 at each air-flow rate and impeller agitation rate tested. Error bars represent the standard deviation of triplicate determinations.
The kLa value for each trial was calculated from the linear portion of the DO vs. time graph. To avoid subjectivity in determining the linear portion, the uniform DO interval used for the calculation was between 10% and 90% air saturation. The kLa values shown represent the slope of the line created by plotting ln((C*–Ct1)/(C*–Ct2)) versus time (t2–t1), where C* is fully saturated liquid, Ct1 is the percent air saturation at the initial time, Ct2 is the percent air saturation at time 2, and t1 and t2 are the initial time and time 2, respectively.


Figure 2B: kLa Scalability of the family of Mobius CellReady bioreactor systems. Each bar represents the average kLa value of n=3 at each air-flow rate and impeller agitation rate tested. Error bars represent the standard deviation of triplicate determinations.
As detailed in Table I, the impeller and sparger design and placement in the 50-L and 200-L bioreactor process containers are similar; however, the 3-L bioreactor is significantly different from the 50-L and 200-L bioreactor process containers. For example, in the 50-L and 200-L bioreactor process containers the membrane polyethylene microsparger is located directly beneath the impeller, while in the 3-L bioreactor a sintered polyethylene microsparger is located off to the side of the impeller. Also, the impeller blade shape differs between the bioreactors. A pitched blade impeller is found in the 50-L and 200-L bioreactor process containers while a marine impeller is found in the 3-L bioreactor. As shown in Figure 2A, the 50-L and 200-L bioreactor process containers, at the same power per unit volume, exhibit comparable kLa values. These two bioreactor process containers can achieve kLa values ranging from 4 hr-1 at the lowest agitation and air flow rates tested to 60 hr-1 at the highest agitation and air flow rates tested. Given the differences in the volume and design between the 3-L bioreactor and the 50-L and 200-L bioreactor process containers, it is not surprising that, at the same gas flow rates and power per unit volume, the kLa values are not immediately comparable. However as shown in Figure 2B, by adjusting the air flow rates, scalable kLa values between all three bioreactor systems at similar power per unit volumes can be achieved.


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