Disposable ATF Housing with Threaded Pump Chamber
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Solution Overview
Problem
The development of a disposable, alternating tangential flow filtration (ATF) device that can withstand significant pressures and maintain sterility is challenging due to the need for materials that are both robust and non-toxic, as traditional metallic components are not suitable for disposable systems and adhesives used to enhance strength are toxic to cells.
Innovation Solution
A disposable ATF device featuring a sterilizable plastic housing with a clamp ring and internally threaded hemispherical pump chamber halves, along with a specially designed diaphragm, allows for robust construction and sealing while maintaining sterility, using materials like acrylonitrile-butadiene-styrene and polysulfone plastics, and incorporating a mechanism for flushing and wetting the filter without introducing contaminants into the bioreactor.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional metallic components are used for ATF devices, then the device can withstand significant pressures and maintain structural integrity, but the device cannot be disposable and requires complex sterilization processes
Solution Approach 1:
The patent applies this principle by designing a complete disposable ATF device made from sterilizable plastic components including a housing, diaphragm pump, and filter assembly. The device is intended for single-use to eliminate sterilization requirements while maintaining pressure withstanding capability through proper material selection and structural design, directly resolving the contradiction between disposability and pressure resistance
2Strength
If adhesives are used to enhance the strength of plastic components, then the structural integrity improves, but the adhesives are toxic to cells in bioreactor applications
Solution Approach 1:
The patent applies this principle by completely eliminating adhesives from the device construction. Instead of using adhesives to join components, the design employs mechanical attachment methods such as threaded connections, snap-fits, and integrated molding that provide sufficient structural integrity without introducing toxic substances into the bioreactor environment
3Reliability
If the filter is sterilized using gamma radiation or ethylene oxide, then sterility is achieved, but the dry filter must be flushed and wetted before use to obtain efficient perfusion
Solution Approach 1:
The patent applies this principle by incorporating a pre-wetting mechanism into the device design that automatically wets the filter membrane during the initial flushing operation. The housing includes integrated fluid pathways and reservoirs that deliver wetting solution to the filter before use, eliminating the need for separate manual wetting steps while maintaining sterility through radiation or chemical sterilization
4Adaptability or versatility
If a disposable design is implemented, then cost and flexibility improve, but the device must withstand significant pressures without the reinforcement provided by metallic components
Solution Approach 1:
The patent applies this principle by using composite plastic constructions including reinforced thermoplastics, multi-layer molded structures, and integrated support ribs within the housing and pump components. These composite designs provide the necessary pressure resistance typically associated with metallic components while maintaining the disposable nature and flexibility of plastic construction
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 solution enables the creation of a robust, sterile, and cost-effective disposable ATF device capable of withstanding pressures up to 50 psi, ensuring efficient perfusion and integrity testing, reducing contamination risks, and simplifying handling and disposal, while maintaining optimal filtration performance in high-density cell culture processes.
Implementation Method 1
The diaphragm pump provides the means for generating rapid, alternating, low shear tangential flow between the vessel and pump and through the hollow fibers or screen filter
Implementation Method 2
a hollow fiber filter membrane of appropriate pore size to retain the cells
Data Source
Figure 1A
Figure 1B~1C
Figure 2A
AI summary
Disclosed herein are robust disposable alternating tangential flow (ATF) housing and diaphragm pump units and associated methods of manufacturing, testing, wetting, and using the same.