Acoustic Perfusion Device for Cell Retention
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Solution Overview
Problem
Perfusion bioreactors face operational issues due to the complexity and potential malfunction of cell retention systems, which limits their attractiveness despite offering higher cell densities and lower contamination rates compared to fed-batch processes.
Innovation Solution
The development of acoustic perfusion devices that utilize multi-dimensional acoustic standing waves generated by piezoelectric transducers to separate biomolecules from cells, allowing continuous recycling of healthy cells back to the bioreactor while harvesting desired products, thereby reducing nonproductive downtime and operational complexity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If cell retention systems are used in perfusion bioreactors to prevent cell escape during continuous operation, then cell densities can be maintained at high levels (30-100 million cells/mL), but the device complexity increases and operational reliability decreases due to potential malfunction
Solution Approach 1:
The patent extracts the cell retention function from complex mechanical systems and implements it using acoustic fields. Acoustic standing waves created by ultrasonic transducers generate acoustic radiation pressure that selectively retains cells at specific locations (nodes or antinodes) while allowing continuous flow of media and removal of byproducts, thereby eliminating the need for complex mechanical cell retention devices
Solution Approach 2:
The patent replaces mechanical cell retention systems (such as filters, membranes, or centrifugal devices) with an acoustic field-based retention mechanism. The acoustic radiation pressure exerted by standing waves creates a non-contact force field that holds cells in place, substituting mechanical complexity with a field-based approach that is easier to control and maintain
2Productivity
If perfusion bioreactors operate continuously with cell retention systems, then productivity increases through continuous product removal, but the operational reliability decreases due to potential system malfunction
Solution Approach 1:
The patent replaces mechanical cell retention systems with acoustic field-based retention, eliminating moving parts and mechanical failure points. The acoustic standing waves are generated by ultrasonic transducers that can be precisely controlled electronically, providing a reliable means of cell retention without the mechanical complexity that leads to malfunction
Solution Approach 2:
The patent employs dynamic control of acoustic fields to maintain cell retention under varying operational conditions. The frequency and amplitude of ultrasonic waves can be adjusted in real-time to optimize cell retention efficiency while maintaining continuous flow conditions, allowing the system to adapt to changing productivity requirements without compromising reliability
3Device complexity
If fed-batch bioreactors are used instead of perfusion systems, then device complexity is reduced, but productivity decreases due to batch operation requirements and nonproductive downtime
Solution Approach 1:
The patent extracts the cell retention function from complex mechanical systems and implements it using acoustic fields. Acoustic standing waves created by ultrasonic transducers generate acoustic radiation pressure that selectively retains cells at specific locations (nodes or antinodes) while allowing continuous flow of media and removal of byproducts, thereby eliminating the need for complex mechanical cell retention devices
Solution Approach 2:
The patent enables continuous operation by maintaining acoustic cell retention while continuously feeding fresh media and removing culture supernatant. This continuous operation eliminates the batch cycle downtime associated with fed-batch processes, allowing productivity to increase while the acoustic field system remains simpler than mechanical retention alternatives
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 acoustic perfusion devices achieve efficient cell separation and product harvesting, leading to lower overall cell culture media usage and significant cost savings, with cell densities up to 100 million cells/mL and reduced contamination, enhancing the attractiveness of perfusion bioreactor processes.
Implementation Method 1
at least one ultrasonic transducer in the acoustic chamber below the at least one harvest port, the at least one ultrasonic transducer including a piezoelectric material driven by a voltage signal to create an acoustic standing wave
Implementation Method 2
separating these desirable products from the cells on a continuous basis, and the cells are continuously returned to the bioreactor. Generally, a fluid mixture containing the cells and the desired products are passed or flowed through the acoustic device and separated therein by multi-dimensional standing wave(s)
Data Source
AI summary
Acoustic perfusion devices for separating biological cells from other material in a fluid mixture are disclosed. The devices include an inlet port, an outlet port, and a collection port that are connected to an acoustic chamber. An ultrasonic transducer creates an acoustic standing wave in the acoustic chamber that permits a continuous flow of fluid to be recovered through the collection port while keeping the biological cells within the acoustic chamber to be returned to the bioreactor from which the fluid mixture is being drawn.