Bioreactor Fiber Scaffold Circulation for Cell Culture
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Solution Overview
Problem
Current bioreactors face challenges in ease of use, automation, and reproducibility, particularly in cultivating large numbers of cells such as stem cells, with limitations in nutrient diffusion, cell separation distances, and shear stress management.
Innovation Solution
A bioreactor design featuring a reservoir container, duct with fiber assemblies, and a circulation system that includes a manifold assembly and screen holder with grooves and slots for supporting fiber scaffolds, ensuring controlled flow and minimal shear stress, along with a method for seeding and harvesting cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If conventional bioreactor designs are used, then cell culture is possible, but ease of use and automation are limited
Solution Approach 1:
The bioreactor is divided into modular components including a reservoir container, duct system, fiber assemblies, and circulation system. Each component can be independently assembled, cleaned, and replaced, significantly improving ease of operation while maintaining overall system functionality.
Solution Approach 2:
The circulation system serves multiple functions: it delivers nutrients to cells, removes waste products, controls shear stress, and enables automation. This multi-functionality reduces the number of separate systems needed, improving ease of use without proportionally increasing complexity.
2Reliability
If conventional bioreactor designs are used, then cell culture is possible, but reproducibility is limited
Solution Approach 1:
The standardized modular components with defined interfaces ensure consistent assembly and operation across multiple bioreactors. The fiber assemblies with controlled porosity and the standardized circulation system create reproducible flow conditions and shear stress profiles, enhancing reliability.
3Productivity
If large numbers of cells are cultured, then productivity increases, but nutrient diffusion and shear stress management become challenging
Solution Approach 1:
The fiber assemblies provide locally optimized structures with controlled porosity and surface properties that promote cell attachment and growth. The circulation system delivers nutrients locally to high-density cell regions while maintaining shear stress within acceptable ranges through controlled flow parameters.
Solution Approach 2:
The circulation system dynamically adjusts flow rate and other parameters to maintain optimal shear stress levels as cell density increases. This allows the bioreactor to scale up cell production while preventing shear stress from becoming harmful to the cells.
4Productivity
If large numbers of cells are cultured, then productivity increases, but nutrient diffusion becomes limited
Solution Approach 1:
The fiber assemblies create a three-dimensional structure with controlled porosity that enhances nutrient diffusion throughout the cell population. The circulation system supplements this by actively transporting nutrients to regions with high cell density, ensuring adequate nutrient supply as productivity increases.
Solution Approach 2:
The circulation system uses hydraulic flow to actively transport nutrients through the bioreactor, overcoming diffusion limitations in high-density cell cultures. The controlled fluid circulation ensures adequate nutrient delivery to support large-scale cell production.
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 effectively cultivates large numbers of cells by maintaining optimal nutrient diffusion and minimizing shear stress, enhancing cell growth and reproducibility while facilitating easy operation and automation.
Implementation Method 1
a circulation system for causing the liquid medium to flow upwardly through the duct past or through the plurality of fiber assemblies
Implementation Method 2
the liquid medium flows over the overflow wall within the pocket region
Implementation Method 3
the liquid medium overflows into the moat and is removed from the moat by the circulation system
Data Source
AI summary
A bioreactor includes a reservoir container for holding a liquid medium, a duct providing a flowpath in a generally vertical direction upward from the reservoir container, a plurality of fiber assemblies located within the duct, a top of which is higher than a top of the plurality of fiber assemblies, and a circulation system. The upper end of the duct comprises an overflow wall surrounded by a moat, a bottom of which is lower than a top of the overflow wall. The upper end of the duct and moat contact a pocket region that is bounded by a structure that is connected to the duct and that is isolated from fluid communication with an exterior of the pocket region. The liquid medium flows over the overflow wall within the pocket region, contacts gas in the pocket region, overflows into the moat and is removed therefrom by the circulation system.