Frustoconical Bioreactor with Gas Sparging to Reduce Shear Stress
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Solution Overview
Problem
Current bioreactors face challenges in maintaining optimal conditions for cell culture, including shear stress, high maintenance and operating costs, and issues with galvanic and polarographic sensors, which affect the efficiency and quality of cell cultivation and product production.
Innovation Solution
A bioreactor design featuring a frustoconical internal cavity with angled cross-sections, disposable sensors, and a system comprising an upper and lower tank with a filter membrane, stirring mechanism, and ultrasonic shaker, along with a method for culturing immune cells that includes seeding, activating, transducing, and harvesting, to optimize cell growth and minimize shear stress and maintenance costs.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If mechanical or chemical processes are employed to control dissolved oxygen and carbon dioxide levels in a bioreactor, then DO and CO2 levels can be maintained within predetermined ranges, but excessive shear stress is applied to the cells being cultured, which negatively affects cell culture yield
Solution Approach 1:
The patent replaces traditional mechanical agitation systems with a gas sparging system that introduces gas bubbles through a porous plate or tube at the bottom of the bioreactor. This substitution eliminates the mechanical shear stress caused by impellers while maintaining effective gas-liquid mass transfer for DO and CO2 control through bubble formation and rising motion
Solution Approach 2:
The patent employs pneumatic principles by using gas flow through a porous distribution system to create bubbles that provide both oxygenation and mixing. The gas flow rate and bubble characteristics are controlled to achieve adequate mass transfer without creating excessive hydrodynamic shear stress on the cultured cells
2Productivity
If reusable bioreactors are used, then they can be employed for multiple cell culture runs, but they suffer from excess maintenance and operating costs and problematic galvanic and polarographic sensors
Solution Approach 1:
The patent employs disposable single-use bioreactors that are discarded after one use, eliminating the need for complex cleaning, sterilization, and maintenance procedures associated with reusable systems. The disposable nature reduces operating costs and eliminates sensor contamination issues while maintaining productivity through a portfolio of single-use devices with different capacities
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 design provides improved control over cell culture conditions, reduces maintenance and operating costs, and enhances the production of high-quality cells such as CAR T cells, while eliminating the need for problematic sensors, thereby increasing yield and reducing the risk of contamination.
Implementation Method 1
a filter membrane disposed such that liquid flowing from the upper tank to the lower tank mast pass therethrough
Implementation Method 2
an ultrasonic shaker disposed adjacent the filter
Data Source
AI summary
A bioreactor is provided, comprising a housing extending along a vertical axis and defining an internal cavity therewithin, top and bottom covers at opposite ends of the housing, and a plurality of ports, each configured to facilitate fluid communication between the internal cavity and the exterior of the bioreactor. The internal cavity has a frustoconical shape, the frustoconical shape being formed such that horizontal cross-sections are coaxial about a line which is angled with respect to the vertical axis.