Microscale Cell Filter for CTC Isolation
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Solution Overview
Problem
Current methods for isolating circulating tumor cells (CTCs) are inefficient, costly, time-consuming, and often rely on staining or antibodies, which can lead to misleading results due to the heterogeneity of CTC sub-populations and their low concentration in blood samples.
Innovation Solution
A microscale cell filter with a design featuring an inlet and outlet flow channel and post elements arranged perpendicular to the flow direction, creating gaps of specific widths and aspect ratios to trap cells based on size and deformability, allowing for physical separation and isolation without the need for staining or antibodies.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If EpCAM expression or immunofluorescence analysis with antibodies targeting cytokeratins is used for CTC isolation, then CTCs can be identified based on specific markers, but the method fails to account for CTC heterogeneity and Epithelial Mesenchymal Transition (EMT) sub-populations, leading to misleading results
Solution Approach 1:
The invention changes the isolation parameter from molecular markers (EpCAM, cytokeratins) to physical parameters (size, deformability). The microfluidic device uses gaps with specific width (3-8 micrometers) and aspect ratios (3.5-5) to physically separate CTCs from blood cells based on their size and deformability characteristics, which remain consistent across different CTC phenotypes including EMT sub-populations.
Solution Approach 2:
The invention replaces the biochemical/mechanistic approach (antibody-based immunofluorescence) with a purely mechanical physical filtration system. The microfluidic chip uses engineered gap geometries to mechanically filter and trap CTCs based on their physical properties, eliminating the need for staining or molecular marker detection.
2Measurement precision
If conventional CTC isolation methods are used, then CTCs can be detected, but the process is costly, time-consuming, and complex requiring multiple steps and specialized reagents
Solution Approach 1:
The invention extracts the essential isolation function from complex biochemical procedures and implements it through a simple physical filtration mechanism. The microfluidic device contains only the necessary structural elements (channels, gaps, post elements) to perform separation, removing the need for antibodies, stains, and complex processing steps.
Solution Approach 2:
The invention uses a porous-like structure with defined gaps between post elements to achieve filtration. The gaps have specific dimensions (width 3-8 micrometers, aspect ratio 3.5-5) that allow smaller blood cells to pass through while trapping larger CTCs, functioning as a size-based physical filter without requiring complex materials or multi-layer structures.
3Measurement precision
If CTCs are isolated using marker-based methods, then epithelial CTCs can be detected, but CTCs undergoing Epithelial Mesenchymal Transition (EMT) with different phenotypes are missed or misidentified
Solution Approach 1:
The invention creates a universal isolation mechanism that works for all CTC types regardless of their phenotypic state. The physical filtration based on size and deformability applies equally to epithelial CTCs, mesenchymal CTCs, and hybrid states, making the device universally effective across the entire spectrum of CTC heterogeneity without needing to adapt to specific marker expressions.
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, cost-effective, and real-time isolation of CTCs by filtering cells based on size and deformability, providing accurate tumor burden snapshots and enabling further analysis, including in-situ analysis or culturing of trapped cells, with high purity and efficiency.
Implementation Method 1
The microscale cell filter physically separates and isolates cells, enabling their enumeration and characterization. The low invasive technique according to the present invention filters cells by size and deformability.
Implementation Method 2
Cells, e.g. CTCs, that are larger than the gaps and are substantially rigid may be trapped in the filter. For example, if a rigid cell has a diameter of 8 micrometers and the gap is between 3 to 8 micrometers, the cell may be trapped in the filter.
Data Source
AI summary
A microscale cell filter for separating and isolating cancer cells within a sample having an inlet flow channel; an outlet flow channel; and a single row of a plurality of post elements between the inlet flow channel and the outlet flow channel, the plurality of post elements being interspaced, forming a plurality of gaps, each gap formed in between two adjacent post elements; the plurality of post elements is arranged such that a sample flowing from the inlet flow channel to the outlet flow channel passes through the plurality of gaps; the plurality of post elements is arranged such that a width of each gaps is 3 to 8 micrometers; and each gap has an aspect ratio between its height and width in the range of 3.5 to 5, thereby trapping the cells within the sample at an upstream side of the single row of a plurality of post elements.