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

MIXING


Table II: Tip speed, Reynolds number, and ungassed power-per-unit volume values for the 3-L Mobius CellReady bioreactor process container.
Mixing is a crucial bioreactor performance characteristic because it is responsible for minimizing gradients and maintaining control within the cell culture environment. Good mixing in a bioreactor strives for sufficient fluid pumping and turnover throughout the system to effectively create a single homogeneous environment which can be accurately monitored and controlled. Good mixing should evenly distribute bioreactor contents, helping to minimize zones of uneven cell density, pH, temperature, dissolved gases, and nutrient or waste concentrations, while minimizing the shear stress imparted on the cells by the fluid dynamics or the mixing element itself.


Table III: Tip speed, Reynolds number, and ungassed power-per-unit volume values for the 50-L Mobius CellReady bioreactor process container.
Although no single parameter can guarantee comparable process performance between stirred tank bioreactor systems, choosing an agitation rate that matches energy dissipation or power per unit volume (W/m3 ) is a common first approach (3, 4). The impeller design, fluid density, and agitation rate are considered in the power per unit volume (Po/V) equation, Po/V = Np x ρ x n3 x d5 , where Po is ungassed power, V is liquid volume, Np is impeller power number, d is impeller diameter, n is impeller agitation rate and ρ is fluid density. Using this scaling method, agitation rate is varied to maintain similar ungassed power-per-unit volume across vessels.


Table IV: Tip speed, Reynolds number, and ungassed power-per-unit volume values for the 200-L Mobius CellReady bioreactor process container.
The highest shear zones in a stirred tank bioreactor are often described as existing within the impeller zone. Because the outer edge of the impeller blades create shear as they rotate through the liquid, the impeller tip speed is often considered during bioreactor comparisons. The impeller tip speed calculation, π x d x n, where d is impeller diameter and n is agitation rate, however, does not take impeller design into consideration. Reynolds number (Re) can be considered when estimating fluid conditions at a given agitation rate by providing a ratio of the inertial forces to the viscous forces where Re = (ρ x n x d2 ) / . The fluid density is represented by ρ, n is agitation rate, d is impeller diameter, and is dynamic viscosity. The system is considered fully turbulent when Re > 10,000 (5, 6). The Reynolds number calculation is based on the assumption of a cylindrical tank with a centered rotating impeller and does not take impeller design into account. The Mobius CellReady 50-L and 200-L bioreactor process containers contain a bottom mounted, offset, pitched blade impeller and a baffle, which together increase the turbulence and improve overall mixing.

Tables II, III, and IV outline various tip speed, Reynolds number and ungassed power-per-unit volume values calculated for a range of applicable agitation rates for the 3-L, 50-L, and 200-L Mobius CellReady bioreactor process containers.


Figure 3: System average mixing times of the family of Mobius CellReady bioreactor systems. Data points represent the system average mixing time of n=15 individual trials. Error bars represent 1 standard error for each data point.
Mixing was evaluated for the 50-L and 200-L Mobius CellReady bioreactor process containers by observing conductivity probe response curves measured at four locations (top, middle, bottom, and inserted in the probe port of the Mobius SensorReady loop) within the system. The average of these four probes is considered the system average. A salt solution was introduced at the liquid surface and the T95 mixing time was determined for each of the four probe locations as the time when conductivity profiles had reached 95% of its final value. Each trial was performed in triplicate and results are shown in Figure 3. The Mobius CellReady 3-L bioreactor was evaluated in a similar manner, using just one conductivity probe inserted in the head plate probe port.


Table V: Comparison of operating parameters for 3-L, 50-L, and 200-L CellReady bioreactors.
Results of these studies show that the Mobius CellReady 50-L and 200-L bioreactor process containers demonstrated similar system average mixing times at equivalent power-per-unit volume. Mixing times for the 3-L bioreactor are significantly shorter than mixing times observed in the larger bioreactor process containers for similar power per unit volume. This is to be expected as larger liquid volumes result in longer fluid paths. To achieve a well mixed condition in the same amount of time, the fluid velocity would have to increase for the condition in the larger volume tank. As a guide, fluid velocity is proportional to the square root of power per unit volume in turbulent conditions (i.e., when Re > 10,000) (5, 6). As a result, an increase in power-per-unit volume would be required to achieve similar mixing times at significantly larger scales. The system average mixing times for the Mobius CellReady bioreactor process containers, as determined by the multipleprobe experimental methods described above, do not dramatically increase with increasing power per unit volume across the agitation range tested. The 50-L and 200-L bioreactor process containers contain a single baffle, which coupled with the off-center, angled position of the bottom mounted impeller, provides good mixing dynamics even at lower power inputs. Empirical results show the mixing time to be 12–13 s from 2 to 15 W/m3 for the 3-L, 38–24 s from 5 to 30 W/m3 for the 50-L and 33–26 s from 1 to 25 W/m3 for the 200-L bioreactor process containers as displayed in Figure 3.


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