Microfluidic Particle Sorter Using Segmented DLD Pillars
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Solution Overview
Problem
Current methods for sorting circulating tumor cells (CTCs) using deterministic lateral displacement (DLD) face challenges such as low purity, high cost due to antibody usage, and inability to separate white blood cells with similar particle sizes, as well as high shear stress and low flow rates in sample fluids.
Innovation Solution
A microfluidic particle sorter with a chip body containing DLD arrays, where first and second DLD columns are offset to create micro-gaps that guide non-target particles away from the collection area, allowing target particles to be sorted efficiently while maintaining high purity and reducing the need for extensive fluid dilution.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If DLD arrays with pillars are used to separate target and non-target particles, then sorting efficiency is improved, but particles with similar sizes cannot be separated effectively
Solution Approach 1:
The pillars are segmented into two parts connected by a bridge, creating a gap structure that allows differential passage of particles based on size. This segmentation enables the DLD array to distinguish between particles of similar sizes by allowing smaller non-target particles to pass through the gap while retaining larger target particles.
Solution Approach 2:
The gap structure introduces a local structural variation in the DLD array, where the bridge-connected pillars create a specific zone with different flow characteristics. This local quality change enables selective particle separation based on size differences, improving the precision of particle size separation.
2Quantity of substance
If filtration process is used to capture CTCs, then CTC recovery is improved, but purity decreases due to capture of mutant cells and CTC clusters
Solution Approach 1:
The invention changes the separation parameter from physical filtration (which captures all particles above a certain size) to gap-based deterministic lateral displacement. By adjusting the gap size and pillar arrangement, the system can selectively pass non-target particles while retaining target particles, achieving both high recovery and high purity.
3Productivity
If positive selection with anti-EpCAM antibodies is used, then CTC sorting is improved, but some CTCs with low antigen expression are missed
Solution Approach 1:
The invention replaces the biochemical selection mechanism (antibody-antigen binding) with a physical separation mechanism based on deterministic lateral displacement through gap structures. This mechanical/physical approach separates particles based on size and shape differences, capturing all CTCs regardless of antigen expression levels.
4Productivity
If negative selection with anti-CD45/CD14 antibodies is used, then non-target cell removal is improved, but certain cancer cells expressing these markers are also removed
Solution Approach 1:
The invention replaces biochemical negative selection with a physical size-based separation mechanism. By using gap structures in the DLD array, the system removes non-target cells based on their size characteristics without relying on surface markers, thereby preserving cancer cells that may express CD45/CD14 markers.
5Quantity of substance
If filtration is used to capture CTCs, then CTC recovery is improved, but cell viability decreases due to high shear stress
Solution Approach 1:
The invention replaces high-shear stress filtration with a low-shear stress deterministic lateral displacement mechanism. The gap structures guide particle separation through flow dynamics rather than physical straining, significantly reducing shear stress exposure and preserving cell viability while maintaining high recovery rates.
6Manufacturing precision
If dielectrophoresis-based microfluidic chip is used, then CTC purity is improved, but sample fluid flow rate decreases and requires extensive dilution
Solution Approach 1:
The invention replaces dielectrophoresis (an electrical field-based mechanism requiring low ionic concentration and extensive dilution) with a passive deterministic lateral displacement mechanism based on flow dynamics and gap structures. This allows sorting to be performed on undiluted or minimally diluted samples at higher flow rates while maintaining high purity.
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 microfluidic particle sorter effectively separates target and non-target particles by DLD, achieving high recovery rates and purity of CTCs while avoiding the limitations of existing methods, including cost and shear stress issues, and enabling efficient sorting of particles with similar sizes.
Implementation Method 1
The microfluidic particle sorter is for sorting target particles and non-target particles in a sample fluid by deterministic lateral displacement (DLD)
Data Source
AI summary
A microfluidic particle sorter includes a chip body and at least one sorting unit provided inside the chip body and including a microfluidic channel and at least one first DLD array. The microfluidic channel extends along a length direction, has an inlet and an outlet, and has a first side and a second side. The at least one first DLD array includes first DLD columns arranged along the length direction. The first DLD columns, from the inlet toward the outlet, are gradually shifted toward the second side such that two adjacent ones of the first DLD columns are offset from each other by a predetermined distance. Each of the first DLD columns has first split pillars. Each of the first split pillars has a first upstream side and a first downstream side, and includes two first parts that are spaced apart from each other to define a first micro-gap.