Acoustic Standing Wave Bioreactor for Cell Retention
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Solution Overview
Problem
Perfusion bioreactors face operational issues due to complex cell retention systems, which can malfunction or fail, limiting their attractiveness and efficiency in producing high cell densities and biomolecules like recombinant proteins and monoclonal antibodies.
Innovation Solution
A bioreactor system incorporating a filtering device with ultrasonic transducers and reflectors to create multi-dimensional acoustic standing waves, allowing for efficient cell retention and separation of biomolecules without the need for high-energy centrifuges, using acoustophoresis to trap cells and biomolecules, thereby reducing costs and maintaining flux rates.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If a perfusion bioreactor uses a cell retention device to prevent escape of culture, then cell density and productivity are improved, but device complexity and risk of malfunction increase
Solution Approach 1:
The patent replaces mechanical cell retention devices (such as filters, centrifuges, or membranes) with an acoustic field-based retention system. Ultrasonic transducers generate acoustic standing waves that create acoustic radiation pressure to trap cells in specific regions of the bioreactor, eliminating the need for complex mechanical retention equipment while maintaining high cell densities
Solution Approach 2:
The patent introduces an acoustic field as an intermediary between the cells and the retention mechanism. The acoustic standing waves create regions of high and low pressure that act as a mediating force to confine cells without direct mechanical contact, thereby simplifying the overall system architecture
2Ease of operation
If a fed-batch bioreactor is used for simplicity, then ease of operation is improved, but productivity and volume requirements worsen
Solution Approach 1:
The patent implements a dynamic retention system where acoustic standing waves can be activated, deactivated, or adjusted in real-time based on process needs. This allows the system to transition between different operational modes (retention and non-retention) without mechanical intervention, providing operational flexibility while maintaining high productivity
Solution Approach 2:
The acoustic field system serves multiple functions simultaneously: cell retention, mixing, and process control. The same acoustic standing wave mechanism that retains cells can also be used to monitor cell distribution and adjust flow rates, making the system more versatile and efficient compared to traditional fed-batch 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
The system achieves high cell retention and separation efficiencies, reducing cross-contamination risks and operational costs, enabling continuous production of biomolecules with lower capital and start-up expenses, and minimizing cell loss, while maintaining high product concentrations and yields.
Implementation Method 1
at least one ultrasonic transducer and a reflector located opposite the at least one ultrasonic transducer, the at least one ultrasonic transducer being driven to produce a multi-dimensional standing wave in the flow chamber
Implementation Method 2
using acoustophoresis to trap cells and biomolecules
Data Source
AI summary
A perfusion bioreactor includes at least one ultrasonic transducer that can acoustically generate a multi-dimensional standing wave. The standing wave can be used to retain cells in the bioreactor, and can also be utilized to dewater or further harvest product from the waste materials produced in a bioreactor.