Micro-channel Chip Hydraulic Classification for Rare Cell Concentration
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Solution Overview
Problem
Current methods for concentrating rare target cells, such as fetal-derived nucleated red blood cells, from whole blood are inefficient, particularly in noninvasive prenatal genetic testing, due to limitations in processing large volumes and high cell densities, leading to insufficient concentration of these rare cells.
Innovation Solution
A micro-channel chip with a specific pattern of main, sub, removal, and collection channels, where fluid flow directs non-nucleated red blood cells into removal channels and target cells into collection channels, allowing for efficient separation and concentration of rare cells through hydraulic classification, with multiple layers and controlled fluid flow rates.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional concentration methods are used, then the process is simple, but the concentration efficiency of rare target cells is insufficient
Solution Approach 1:
The chip is divided into multiple functional regions including a classification channel, removal channel, and collection channel. The classification channel is further segmented into a first classification region and a second classification region with different channel widths, allowing staged separation of blood cells based on size. This segmentation enables efficient concentration of rare target cells while maintaining a manageable chip structure.
Solution Approach 2:
The patent transitions from conventional single-channel or simple multi-channel designs to a two-dimensional network of interconnected channels. The classification channel branches into removal and collection channels, creating a planar separation architecture that efficiently directs different cell types to different outlets based on their hydraulic diameter, thereby improving concentration efficiency without excessive vertical complexity.
2Quantity of substance
If the chip processes large volumes of whole blood, then more target cells can be obtained, but the processing time increases
Solution Approach 1:
The chip design incorporates a preliminary classification stage in the first classification region where large non-nucleated red blood cells are rapidly separated from the blood sample. This preliminary action removes the majority of bulk cells before the sample enters the second classification region, thereby reducing the time required to process large volumes while still capturing rare target cells in the collection channel.
Solution Approach 2:
The patent uses a two-stage classification approach where the first classification region performs a coarse separation to remove the majority of non-target cells, and the second classification region performs a finer separation to isolate rare target cells. This partial action strategy processes large volumes efficiently by not requiring every cell to undergo the full separation process, thus reducing overall processing time while maintaining high target cell recovery.
3Measurement precision
If a single classification channel is used, then the device is simple, but the separation precision of different cell types is insufficient
Solution Approach 1:
The classification channel is segmented into two distinct regions with different channel widths. The first classification region has a wider channel suitable for removing large non-nucleated red blood cells, while the second classification region has a narrower channel optimized for isolating smaller target cells. This segmentation of the single classification channel into functional zones improves separation precision without requiring multiple independent channels, thus balancing complexity and performance.
4Adaptability or versatility
If prior density gradient centrifugation is performed, then the sample is pre-separated, but the chip cannot process whole blood directly
Solution Approach 1:
The chip incorporates a removal channel branching from the classification channel, creating a three-way separation network. This segmentation allows the chip to handle whole blood directly by routing different cell types to different channels: non-nucleated red blood cells to the removal channel, and target cells to the collection channel. The segmented channel architecture provides the versatility to process various sample types without requiring pre-separation steps.
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 enables the efficient concentration of rare target cells from whole blood samples, improving the yield and purity of fetal-derived nucleated red blood cells for prenatal genetic testing, even with limited sample volumes and time constraints.
Implementation Method 1
a micro-channel unit for hydraulically classifying cells in a blood sample
Data Source
AI summary
A chip includes a micro-channel unit for hydraulically classifying cells in a blood sample. In a micro-channel unit, liquid flowing from a sub channel into a main channel pushes cells flowing in the main channel toward a side thereof on which a removal channel and a collection channel are disposed. Fluid containing non-nucleated RBCs among the pushed cells enters the removal channel, so that the non-nucleated RBCs are removed from a blood sample. A plurality of micro-channel units having the same patterns as each other are repeatedly stacked in a height direction. Inlets of the main channels, inlets of the sub channels, outlets of the removal channels, outlets of the collection channels, and outlets of the main channels, which are provided in the micro-channel units, are connected to respective pillar channels penetrating each of layers in a traversing manner.