Suspended Bioreactor Modules for High-Density Virus Propagation
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Solution Overview
Problem
Current bioreactor designs face challenges in achieving maximum cell density and viability for virus production due to inadequate oxygenation, shear forces, and hydrostatic pressures, while also requiring efficient nutrient supply and waste removal, and lack a comprehensive system for safe handling and inactivation of bio-safety level viruses.
Innovation Solution
A closed, modular system with incubation vessels, media tanks, and controlled flow systems that minimize stress on cells, provide consistent nutrient supply, and enable efficient virus collection and inactivation, using enzymatic degradation of cellular DNA and ion exchange columns for virus separation and inactivation, with scalable and safe handling of bio-safety level viruses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If conventional bioreactor designs are used for virus production, then cell culture can be maintained, but cell density and viability are limited due to inadequate oxygenation, shear forces, and hydrostatic pressures
Solution Approach 1:
The bioreactor system is divided into multiple suspended bioreactor modules (101-106) that can be independently operated. Each module contains cells attached to removable matrixes (111-116), allowing segmentation of the cell culture system. This segmentation enables better distribution of oxygen and nutrients while reducing the harmful effects of shear forces and hydrostatic pressures on any single cell population.
Solution Approach 2:
The patent transitions from traditional fixed-bed or stirred-tank configurations to a suspended module system where bioreactor modules float or are suspended in the culture medium. This dimensional change allows cells to be distributed throughout the volume rather than confined to the bottom, improving oxygenation and reducing hydrostatic pressure effects while maintaining high cell density.
2Quantity of substance
If conventional bioreactor designs are used, then cell culture can proceed, but nutrient supply and waste removal are insufficient for maximum cell density
Solution Approach 1:
The system implements continuous circulation of culture medium through the suspended bioreactor modules, ensuring constant supply of nutrients and oxygen to all cell populations. The modular design allows for continuous operation where cells are constantly exposed to fresh medium, maximizing nutrient utilization and waste removal efficiency for achieving maximum cell density.
3Productivity
If virus production is scaled up, then bulk quantities can be produced, but safe handling and inactivation of bio-safety level viruses becomes more difficult
Solution Approach 1:
The system extracts or separates the virus production process into contained bioreactor modules that can be individually handled. The removable matrixes allow for easy extraction of infected cells for virus harvest while minimizing exposure to live viruses. This modular extraction approach enables scaling up virus production while maintaining worker safety through reduced exposure.
Solution Approach 2:
The patent introduces intermediate containment structures (bioreactor modules with removable matrixes) that serve as mediators between the live virus production environment and the worker environment. These intermediaries allow for safe transfer and handling of viral materials through controlled access points, enabling bulk virus production while protecting workers from direct exposure to hazardous viruses.
4Productivity
If traditional cell culture methods are used, then cells can be grown, but the system lacks integration for efficient virus collection, DNA elimination, and inactivation
Solution Approach 1:
The patent merges multiple functions (cell culture, virus propagation, virus harvest, DNA elimination, and inactivation) into an integrated bioreactor system. The suspended modules combine cell attachment matrices with built-in harvesting mechanisms, and the system incorporates DNAse treatment and inactivation steps within the same workflow. This merging reduces overall system complexity while maximizing virus yield through streamlined operations.
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 system allows for higher cell density and viability, increased virus yield, and safe handling of hazardous viruses, achieving efficient production and inactivation while minimizing stress and ensuring worker safety, with the ability to handle various bio-safety levels.
Implementation Method 1
the column comprises hydrophobic ion exchange material that specifically binds the live virus
Implementation Method 2
providing a DNAse or suitable enzyme to degrade the cellular DNA prior to purification
Implementation Method 3
eluting the virus from the column with a high salt solution
Data Source
AI summary
The present invention provides a closed system to propagate virus-infected cells without the effect of shear force, while providing quicker access to nutrients than is available conventionally. This system design allows for a high density of infected cell growth to increase the virus yields and to maintain homogeneity of the contents of the main container. The system further provides a nuclease to degrade the cellular DNA prior for purification of the virus or viral components. As the system is designed for maximum containment at low risk, the live virus can be a hazardous virus such as a Bio-safety Level 3 (BSL 3), BSL 4 or BSL5 virus.