Fixed-Bed Bioreactor Porous Disk Substrate for Uniform Cell Distribution
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Solution Overview
Problem
Current cell culture bioreactors face challenges such as non-uniform cell distribution, channeling effects, and inefficient cell harvesting, particularly in packed bed systems, which hinder large-scale production and productivity.
Innovation Solution
A fixed-bed bioreactor system with a cell culture substrate comprising a plurality of porous disks in a stacked arrangement, which allows for uniform cell distribution, efficient media perfusion, and easy cell harvesting, while maintaining structural support and mechanical stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If packed bed bioreactor systems with porous particles or non-woven microfibers are used, then high cell density can be achieved, but non-uniform cell distribution and channeling effects occur
Solution Approach 1:
The bioreactor is divided into multiple zones with different flow rates. The flow distribution system segments the incoming medium into multiple streams that are distributed uniformly across the packed bed cross-section, preventing channeling effects and ensuring uniform cell distribution while maintaining high cell density.
Solution Approach 2:
Different regions of the packed bed are provided with optimized local properties through the flow distribution system. Each local region receives appropriate flow rates and nutrient supply tailored to its specific needs, ensuring uniform cell distribution and preventing the channeling effects that occur in homogeneous systems.
2Quantity of substance
If packed bed bioreactor systems are used, then high cell density can be achieved, but cell harvesting becomes inefficient
Solution Approach 1:
The system enables dynamic operation modes that can be switched between culture and harvesting phases. During harvesting, the flow distribution system can be adjusted to facilitate efficient cell recovery while maintaining the high cell density achieved during the culture phase, thus resolving the contradiction between maintaining high cell density and enabling efficient harvesting.
3Quantity of substance
If hollow fiber bioreactor systems are used to increase volumetric density, then high cell density can be achieved, but cell growth is inhibited by lack of nutrients
Solution Approach 1:
The flow distribution system ensures continuous and uniform supply of nutrients and oxygen throughout the packed bed. By maintaining continuous flow distribution across all regions of the bioreactor, the system prevents nutrient depletion and maintains reliable cell growth performance even at high cell densities, resolving the contradiction between achieving high cell density and maintaining cell growth performance.
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 system achieves high cell density, uniform cell distribution, and efficient harvesting, enhancing bioprocessing productivity and scalability, and enabling the production of high-quality viral vectors and therapeutic proteins.
Implementation Method 1
a plurality of openings formed in the substrate and passing through the thickness of the substrate, wherein the plurality of openings is configured to allow flow of at least one of cell culture media, cells, or cell by-products through the thickness of the substrate
Implementation Method 2
efficient media perfusion
Data Source
AI summary
A fixed-bed bioreactor system is provided that includes a vessel with a media inlet, a media outlet, and an interior cavity disposed between and in fluid communication with the media inlet and media outlet. The vessel further includes a cell culture substrate disposed in the interior cavity between the media inlet and the media outlet in a packed-bed configuration, the cell culture substrate including a plurality of porous disks in a stacked arrangement. The interior cavity includes a cell culture section and a spacer section, the cell culture substrate defining the cell culture section and the spacer section being disposed between the cell culture section and the media outlet, and each of the plurality of porous disks has a surface configured to culture cells thereon.