Cell Separation Device Using Segmented Shear Flow
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Solution Overview
Problem
Current methods for separating cells from microcarriers are inefficient and often damage cells, lacking effective devices and systems for gentle detachment and harvesting of single cells.
Innovation Solution
A cell separation system comprising a conduit, a cell shear device with multiple fluid flow paths, a cell settling device with flexible bags and multiple ports, and a cell screening device with a porous element to separate cells from microcarriers, allowing for gentle detachment and retention of microcarriers.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If current separation methods are used to detach cells from microcarriers, then cells can be separated, but cell damage occurs and efficiency is low
Solution Approach 1:
The device segments the fluid flow into multiple parallel paths (first and second fluid flow paths, each with multiple sub-flow paths) to distribute the shear stress across numerous smaller channels. This segmentation allows effective cell detachment through controlled shear forces while preventing excessive stress concentration that would damage cells.
Solution Approach 2:
The connectors in the sub-flow paths have varying internal diameters (at least one connector has an internal diameter less than the inlet and outlet diameters), creating localized regions of different flow characteristics. This local variation in geometry optimizes shear stress distribution at specific points where cell detachment is needed while protecting cells in other regions.
2Productivity
If enzymes are used to detach cells from microcarriers, then cell detachment can be achieved, but enzyme concentration must be high and process complexity increases
Solution Approach 1:
The invention replaces chemical detachment methods (enzymes) with a mechanical system consisting of multiple flow paths and connectors that generate controlled shear forces. This mechanical approach achieves cell detachment through physical means alone, eliminating or reducing the need for enzymes and simplifying the overall process.
3Productivity
If single-cell suspension is produced, then cell harvesting is improved, but separation precision must be high to avoid microcarrier contamination
Solution Approach 1:
The device uses multiple parallel flow paths with numerous connectors to create extensive fluid distribution. This segmented approach ensures thorough mixing and separation throughout the device, achieving high precision in separating cells from microcarriers and producing clean single-cell suspensions.
Solution Approach 2:
The varying connector diameters create localized flow conditions that optimize separation at different points in the device. This local quality variation ensures that cells are effectively separated from microcarriers while maintaining high precision throughout the entire separation process.
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 effectively detaches cells from microcarriers while minimizing cell damage, producing a suspension of single cells for further use without enzymes or with reduced enzyme concentration, suitable for various cell types and microcarriers.
Implementation Method 1
a cell shear device, interposed between, and in fluid communication with, the inlet and the outlet, the shear device comprising a plurality of fluidly connected conduits arranged to provide at least a first fluid flow path and a second fluid flow path
Implementation Method 2
a cell settling device comprising (a) a flexible bag having an interior volume... (b) a plurality of ports in fluid communication with the interior volume of the flexible bag
Implementation Method 3
a cell screening device comprising at least one inlet port and at least one outlet port, an interior volume, and a porous element between the at least one inlet port and the at least one outlet port, the ports allowing fluid to pass into and/or out of the cell screening device
Data Source
AI summary
Cell separation systems, and methods for separating cells from microcarriers, and harvesting the separated cells, are provided, wherein the system comprises a cell separation device, a cell settling device, and a cell screening device.