Multilayered Inclined Settling Device for Cell Retention
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Solution Overview
Problem
Current cell retention devices in mammalian cell cultures, such as cyclones and inclined settlers, are inefficient in separating dead cells from live cells, leading to membrane clogging and premature termination of continuous perfusion bioreactors, especially when dealing with smaller microbial cells like yeast.
Innovation Solution
A settling device with multilayered, inclined surfaces arranged within a cyclone housing, featuring a stack of cones supported by projections to enhance particle settling efficiency, allowing bigger particles to settle on the surface and slide down vertically while smaller particles are removed through a top outlet, maintaining a high viability of live cells in the bioreactor.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional cyclones or inclined settlers are used for cell retention, then device simplicity is maintained, but cell separation efficiency deteriorates leading to membrane clogging and premature bioreactor termination
Solution Approach 1:
The settling device is divided into multiple functional zones: an upper cyclone section for initial separation and a lower inclined settler section for refined separation. This segmentation allows each zone to perform its specific function optimally, with the cyclone handling bulk separation and the inclined surfaces providing high-efficiency clarification, thereby preventing membrane clogging and extending bioreactor operation without sacrificing productivity
Solution Approach 2:
The patent combines two different separation mechanisms (cyclone separation and inclined settler separation) into a single integrated device. The cyclone portion provides centrifugal separation while the inclined surfaces provide gravitational settling, creating a hybrid system that achieves both high reliability and high productivity by leveraging the strengths of both methods
2Productivity
If centrifugal force is increased to improve cell separation, then separation efficiency improves, but mammalian cells are damaged
Solution Approach 1:
The device dynamically transitions from high centrifugal force in the upper cyclone section to low gravitational force in the lower inclined settler section. This dynamic force profile allows efficient separation of bulk material under high centrifugal force while final clarification occurs under gentle gravitational forces, preventing cell damage while maintaining high productivity
Solution Approach 2:
The inclined settler surfaces act as an intermediary between the high-force cyclone separation and the final low-force settling. This intermediary zone allows particles to gradually transition from centrifugal to gravitational separation, enabling efficient separation without subjecting delicate mammalian cells to damaging high centrifugal forces throughout the entire process
3Reliability
If inclined settlers are used to retain all mammalian cells, then cell retention is achieved, but dead cells accumulate and membrane filters clog
Solution Approach 1:
The device applies different separation qualities to different particle types: the cyclone section with higher centrifugal force selectively removes smaller dead cells and debris, while the inclined settler section with lower gravitational force retains larger live cells. This local differentiation of separation intensity prevents dead cell accumulation while maintaining cell retention, eliminating the harmful effect of filter clogging
4Device complexity
If fed-batch culture is used instead of continuous perfusion, then operational complexity is reduced, but protein productivity and culture duration are limited
Solution Approach 1:
The settling device enables the bioreactor system to self-regulate by automatically separating and removing dead cells and harvest product continuously. This self-service capability allows the system to maintain stable operation without complex external intervention, making continuous perfusion culture as manageable as fed-batch while achieving superior productivity and extended culture duration
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
This configuration significantly improves cell separation efficiency, enabling continuous high-density mammalian cell cultures by selectively removing dead cells and debris, thus extending the operation time of perfusion bioreactors and maintaining high cell viability and protein productivity.
Implementation Method 1
the particle separation devices of this disclosure may be used in numerous applications... gravitational settling in a cyclone... inclined settlers... The numerous, layered inclined plates enhance the settling efficiency of the particles from the bulk fluid
Implementation Method 2
A settling device with multilayered, inclined surfaces arranged within a cyclone housing... The inclined surfaces may be attached to a plurality of vertical cylindrical plates... The numerous, layered inclined plates enhance the settling efficiency
Data Source
Figure 1~3
Figure 4
Figure 5A~5C
AI summary
Settling devices for separating particles from a bulk fluid with applications in numerous fields. The particle settling devices include a first stack of cones with a small opening oriented upwardly or downwardly. Optionally, the settling devices may include a second stack of cones with a small opening oriented downwardly or upwardly. The cones may be concave or convex. These devices are useful for separating small (millimeter or micron sized) particles from a bulk fluid with applications in numerous fields, such as biological (microbial, mammalian, plant, insect or algal) cell cultures, solid catalyst particle separation from a liquid or gas and waste water treatment.