Acoustic Perfusion Devices for Bioreactor 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, limiting their attractiveness despite offering higher cell densities and lower contamination in pharmaceutical production.
Innovation Solution
Acoustic perfusion devices generate multi-dimensional acoustic standing waves to separate biomolecules from cells, allowing continuous recycling of healthy cells back to the bioreactor while harvesting desired products, reducing nonproductive downtime and operational complexity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If traditional cell retention systems are used in perfusion bioreactors, then cell separation and product harvesting are achieved, but device complexity and operational maintenance requirements increase
Solution Approach 1:
The patent replaces mechanical cell retention systems (filters, membranes, centrifuges) with an acoustic field-based separation system. Ultrasonic transducers generate acoustic standing waves that create radiation forces to separate cells from the culture medium based on acoustic impedance differences, eliminating moving mechanical parts while achieving effective cell retention and product harvesting
2Productivity
If perfusion bioreactors operate continuously with cell retention systems, then higher cell densities and lower contamination are achieved, but operational reliability decreases due to potential malfunction
Solution Approach 1:
The acoustic-based cell retention system replaces mechanical systems that are prone to clogging, fouling, and mechanical failure. The ultrasonic field dynamically separates cells without physical contact, eliminating wear and tear on mechanical components while maintaining high cell density and continuous operation reliability
Solution Approach 2:
The system dynamically adjusts acoustic parameters (frequency, power, wave patterns) to optimize cell separation under different operating conditions. This adaptability allows the system to maintain reliable performance across varying cell densities, media compositions, and flow rates without mechanical adjustments or maintenance
3Ease of operation
If fed-batch bioreactors are used, then operational simplicity is maintained, but nonproductive downtime increases due to cleaning and sterilization
Solution Approach 1:
The acoustic perfusion system enables continuous operation by maintaining effective cell separation throughout the culture process. The acoustic field remains active and effective throughout, allowing continuous harvesting without batch interruptions for cleaning or sterilization, thus eliminating nonproductive downtime while maintaining operational simplicity
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, reducing contamination and increasing yields, with potential cost savings of up to $20,000 per day for large bioreactors, while maintaining cell viability and reducing operational complexity.
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 across a collection or harvest flow path leading from the acoustic chamber to the at least one collection or harvest port
Implementation Method 2
the acoustic standing wave results in an acoustic radiation force having an axial force component and a lateral force component that are of the same order of magnitude
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.