Cell Rolling Separation via Adhesion Edge Design
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Solution Overview
Problem
Current methods for cell separation based on cell rolling are limited in their ability to efficiently divert cells from their direction of flow using existing receptor-ligand interactions, particularly in applications requiring precise control over cell trajectory and separation.
Innovation Solution
The use of surfaces with ordered layers of cell adhesion molecules, featuring edges or stagnation lines, to alter the direction of cell motion by interacting with cells flowing across them, allowing for selective separation of cell populations based on their interaction with these surfaces.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If cell rolling is used for cell separation, then cells can be separated based on their interaction with adhesion molecules, but the ability to efficiently divert cells from their direction of flow is limited
Solution Approach 1:
The patent applies local quality by creating localized regions with different adhesion molecule densities on the surface. Areas with high adhesion molecule density cause cells to roll and divert, while areas with low density allow cells to pass through. This spatial variation in adhesion molecule distribution enables efficient cell diversion and separation without requiring complete coverage of the entire surface.
Solution Approach 2:
The patent utilizes asymmetry by designing surfaces where adhesion molecules are distributed non-uniformly, creating preferential paths for cell rolling. The asymmetric arrangement of adhesion molecules causes cells to follow specific trajectories rather than moving randomly, thereby improving the efficiency of cell diversion from the bulk flow direction.
2Manufacturing precision
If surfaces are coated with cell adhesion molecules to alter cell direction, then cell trajectory control is improved, but the complexity of the surface structure increases
Solution Approach 1:
Instead of uniformly coating the entire surface with adhesion molecules, the patent applies adhesion molecules only to specific localized regions. This approach maintains manufacturing simplicity while achieving precise cell trajectory control, as cells interact with adhesion molecules only in the designated areas rather than across the entire surface.
Solution Approach 2:
The patent segments the surface into distinct regions with different adhesion molecule densities or presences. This segmentation allows for simplified manufacturing of each region while collectively achieving complex cell sorting functionality, reducing the overall device complexity compared to a uniformly coated surface.
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 approach enables precise control over cell trajectory and efficient separation of cell populations by altering their direction of motion, enhancing the ability to isolate specific cells while maintaining their physiological integrity.
Implementation Method 1
Cell rolling is a receptor-ligand mediated event that initiates an adhesion process to a target tissue through a reduction in cell velocity. The rolling response is primarily mediated by a family of transmembrane glycoprotein receptors called selectins, which are expressed on the surfaces of leukocytes and activated endothelial cells. Selectins bind to carbohydrates via a lectin-like extracellular domain.
Implementation Method 2
Once captured, cells roll slowly over the surface, in contrast to uncaptured cells, which flow rapidly in the bulk fluid.
Data Source
AI summary
The present invention provides systems for cell separation based on cell rolling on surfaces along edges of regions coated with cell adhesion molecules. A variety of designs of coated regions and edges are disclosed.