Rotating Mesh Spinfilter for Stem Cell Medium Exchange
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Solution Overview
Problem
Current methods for medium exchange in suspension cultures of stem cells, such as those used in bioreactors, often result in cell loss, stress, and differentiation due to sedimentation or centrifugation, which are not suitable for large-scale or GMP-controlled applications.
Innovation Solution
The use of a rotating mesh, such as a spinfilter, for perfusion-based medium exchange that allows continuous retention of stem cell aggregates within the culture vessel, minimizing mechanical stress and maintaining optimal growth conditions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If repeated batch feeding strategy is used for medium exchange in suspension culture, then medium exchange can be performed, but cell aggregates settle to the bottom causing fusion and spontaneous differentiation
Solution Approach 1:
The system dynamically switches between two operational modes: a first mode where the substrate rotates at a first speed to retain cell aggregates on its surface during medium exchange, and a second mode where the substrate rotates at a second speed to release the cell aggregates. This dynamic speed adjustment allows the same substrate to perform both cell retention and cell release functions, resolving the contradiction between performing medium exchange and maintaining cell aggregate stability
2Ease of operation
If agitation is stopped for medium exchange, then spent medium can be removed, but cell aggregates settle and fuse together
Solution Approach 1:
Instead of stopping agitation, the system maintains rotation but changes the rotational speed to a first speed that creates centrifugal force to retain cell aggregates on the substrate surface. This allows continuous agitation while preventing settlement and fusion, resolving the contradiction between medium removal and preventing aggregate fusion
Solution Approach 2:
The rotating substrate acts as an intermediary between the cell aggregates and the medium exchange process. By controlling the rotation speed, the substrate mediates the interaction between centrifugal force (preventing settlement) and medium flow (enabling exchange), allowing both medium removal and prevention of aggregate fusion to occur simultaneously
3Productivity
If large volume of medium is exchanged, then nutrient replenishment is effective, but culture parameters change suddenly causing cell stress
Solution Approach 1:
The system enables continuous medium exchange by maintaining substrate rotation at a first speed during the entire exchange process. This continuous rotation prevents cell settlement while allowing gradual replacement of spent medium with fresh medium, avoiding sudden changes in culture parameters and reducing cell stress, thus resolving the contradiction between effective nutrient replenishment and minimizing cell stress
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This method enables efficient and automated medium exchange without disturbing the stem cells, maintaining their viability and pluripotency, and supports higher yields and quality of stem cells by providing a stable culture environment.
Implementation Method 1
The use of a rotating mesh, such as a spinfilter, for perfusion-based medium exchange
Data Source
AI summary
The present invention relates to a method of expanding stem cells cultured as cell aggregates in a suspension culture changing culture medium and a method of medium exchange for the same cells characterized in the use of a rotating mesh such as a spinfilter device. The present invention further relates to a use of a rotating mesh for medium exchange in a suspension culture of stem cells.