Upstream Processing
Nov 10, 2022
| 4 min read

Rocking Motion vs. Stirred Tank Bioreactors - Which Technology is Best Suited For My Cells?

Selecting the right cell culture technologies is an essential part of process development. Stirred tank and rocking motion bioreactors each offer unique advantages across different applications. Learn what parameters you should consider for your bioprocess.

This article is posted on our Science Snippets Blog

In upstream bioprocesses, the cell line properties, metabolism, and activity; process parameters; and media components work together to influence the productivity and quality of the product. Finding the best bioreactor technology and optimal conditions for your cell line could require significant parameter control to maximize productivity and cell viability.  

Two leading technology types for bioreactor cell cultures are rocking motion and stirred tank bioreactors.

Rocking Motion Bioreactors

A rocking motion bioreactor is based on wave-mixed technology for mixing and oxygen transfer in suspension cell cultures. An inflated 2D single-use bag is attached to a motorized platform that creates a rocking motion to induce waves in media, keeping the cells in suspension and aerating the culture.  

Stirred Tank Bioreactors

A stirred tank bioreactor commonly consists of a tubular vessel design with a defined height-to-diameter dimension ratio. Mixing is achieved through a central stirrer element inside the culture vessel, leading to an optimal distribution of nutrients and gasses inside the vessel. The stirred tank design has long been the gold standard for stainless steel bioreactors and is still implemented for most single-use bioreactor systems.

What Should You Consider When Choosing Between Technologies?

Below are some questions to consider when selecting your bioreactor technology and some recommendations to help you make your choice.

Is Your Cell Line | Product Shear Sensitive?

Both rocking motion and stirred tank technologies are suitable for a range of cells, including CHO, HEK293, stem cells, and CAR-T cells. Since rocking motion bioreactors do not use submerged gassing or stirrer elements, they provide a gentle environment for all cell types. This is especially useful for shear-sensitive cells, such as endothelial cells, and unstable products, such as bioconjugates.

Do You Require Large Culture Volumes?

Rocking motion technology is suitable for working volumes of 0.1 L-100 L while stirring motion single-use technologies are suitable for up to 2,000 L. Stirred tank bioreactors are well known for excellent scalability, as constant geometry parameters enable simplified design space transfer even for demanding processes. Consequently, this results in reduced time and effort for process development.  

Are You Implementing Process Intensification Strategies?

Rocking motion perfusion bags are well suited to simplify process intensification using an integrated cell retention device. Rocking motion technology can be integrated as part of a seed train process to ensure maximum cell culture viability and high-density inoculation of the production bioreactor (Figure 1). This strategy can reduce production bioreactor culture days by up to 20%.

A series of bioreactors are required for process development and production seed trains. This can include a mix of multi-parallel single-use bioreactors, rocking motion, and commercial-scale stirred tank reactors. 

Figure 1 During production, the Biostat® RM can be integrated into a seed train to support a seamless transition to large-scale culture in the Biostat STR®    

  • The Ambr® range of small-scale, multi-parallel bioreactors is fully scalable up to the Biostat® range, making them ideal for process development. During production, the Biostat® RM can be integrated into a seed train and supports a seamless transition to large-scale culture in the Biostat STR®   

Are You Exploring Single-Use Applications?

Single-use bioreactors are increasingly being adopted in biopharmaceutical manufacturing owing to their relative ease of use, cost-savings, and positive impact on both facility flexibility and process robustness. Both rocking motion and stirred tank bioreactor technologies are compatible with single-use culture vessels.

  • The range of scalable Flexsafe® Single-Use Bags supports high-performing and reproducible growth from process development to production and even across bioreactor technologies using just one film.   

Regardless of Your Choice – Insist on Process Control

Regardless of the cell culture technology selected, process monitoring and control are essential to maximizing the quality and consistency of cell cultures and final products. The outstanding control offered by process analytical technologies (PATs), such as the  BioPAT® range of sensors and analyzers, provide real-time data to promote high-quality production and optimal compliance.  

  • Both rocking motion and stirred tank technologies can be used with precision as long as the cultivation parameters are measured and controlled by PATs like BioPAT® Viamass, BioPAT® Trace, and the Biobrain® automation platform, which allows process streamlining.

Key Takeaway

The stirred tank design has long been the gold standard for stainless steel bioreactors and is still followed for most single-use bioreactor systems. However, wave-mixing (or rocking motion) technology can be a good alternative for shear-stress-sensitive cell lines and make an excellent addition to a productive, intensified seed train.

Consider and weigh the above factors before deciding which technology to implement into your process.

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