Well Array Filter With Multi-Hole Well Bottoms for Single-Cell Capture
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Solution Overview
Problem
Existing well array filters face challenges in achieving high single cell capture rates while maintaining liquid permeability, as increasing well opening diameter reduces the number of wells per unit area and decreasing it leads to reduced liquid permeability and increased risk of cells passing through the through-holes.
Innovation Solution
The well array filter design includes a flat filter body with open wells separated by partition walls, featuring two or more through-holes in the well bottom portion, with specific dimensions and positional relationships to ensure high single cell capture rates and stable liquid permeability, using materials like MPC polymer to restrict cell adhesion and enhance handling.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If the opening diameter of the well is increased to facilitate cell culture and capillary handling, then the ease of operation is improved, but the number of wells per unit area decreases, reducing productivity
Solution Approach 1:
The well bottom portion is segmented into multiple through-holes (two or more) instead of a single through-hole. This segmentation allows the filter to maintain smaller well openings for higher density while providing multiple escape paths for cells, resolving the contradiction between well size and capture efficiency
Solution Approach 2:
The through-holes are positioned specifically at the bottom portion of the wells with controlled dimensions (minimum width 1-3.5 μm). This local optimization of the bottom structure allows selective cell passage while maintaining the overall well integrity and appropriate size for handling, addressing the contradiction between well size and cell capture
2Productivity
If the opening diameter of the well is decreased to increase the number of wells per unit area, then the productivity is improved, but the liquid permeability deteriorates and the risk of cells passing through through-holes increases
Solution Approach 1:
The well bottom portion is designed as a porous structure with multiple through-holes instead of a single opening. This porous configuration maintains adequate liquid permeability even when well openings are small, as the cumulative area of multiple small through-holes provides sufficient flow paths while preventing cell passage through the controlled hole dimensions
Solution Approach 2:
The single through-hole is segmented into multiple smaller through-holes (two or more) at the well bottom. This segmentation increases the total surface area for liquid permeation while maintaining individual hole dimensions that prevent cell passage, thus improving reliability of liquid flow in high-density well arrays
3Reliability
If the number of through-holes is increased to improve liquid permeability, then the liquid permeability is improved, but the single cell rate decreases as cells may pass through multiple holes
Solution Approach 1:
The dimensions of through-holes are precisely controlled within specific ranges (minimum width 1-3.5 μm) to match cell sizes. This parameter optimization ensures that while multiple through-holes provide sufficient liquid permeability, the controlled dimensions prevent cell passage through the holes, maintaining high single cell capture rates
Solution Approach 2:
The through-holes are positioned specifically at the bottom portion of wells with controlled dimensions and spacing. This localized optimization ensures that the through-holes are small enough to prevent cell passage while providing adequate liquid flow paths, resolving the contradiction between permeability and single cell capture
Data Source
Figure 1~2
Figure 3(a)~3(c)
Figure 4(a)~4(c)
AI summary
In a well array filter (1), a plurality of wells (3) are formed in a filter body (2), the wells (3) adjacent to each other are separated by a well partition wall (6), two or more through-holes (8) are formed in a well bottom portion (4), the minimum width of the opening of the through-hole (8) is 1 µm or more and 3.5 µm or less, and the ratio of a total opening area of the through-hole is 0.5% or more and 3.5% or less. Assuming a minimum circumscribed circle (G1) that surrounds all of the through-holes (8) in each well bottom portion (4), when the center is moved to the center of each of the plurality of through-holes (8), all minimum circumscribed circles (G2) after movement at least partially overlap all of the plurality of through-holes (8).