Bioreactor Mixing with Segmented Zones and Perfusion
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current bioreactor systems face challenges in achieving high cell density growth within small culture volumes while minimizing shear stress and ensuring efficient nutrient and oxygen distribution, which limits productivity and scalability in biopharmaceutical production.
Innovation Solution
A bioreactor system with a horizontally or vertically oriented culture vessel, a support matrix, and a recirculation loop that includes a gas exchange module and fluid pumping means, allowing for bubble-free aeration and efficient mixing without gas sparging, enabling high-density cell growth and easy operation with reduced contamination risks.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional stirred bioreactor technology is used for large-scale cell culture, then scalability is improved, but local shear rates increase and cell damage occurs
Solution Approach 1:
The bioreactor is segmented into multiple functional zones: a separate mixing chamber for aggressive mixing, a culture chamber for gentle cell cultivation, and a perfusion system. This segmentation allows high-shear mixing operations to be isolated from the low-shear cell culture environment, resolving the contradiction between scalability and shear stress reduction.
Solution Approach 2:
A perfusion medium acts as an intermediary, transporting nutrients and metabolites between the mixing chamber and culture chamber. This mediator enables efficient mass transfer without requiring direct high-shear mixing in the cell culture zone, thus maintaining both productivity and cell viability.
2Ease of operation
If fed-batch bioreactors are used for cell culture, then operation simplicity is improved, but culture lifetime is limited and final product titers are reduced
Solution Approach 1:
The system implements continuous perfusion culture where fresh medium is continuously fed and spent medium is continuously removed. This continuous action extends culture lifetime beyond the limitations of batch systems while maintaining operational simplicity through automated flow control and standard bioreactor hardware.
3Productivity
If perfusion bioreactors with continuous culture are used, then culture lifetime and product titers are improved, but mechanical complexity increases
Solution Approach 1:
The mixing and perfusion functions are merged into a single integrated chamber design. The perfusion medium flow path combines mixing and cell culture functions, eliminating the need for separate complex mixing mechanisms in the culture zone and reducing overall mechanical complexity while maintaining high productivity.
4Stability of the object's composition
If cells are cultured in suspension with stirring, then nutrient distribution is improved, but cell concentration per volume is reduced and harvesting complexity increases
Solution Approach 1:
The system transitions from relying solely on volumetric mixing to incorporating surface-area-based mass transfer through the perfusion medium flow over cell-laden substrates. This dimensional change enables high cell concentration at the interface while maintaining nutrient distribution through the perfusion flow, resolving the contradiction between homogeneous nutrient distribution and high cell density.
Data Source
Figure 1(a)~1(b)
Figure 2(a)~2(b)
Figure 3
AI summary
The present invention relates to bioreactor system and method thereof wherein support matrix (2) comprises at last one central shaft and plurality of peripheral shaft being radially surrounds central shaft. Arrays of discs (11) are mounted along the shaft by defining interspatial vicinities between two successive plates. Thus, discs mounted on peripheral shafts are rotated within the interspatial vicinity of discs of central shaft to ensures sufficient mixing and avoid stagnant fluidic zones which is created when discs are mounted closely apart from each other on shafts. Further, plurality of deflector vanes that are axially provided along the length of the central shaft to redirect substantially co-axial direction fluid flow into interior of culture vessel and more specifically towards the central axis. Thus, bioreactor system provides scalable and disposable bioreactor with efficient mixing and homogeneous conditions and thereby supports high density growth and maintenance of cells and other biological material.