Microchannel Chip CTC Separation Meniscus Capture
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current methods for detecting circulating tumor cells (CTCs) in blood are inefficient, often requiring pretreatment and the use of anti-EpCAM antibodies, which can miss CTCs that are EpCAM-negative or slightly positive, and involve complex equipment and procedures that are not suitable for bedside diagnostics.
Innovation Solution
A microchannel chip with main channels and capture portions of greater width, and branching channels that allow CTCs to be separated and captured using a meniscus generated by relative movement of sample and sheath liquids, without the need for anti-EpCAM antibodies, enabling continuous separation and recovery of CTCs from whole blood.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If anti-EpCAM antibody-based methods are used for CTC concentration, then CTCs can be targeted and concentrated, but EpCAM-negative or slightly positive tumor cells cannot be detected and the expression level of EpCAM varies considerably depending on tumor type
Solution Approach 1:
The invention extracts the CTCs from blood based on their physical size property rather than chemical antigen properties. By using size-based filtration through microchannels with specific pore sizes (8-15 μm for epithelial tumor cells), the method removes the dependency on EpCAM antibody expression and captures all CTCs regardless of their antigen profile.
Solution Approach 2:
The invention changes the separation parameter from chemical (EpCAM antigen-antibody interaction) to physical (cell size). By adjusting the pore size of the filter or microchannel dimensions to match the size range of CTCs, the system achieves universal detection across different tumor types without being constrained by variable antigen expression levels.
2Ease of manufacture
If ISET method with polycarbonate membrane filter is used, then the method is simple and inexpensive, but the pores have relatively low density and two or more pores overlap resulting in only 50-60% capture efficiency
Solution Approach 1:
The invention uses microfluidic pressure-driven flow through precisely engineered microchannels to achieve controlled cell separation. By applying hydrodynamic pressure to push cells through size-selective microchannel filters, the system achieves high capture efficiency while maintaining operational simplicity and low cost.
Solution Approach 2:
The invention changes the filter structure from random pore patterns in polycarbonate membranes to precisely controlled microchannel geometries fabricated by photolithography. This allows exact control over pore size, pore density, and channel dimensions to match the size distribution of target CTCs, achieving >90% capture efficiency.
3Reliability
If Cellsearch device is used for CTC detection, then CTCs can be concentrated and detected, but large-scale equipment is required and it is difficult to perform accurate bedside examinations in a short period of time
Solution Approach 1:
The invention segments the CTC detection process into simple, discrete steps: blood sample introduction, size-based filtration through microchannel arrays, and direct analysis of captured cells. This segmentation eliminates the need for complex magnetic particle immunoenrichment and automated fluorescence microscopy systems, enabling simplified bedside operation.
Solution Approach 2:
The invention replaces the complex mechanical and optical systems of Cellsearch (magnetic separation, automated imaging, fluorescence detection) with a simple size-based physical filtration system. The microchannel filter array performs enrichment purely on geometric grounds, eliminating the need for expensive magnets, antibody coatings, and automated microscopy equipment.
4Productivity
If CTC-chip with micro-posts is used, then the device is small and can provide direct analysis of 5 mL or more of blood, but EpCAM-negative or slightly positive tumor cells cannot be detected because it operates on anti-EpCAM antibody principle
Solution Approach 1:
The invention extracts the size-based separation principle from the antibody-dependent CTC-chip design. By removing the anti-EpCAM antibody coating from the micro-post surfaces and relying solely on geometric size exclusion through microchannel filters, the system achieves both high throughput (5 mL+ blood processing) and universal detection of all CTC phenotypes.
Solution Approach 2:
The invention changes the capture mechanism parameter from chemical (antibody-antigen binding) to physical (size-based geometric exclusion). By designing microchannel dimensions that correspond to the size range of CTCs rather than relying on molecular recognition, the system maintains the miniaturized format and high throughput capability while achieving phenotype-independent detection.
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 method allows for precise, rapid separation of CTCs from whole blood without pretreatment, reducing equipment complexity and cost, and enabling reliable detection of CTCs, including those that are EpCAM-negative, facilitating bedside cancer diagnosis.
Implementation Method 1
a microchannel chip for microparticle separation, a thin plate for a sample liquid, and a thin plate for a sheath liquid are caused to move in a relative fashion to thereby generate a meniscus
Implementation Method 2
a force generated by a meniscus at the air-liquid boundary so that it is possible to capture only objective microparticles in capture portions provided in the microchannels
Data Source
Figure 1~2(2)
Figure 3
Figure 4(1)~5
AI summary
Provided is a microchannel chip, for microparticle separation, which can continuously separate microparticles, from a solution in which microparticles of different particle diameter are mixed, without needing to use an antibody or similar, and without causing clogging. Also provided are a microparticle separation method and a system for microparticle separation using the chip. Microparticles can be captured by using the microchannel chip for microparticle separation, the microchannel chip being characterised by being provided with a plurality of main channels and capture portions that are wider than the main channels and at least one of which is provided to each main channel.