Rotating Bioreactor with Movable Wall for Continuous Media Exchange
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Solution Overview
Problem
Bioreactors for cell cultures and tissues face challenges in maintaining uniform spheroids under omnidirectional normogravity conditions, leading to suboptimal growth due to frequent rotation stops for media changes, which causes mechanical stress and uneven nutrient distribution.
Innovation Solution
A bioreactor design with a movable wall separating fresh and spent media chambers, allowing for continuous rotation and media exchange without stopping, using a piston-driven system for media flow and optional membrane for spheroid containment, enabling uniform spheroid growth and reduced mechanical stress.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If the bioreactor stops rotation for media changes, then media exchange can be performed, but spheroid uniformity deteriorates and mechanical stress increases
Solution Approach 1:
The bioreactor system enables continuous rotation during media exchange operations. The media delivery system introduces fresh media through ports while the rotor continues rotating, eliminating the need to stop rotation for media changes and maintaining continuous uniform mixing of spheroids.
Solution Approach 2:
A media delivery system with dedicated ports and tubing acts as an intermediary to introduce fresh media into the rotating bioreactor without requiring rotation to stop. The system uses gravity-driven flow and controlled dispensing to deliver media during continuous operation.
2Ease of operation
If the bioreactor stops rotation for media changes, then media exchange can be performed, but nutrient distribution deteriorates
Solution Approach 1:
Continuous rotation during media exchange ensures that spheroids remain in constant motion and uniformly distributed throughout the media. This prevents sedimentation and ensures all spheroids receive equal access to nutrients and oxygen during the media exchange process.
3Stability of the object's composition
If rotation speed is increased to prevent spheroid settling, then spheroid uniformity improves, but mechanical shear stress increases
Solution Approach 1:
The bioreactor system dynamically adjusts rotation speed based on operational requirements. During normal operation, a low rotation speed (0.5-5 rpm) maintains spheroid uniformity with minimal shear stress. During media exchange, the system continues rotating at this low speed while introducing media flow to prevent settling, avoiding the need for high-speed rotation that would cause excessive shear stress.
4Ease of operation
If rotation is stopped frequently for media changes, then media exchange is simplified, but productivity deteriorates
Solution Approach 1:
The automated media delivery system enables media exchange without stopping rotation, maintaining continuous culture growth conditions. This eliminates the productivity losses associated with frequent start-stop operations and maintains optimal metabolic conditions for spheroid development throughout the culture period.
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
The bioreactor maintains uniform spheroids with reduced mechanical stress, improving metabolic performance and enabling more reliable in vitro toxicological evaluations by minimizing rotation stops and ensuring consistent nutrient supply.
Implementation Method 1
The movable wall is connected to a piston, for moving the movable wall back and forth to pass the fresh media from the fresh media chamber to the cell culture chamber and from the cell culture chamber to the spent media chamber
Implementation Method 2
continuous rotation of a compartment of the bioreactor containing the cell culture or tissue using a clinostat type device... preventing the cells to adhere to the compartment walls... the rotation infinitesimally increases the gravitational force (centripetal acceleration)
Implementation Method 3
Stopping the rotation is normally needed in order to change the media or add compounds... during the stop of the rotation, the spheroids may settle down to the bottom or adhere to the walls of the compartment. This results in turn in a reduction in the availability of gasses, e.g. oxygen, and nutrients to the spheroids
Data Source
AI summary
The invention relates to a bioreactor (10, 10′, 100) adapted for rotation, the bioreactor comprising: a vessel (12) comprising: a first end (24) and a second end (26) which define a central axis (28) of the vessel (12) extending along a first direction, e.g. a length direction, of the vessel (12) from said first (24) to said second end (26), at least one wall (18, 18′, 20) running along the first direction of the vessel (12), at least one media conduit (22, 22′) defining a volume for receiving fresh or spent media; an inner chamber defined by at least a part of a space confined within said at least one wall (18, 18′, 20) and comprising a fresh media chamber (14) and a spent media chamber (16); a cell culture chamber (30) in fluid communication with said at least one media conduit (22, 22′) and said fresh (14) and/or spent media chamber (16); and a movable wall (38) configured, within said inner chamber, to separate said fresh media chamber (14) from said spent media chamber (16) within said inner chamber.