Bioreactor Rotation for Uniform Cell Distribution
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Solution Overview
Problem
Cell expansion systems with stationary bioreactors are limited in cell production due to the influence of gravity during cell loading and distribution, which impedes the expansion process.
Innovation Solution
A method involving the rotation and orientation manipulation of the bioreactor to mitigate the effect of gravity, including specific angular velocities and pause times to achieve a net impulse of zero on cells, facilitating uniform cell distribution and expansion.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If the bioreactor is kept stationary during cell loading, then the structure is simple and easy to operate, but gravity impedes cell distribution and expansion
Solution Approach 1:
The bioreactor is transformed from a stationary structure to a dynamic one capable of rotation around its longitudinal axis. The system includes a rotation mechanism that can rotate the bioreactor at controlled angular velocities (e.g., 1-10 rpm) to distribute cells uniformly throughout the bioreactor volume, preventing gravity-induced settling and improving cell expansion efficiency.
Solution Approach 2:
The bioreactor implements periodic rotation cycles during cell loading and expansion phases. The rotation is activated during cell loading to ensure uniform distribution, then can be paused or slowed during specific cultivation phases, creating a periodic action pattern that optimizes both cell distribution and growth conditions.
2Productivity
If the bioreactor is rotated during cell loading, then cell distribution is improved, but the device complexity increases
Solution Approach 1:
The rotation mechanism serves multiple functions: it distributes cells during loading, prevents settling during expansion, and can be used for harvesting. This multi-functionality justifies the added complexity by eliminating the need for separate distribution and harvesting mechanisms.
Solution Approach 2:
The bioreactor's own structure is utilized for rotation, with the longitudinal axis serving as the rotation axis. The system uses its structural components (support framework, drive mechanism integrated into the base) to enable rotation, rather than requiring entirely external positioning systems.
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 approach enhances cell distribution and expansion by minimizing the impact of gravity, leading to improved cell production and growth efficiency in bioreactors.
Implementation Method 1
The influence of gravity may impede the distribution of cells when first introducing the cells into the bioreactor
Data Source
AI summary
A method of distributing a plurality of cells in a bioreactor of a cell expansion system includes manipulating an orientation of the bioreactor such that a net impulse due to gravity acting on the plurality cells in the bioreactor is reduced. One method includes (a) rotating the bioreactor at an angular velocity ω about an axis of rotation and through an angular displacement θ, the bioreactor rotating from a first orientation to a second orientation; (b) holding the bioreactor still at the second orientation for a first period of time t1, wherein t1 substantially equals 2/ω; (c) rotating the bioreactor at the angular velocity ω about the axis of rotation and through the angular displacement θ; and (d) holding the bioreactor still for a second period of time t2, wherein t2 substantially equals t1.