Integrated DLD Chip for CTC Separation and Capture
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Solution Overview
Problem
Current methods for separating and capturing Circulating Tumor Cells (CTCs) face challenges such as low purity, cell damage due to multi-step operations, and inefficient separation throughput, particularly with traditional Deterministic Lateral Displacement (DLD) chips that require high flow velocities and result in incomplete separation of CTCs from leukocytes and erythrocytes.
Innovation Solution
An integrated chip with a cell separation region and capture region, utilizing multiple sets of symmetrical DLD micropost arrays with a gradually increased critical sorting diameter and inclination angle, allowing for one-step separation and capture of CTCs based on size, improving purity and reducing cell damage through in-situ capture and reduced operational steps.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If traditional DLD chips are used for cell separation, then separation throughput can be improved, but cell damage occurs due to high flow velocities required
Solution Approach 1:
The chip structure transitions from a static traditional DLD design to a dynamic microfluidic system where flow velocity and pressure are optimized to achieve separation without damaging cells. The gradual increase in micropost array inclination angles creates a dynamic separation process that adapts to different cell sizes while maintaining gentle flow conditions.
Solution Approach 2:
The invention changes key parameters including the gradual increase in micropost array inclination angles from 15° to 75°, and optimizes flow velocity to range from 0.5-5 mm/s. These parameter changes enable effective separation while avoiding the high flow velocities that cause cell damage in traditional DLD systems.
2Manufacturing precision
If multi-step operations are used for cell separation and capture, then separation purity can be improved, but cell damage increases due to repeated handling
Solution Approach 1:
The invention merges cell separation and cell capture functions into a single integrated chip structure. The separation region with gradient micropost arrays directly connects to the capture region with magnetic beads, eliminating the need for intermediate transfer steps and reducing cell damage from repeated handling while maintaining high separation purity.
Solution Approach 2:
The integrated chip performs multiple functions (separation, capture, and enrichment) within a single device structure. The micropost arrays serve both as separation elements and as support structures for magnetic bead attachment, enabling multi-functionality without requiring multiple separate devices or操作步骤.
3Device complexity
If traditional DLD chips with fixed micropost arrays are used, then device complexity can be reduced, but separation precision decreases due to incomplete separation of CTCs from leukocytes and erythrocytes
Solution Approach 1:
The micropost arrays are segmented into multiple regions with gradually increasing inclination angles (15°, 30°, 45°, 60°, 75°). This segmentation allows different size ranges of cells to be separated at different stages, improving separation precision while maintaining a relatively simple overall chip structure that can be manufactured using standard microfabrication techniques.
4Productivity
If one-step separation and capture is implemented, then operational efficiency is improved, but separation purity may decrease compared to multi-step methods
Solution Approach 1:
Different regions of the chip are designed with locally optimized properties: the separation region has gradient micropost arrays with specific inclination angles for size-based separation, while the capture region has magnetic beads for targeted CTC capture. This local quality optimization ensures high separation purity is achieved within the single-step integrated process.
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
The integrated chip achieves high-efficiency, high-purity separation and capture of CTCs, enhancing separation throughput and cell viability by integrating enrichment, separation, and capture processes into a single step, reducing manual intervention and detection costs.
Implementation Method 1
separation methods based on the physical characteristics of the cells are developed by researchers. The physical characteristics of the tumor cells, such as size and density, are greatly different from those of the leukocytes and the erythrocytes. Common separation methods based cell sizes are, for example, filter membranes, inertia force, vortex, Deterministic Lateral Displacement (DLD), etc.
Implementation Method 2
The cell capture region includes magnetic beads for capturing the target cells
Data Source
AI summary
The present disclosure relates to an integrated chip, which includes a cell enrichment region, a cell separation region and a cell capture region, wherein one end of the cell enrichment region is provided with an inlet, and the other end of the cell enrichment region is provided with a waste liquid outlet and an enriched liquid outlet; one end of the cell separation region is provided with a buffer solution inlet and an enriched liquid inlet , and the other end of the cell separation region is provided with an outlet; one end of the cell capture region is provided with an inlet, and the other end of the cell capture region is provided with a separated liquid outlet. Compared with the traditional technology, the chip can separate a target cell from a to-be-treated cell solution with a high efficiency, and capture the target cell in situ in a chip.