Acoustic Standing Wave Bioreactor for High-Density Cell Retention
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Solution Overview
Problem
Perfusion bioreactors face operational issues due to complex cell retention systems, which limit their attractiveness despite offering higher cell densities and lower capital costs compared to fed-batch processes.
Innovation Solution
A bioreactor system incorporating a filtering device with a multi-dimensional standing wave generated by ultrasonic transducers, which traps cells and separates biomolecules from the cell culture media, reducing cross-contamination and operational complexity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If a perfusion bioreactor uses a cell retention device to prevent escape of culture, then cell density can be maintained at high levels (30-100 million cells/mL), but the device complexity increases and operational reliability decreases due to potential malfunction or failure
Solution Approach 1:
The patent replaces mechanical cell retention devices with an acoustic field-based separation 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 filtration or centrifugal separation systems while maintaining high cell density
Solution Approach 2:
The patent introduces an acoustic field as an intermediary between the cell culture and the separation function. The acoustic standing waves create a visible trap region that mediates cell retention without direct mechanical contact, allowing cells to be confined through acoustic pressure rather than physical barriers
2Ease of operation
If a fed-batch bioreactor is used with gradual addition of fresh nutrients, then the process is simple and carries over from fermentation processes, but start-up costs are high and large volume is required to obtain cost-effective product
Solution Approach 1:
The patent implements continuous perfusion culture where fresh media is continuously added and spent media is continuously removed, maintaining optimal nutrient levels and removing waste products throughout the process. This continuous operation eliminates the non-productive downtime associated with batch processing and enables smaller reactor volumes to achieve cost-effective production
3Productivity
If a perfusion bioreactor operates continuously with fresh media feed, then nonproductive downtime is reduced or eliminated and cell density is maintained at high levels, but operational reliability decreases due to complexity of cell retention equipment management
Solution Approach 1:
The patent replaces complex mechanical cell retention equipment with an acoustic field-based system that uses ultrasonic transducers to create standing waves. This substitution eliminates mechanical moving parts and filtration systems that are prone to failure, while maintaining the ability to operate continuously at high cell densities
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 efficient separation of biomolecules, reducing the need for high-energy centrifuges and minimizing cross-contamination, while maintaining high flux rates and lowering energy costs.
Implementation Method 1
the at least one ultrasonic transducer being driven to produce a multi-dimensional standing wave in the flow chamber
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.