Microscale Cell Filter for CTC Isolation
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Solution Overview
Problem
Current methods for isolating circulating tumor cells (CTCs) from blood samples are inefficient due to their low concentration and reliance on costly, time-consuming processes that require staining or antibodies, which can lead to misleading results due to phenotypical variations of CTCs during Epithelial Mesenchymal Transition.
Innovation Solution
A microscale cell filter with an inlet and outlet flow channel and post elements forming gaps of 3 to 6 micrometers, allowing cells to be trapped based on size and deformability, independent of staining or antibodies, enabling real-time snapshot of tumor burden and easy manufacturing.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If immunofluorescence analysis with antibodies targeting cytokeratins is used to isolate CTCs, then CTCs can be identified based on EPCAM expression, but the method fails to detect CTCs that have undergone Epithelial Mesenchymal Transition (EMT) and presents misleading results
Solution Approach 1:
The invention changes the detection parameter from molecular markers (EPCAM, cytokeratins) to physical parameters (size, deformability). By using gaps of 3-6 micrometers and aspect ratios of 3.5-5, the filter captures CTCs based on their physical characteristics rather than phenotypical markers, enabling detection of all CTC sub-populations including those that have undergone EMT.
2Measurement precision
If staining or antibody-based methods are used for CTC isolation, then specific CTC populations can be identified, but the process becomes costly and time-consuming
Solution Approach 1:
The invention replaces complex biochemical methods (staining, antibody incubation, fluorescence detection) with a simple mechanical filtration system. The microscale cell filter uses physical structures (posts with specific gaps and aspect ratios) to separate CTCs from blood cells based on size and deformability differences, eliminating the need for time-consuming staining and antibody-based procedures.
3Productivity
If a filter with smaller gaps is used to trap CTCs, then CTC isolation efficiency improves, but flow pressure significantly increases and may clog the filter
Solution Approach 1:
The invention transitions from considering only gap width to incorporating gap aspect ratio as a critical dimension. By creating gaps with width of 3-6 micrometers and height of 10-30 micrometers (aspect ratio 3.5-5), the filter provides sufficient trapping efficiency for CTCs while maintaining adequate flow pressure, as the elongated gap geometry allows blood cells to pass through more easily.
4Productivity
If complex multi-layered filter structures are used to improve filtration performance, then cell separation efficiency increases, but manufacturing complexity and cost increase
Solution Approach 1:
The invention segments the filtration function into two independent geometric parameters: gap width (3-6 micrometers) for CTC trapping and gap aspect ratio (3.5-5) for maintaining flow. This segmentation allows each parameter to be optimized independently and simplifies manufacturing, as the filter can be fabricated as a single-layer structure with posts of specific dimensions rather than complex multi-layered assemblies.
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
Enables efficient isolation of CTCs by size and deformability, reducing the need for costly and time-consuming processes, allowing for accurate prognosis and personalized treatment monitoring without pre-treatment of samples, and facilitating easy integration with biosensors for phenotypic and molecular profiling.
Implementation Method 1
the plurality of post elements is arranged such that a width of each gaps is 3 to 6 micrometers; and wherein each of the plurality of post elements has an elongation such that each gap has an aspect ratio between its width and its height being larger than 3.5, preferably in the range of 3.5 to 5, thereby trapping the sub-portion of the cells within the sample
Implementation Method 2
In the case of cells being larger than a gap, but deformable, the cells may squeeze through the gap from the inlet flow channel to the outlet flow channel using the elongation of the gap. This is the case for most cells in blood. For example, red blood cells have an average diameter of 6-8 micrometers, but may be deformed by the pressure from the flow against the post elements which enables the cells to pass through.
Data Source
AI summary
A microscale cell filter for trapping a sub-portion of cells within a sample is provided. The cell filter comprises: an inlet flow channel; an outlet flow channel; and a plurality of post elements arranged between the inlet flow channel and the outlet flow channel, wherein the plurality of post elements is interspaced, thereby forming a plurality of gaps, each gap being formed in between two adjacent post elements; wherein the plurality of post elements is arranged such that a flow of the sample flowing from the inlet flow channel to the outlet flow channel passes through the plurality of gaps; wherein the plurality of post elements is arranged such that a width of each gaps is 3 to 6 micrometers; and wherein each of the plurality of post elements has an elongation such that each gap has an aspect ratio between its width and its height being larger than 3.5, thereby trapping the sub-portion of the cells within the sample at an upstream side of the plurality of post elements.