Cell selection chamber and methods of cell selection
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing methods for isolating target cells from a heterogeneous cell population, such as T-cells for CAR T-cell therapy, are inefficient and require strong magnets or large amounts of contaminants, leading to suboptimal processing efficiency and purity.
Innovation Solution
A cell selection chamber with streptavidin-coated microbubbles and controlled fluid flow circuits is used to selectively bind target cells to microbubbles, allowing for efficient separation and purification of target cells from other cellular components.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If magnetic particles are used to bind target cells, then cell separation can be achieved, but strong magnets are required which increases device complexity and processing difficulty
Solution Approach 1:
The patent replaces the mechanical magnetic field system with a fluid-based separation system. Streptavidin-coated microbubbles bind to target cells through biochemical affinity, and separation is achieved through controlled fluid flow and filtration rather than requiring strong magnets. This substitutes a complex mechanical magnetic system with a simpler fluid dynamics-based system.
Solution Approach 2:
The patent changes the binding mechanism from magnetic interaction to biochemical affinity interaction. By using streptavidin-coated microbubbles that bind to biotinylated antibodies on target cells, the system transforms the separation parameter from magnetic susceptibility to biochemical specificity, eliminating the need for strong magnetic fields.
2Reliability
If centrifugation or spinning membrane separation is used, then cell isolation can be achieved, but large amounts of contaminants are required which reduces processing efficiency
Solution Approach 1:
The patent extracts only the necessary target cells from the heterogeneous population using specific streptavidin-biotin binding, rather than requiring large volumes of cellular material for centrifugation or spinning membrane separation. This selective extraction approach improves processing efficiency by working with minimal necessary material.
Solution Approach 2:
The patent employs porous filtration membranes with controlled pore sizes to separate bound target cells from unbound cells and contaminants. The porous structure allows selective passage of different cell types based on size and binding status, achieving efficient isolation without requiring large amounts of contaminant material.
3Reliability
If conventional cell separation methods are used, then target cells can be isolated, but the purity is suboptimal requiring additional processing steps
Solution Approach 1:
The patent performs preliminary biotinylated antibody binding to target cells before the separation step. This preliminary action ensures that only target cells expressing the specific antigen will bind to streptavidin-coated microbubbles, enabling high-purity isolation in a single step without requiring additional purification processing.
Solution Approach 2:
The patent introduces streptavidin-coated microbubbles as an intermediary between the biotinylated antibodies on target cells and the separation process. This intermediary enables highly specific binding and efficient separation, achieving superior purity compared to conventional direct separation methods.
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 method achieves high purity and efficiency in isolating target cells by utilizing streptavidin-coated microbubbles, reducing the need for strong magnets and contaminants, and enabling automated, high-throughput cell processing.
Implementation Method 1
a heterogeneous population of cells is mixed with a biotinylated antibody additive... target cells to become bound to the microbubbles
Implementation Method 2
An upstream membrane is positioned between the inlet and the reservoir, while a downstream membrane is positioned between the outlet and the reservoir, with the membranes including a plurality of pores each having a diameter less than a diameter of the microbubbles
Data Source
Figure 1~2
Figure 3A~3C
Figure 4~5
AI summary
A cell selection chamber includes an inlet and an outlet, with a reservoir positioned therebetween and configured to allow for fluid flow from the inlet to the outlet. The reservoir contains a plurality of microbubbles, which are each at least partially coated with streptavidin. An upstream membrane is positioned between the inlet and the reservoir, while a downstream membrane is positioned between the outlet and the reservoir. The membranes include a plurality of pores each having a diameter that is less than a diameter of the microbubbles. In use, a heterogeneous population of cells is mixed with a biotinylated antibody additive and then conveyed into the cell selection chamber so as to cause target cells of the heterogeneous population of cells to become bound to the microbubbles and to cause other cells of the heterogeneous population of cells to flow out of the cell selection chamber as unbound cells.