Elliptical Filter for Rare Cell Isolation
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Solution Overview
Problem
Current methods for isolating and concentrating circulating tumor cells (CTCs) from blood face challenges such as low capture rates, cell damage, and difficulty in handling large blood volumes due to non-uniform filter densities and high deformability of CTCs, which complicates cancer diagnosis and analysis.
Innovation Solution
A filter with holes of 5 to 8 micrometers in minor axis diameter and 40 micrometers or more in major axis diameter, at a density of 40 to 2000 holes per square millimeter, with a ratio of major axis diameter to gap between holes between 7.0 and 130, is used to efficiently capture both small and highly deformable rare cells, reducing filtration pressure and cell damage.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If a filter with small hole diameter is used to capture rare cells, then the capture rate of small rare cells improves, but the filter clogs easily and requires high filtration pressure causing cell damage
Solution Approach 1:
The filter employs elliptical holes instead of circular holes, creating asymmetric geometry where the minor axis diameter (5-8 μm) is smaller than the major axis diameter (40 μm or more). This asymmetric shape allows rare cells to be captured by the smaller dimension while the larger dimension and appropriate hole density prevent clogging and reduce required filtration pressure.
2Reliability
If the number of filters is increased to treat larger blood volumes, then the detection probability of rare cells improves, but the operational complexity and handling difficulty increase
Solution Approach 1:
The filter surface is segmented into multiple regions with different hole densities (40-2000 holes/mm²). This segmentation allows different areas of the same filter to handle different cell types and blood volume requirements, enabling treatment of large blood volumes without increasing the number of filters.
Solution Approach 2:
Instead of increasing the number of filters (one-dimensional solution), the invention utilizes the two-dimensional filter surface area with variable hole density distribution. This allows processing of larger blood volumes by expanding the filtration area and optimizing hole density across the surface rather than stacking multiple filters.
3Ease of manufacture
If uniform filter density is used, then the manufacturing simplicity improves, but the capture efficiency for different cell types and large blood volumes deteriorates
Solution Approach 1:
The filter exhibits local quality variation through non-uniform hole density distribution across its surface. Different regions have different hole densities (40-2000 holes/mm²) optimized for capturing specific cell types or handling different blood flow rates, while maintaining manufacturability through controlled fabrication processes.
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 enhances the capture rate of rare cells, particularly CTCs, even with large blood volumes, while minimizing cell damage and operational complexity, allowing for more accurate cancer diagnosis and analysis.
Implementation Method 1
filtering a blood specimen using a filter to isolate or detect a rare cell in the blood specimen, the filter including holes having a minor axis diameter of 5 μm or more and 8 μm or less
Data Source
Figure 1A~1B
Figure 2
Figure 3~4
AI summary
A method for treating a blood specimen with which capture rates for both a small rare cell and a rare cell having high deformability can be improved in the case where rare cells are contained in a blood specimen. The method for isolating or detecting a rare cell includes treating a blood specimen using a filter to isolate or detect a rare cell in the blood specimen, the filter including holes having a minor axis diameter of 5 to 8 µm and a major axis diameter of 40 µm or more at a hole density of 40 to 2000 holes/mm2 with the ratio (w/z) between the major axis diameter w (µm) and a gap z (µm) between the holes in the minor axis diameter direction being 7.0 to 130.