Don't let the cutting destroy the cells! Teach you how to choose the appropriate mixing system to achieve high yield and live cell dual standards!
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- Issue Time
- Aug 4,2025
Summary
In biopharmaceuticals and cell culture
In biopharmaceuticals and cell culture, there is a key issue: in order to mix nutrients evenly and transfer oxygen, stirring is necessary, which can generate shear forces.
And many cells, such as mammalian cells, plant cells, etc., are sensitive to shear forces. Excessive shear forces can lead to cell rupture and reduced activity, directly affecting the yield and quality of products.
So, the key to designing a bioreactor is to solve this problem through reasonable technical methods, while ensuring mixing and mass transfer effects, and controlling the shear force within the range that cells can withstand.
1、 Stirring system: The key to regulating shear force is the stirring blade, which is the main component driving fluid movement in the reactor. Its design directly affects the distribution and magnitude of shear force.
Different types of impellers exhibit varying performance in balancing shear forces and mixing efficiency due to their different fluid dynamics characteristics.
1. Radial flow impeller: Suitable for high shear scenarios. Its blade design allows the fluid to be quickly ejected radially, creating strong local turbulence, energy concentration, and high shear forces.
The advantage of this impeller is that it can efficiently crush bubbles and improve oxygen transfer efficiency, making it suitable for high viscosity media or microbial cultivation with high oxygen demand, such as bacterial fermentation.
But the rotational speed must be strictly controlled. In plant cell culture, when the tip speed of the turbine exceeds 0.5m/s, the cell survival rate will significantly decrease, so it is only suitable for cells that can withstand higher shear forces.
2. Axial flow impeller: achieving low shear mixing
Axial flow impellers such as upward suction inclined blade turbines guide fluid circulation along the axial direction through the inclination angle of the blades, reducing the intensity of local turbulence and achieving uniform mixing in low shear environments.
Simulations have shown that this type of impeller can evenly disperse gas at low speeds, avoiding excessive energy concentration. It is particularly suitable for high-density cell culture, such as producing monoclonal antibodies using CHO cell culture.
Its design concept is to ensure the stability of the cell survival environment by expanding the mixing range, reducing local flow velocity, and sacrificing instantaneous efficiency to a certain extent.
3. Advantages of centrifugal impeller reactor
A new breakthrough has been made in the centrifugal impeller bioreactor (CIB), which is based on the principle of centrifugal pump and drives fluid circulation through central negative pressure, ensuring overall mixing efficiency while greatly reducing local shear forces.
In practical applications of high-density cultivation, the oxygen transfer capacity of CIB has been improved by 30% compared to traditional impellers, while cell activity can still be maintained at over 90%. This indicates that this innovative structure is significantly effective in balancing "high efficiency" and "low shear".
二、 Ventilation Strategy: Balancing Bubble Shear and Mass Transfer
In addition to stirring, the generation and rupture of bubbles during ventilation are also important causes of shear force.
Aerobic cell culture requires continuous oxygen supply, but the instantaneous impact force when bubbles burst may cause fatal damage to animal cells without cell walls.
Therefore, the design of ventilation strategies should find a suitable balance between "sufficient oxygen supply" and "reducing damage".
In traditional bubble ventilation, small bubbles with a diameter less than 3mm can improve oxygen transfer efficiency due to their large surface area. However, when they rupture, the local shear force can reach 10 ⁴ W/m ³, which is enough to damage animal cells.
There are mature optimization methods in the industry to address this issue: firstly, using large bubbles with a diameter of 10-20mm to reduce shear damage by lowering the frequency of rupture; The second method is to add Pluronic F68 and other shear protectants, which utilize their surface activity to prevent direct contact between cells and bubbles.
The combination of these two methods can increase cell survival rate by more than 40%.
2. Bubble free ventilation: Safety first membrane ventilation (such as hollow fiber membranes) and surface ventilation provide oxygen through gas diffusion or liquid exchange, completely avoiding the risk of shear caused by bubble rupture. They are particularly suitable for cells that are extremely sensitive to shear forces, such as stem cells.
However, this type of method has low mass transfer efficiency and usually requires low-speed stirring to enhance fluid circulation and compensate for the lack of oxygen transfer, making it more suitable for small-scale, high value-added cell culture.
3. Airlift reactor: The choice for extremely low shear is the Airlift reactor (ALR), which does not require mechanical stirring and relies on the density difference formed by the introduction of gas to drive fluid circulation, minimizing shear forces.
Its main advantage is that it is suitable for the cultivation of ultra sensitive systems, such as microalgae and insect cells. However, due to the dependence on poor gas density for circulation dynamics, its mixing ability is weak in high viscosity media, making it more suitable for low viscosity and low shear force requirements cultivation scenarios.
