Automated Suspension Cell Medium Exchange via Gravity Settling
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Solution Overview
Problem
Current methods for changing culture medium in suspension cultures face challenges, particularly in scalable and automated processes, as they often require removing cells from the system, leading to mechanical stress and loss of pluripotency in stem cells.
Innovation Solution
A method involving transferring a fraction of the suspension culture into a container with a bottom opening, allowing cells to settle by gravity, and then dispensing them back into the culture medium while discarding the supernatant, allowing for continuous medium exchange without stopping the stirrer and minimizing mechanical stress.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If cells are removed from the suspension culture system for medium exchange, then medium change can be performed, but mechanical stress is applied to cells and pluripotency is lost
Solution Approach 1:
The invention extracts only the necessary component (spend medium) from the suspension culture system while leaving the cells intact. By using a filter element that retains cells within the bioreactor, the system removes only the medium portion for replacement, avoiding the need to remove and reintroduce cells which would cause mechanical stress and pluripotency loss
2Ease of operation
If stirring is interrupted to allow sedimentation for medium exchange, then medium can be removed and replaced, but aggregate fusion occurs and pluripotency decreases
Solution Approach 1:
The invention maintains continuous stirring action throughout the medium exchange process. The filter element enables medium removal and replacement without interrupting the stirring, thereby preventing aggregate fusion and maintaining the homogeneity and pluripotency of cell aggregates throughout the bioprocess
3Reliability
If cells are retained during medium exchange, then cell viability is maintained, but the process becomes complex and less scalable
Solution Approach 1:
The invention introduces a filter element as an intermediary component that enables cell retention during medium exchange. This filter acts as a mediator between the stirring mechanism and medium removal system, allowing automated scalable processes to retain cells without requiring complex manual intervention or disrupting cell culture conditions
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 maintains cell viability and pluripotency, achieving efficient and scalable medium exchange with reduced manual intervention and stress on cells, as demonstrated by increased growth rates and pluripotency marker expression in induced pluripotent stem cells.
Implementation Method 1
allowing the cells comprised in the fraction of the suspension to settle at the at least one opening at the bottom of the container by gravitation, thereby forming a supernatant
Data Source
AI summary
The present invention relates to a method of changing culture medium of a suspension culture, the suspension culture comprising cells suspended in the culture medium, the method comprising: (i) transferring a fraction of the suspension culture into a container, wherein the container comprises at least one opening at the bottom; (ii) allowing the cells comprised in the fraction of the suspension to settle at the at least one opening at the bottom of the container by gravitation, thereby forming a supernatant; (iii) dispensing the cells settled at the bottom of the container (back) into the suspension culture; (iv) discarding the supernatant.