Microfluidic Chip eDAR Sorting Rare Cells
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Solution Overview
Problem
Current methods for isolating rare cells from fluid samples, such as circulating tumor cells, face challenges in achieving high purity and efficiency, often resulting in low recovery rates and high false positive rates.
Innovation Solution
The use of Ensemble Decision Aliquot Ranking (eDAR) combined with microfluidic technologies, including hydrodynamic sorting and filtration, to enhance the separation and purification of rare cells by employing flow stretching and cell stretching operations, and microfluidic chips with specialized structures like herringbone mixers and microslits, allowing for efficient sorting and collection of rare cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If traditional isolation methods are used for rare cells, then the process is simple, but the purity of isolated rare cells is low
Solution Approach 1:
The system divides the fluid sample into multiple discrete aliquots and processes them sequentially through the microfluidic chip. Each aliquot is individually analyzed and sorted, enabling precise control over the isolation process and achieving high purity without requiring overly complex bulk separation mechanisms.
Solution Approach 2:
The invention integrates multiple functional components within a single microfluidic chip, including hydrodynamic sorting structures, filtration elements (microslits), and collection chambers. This nested integration allows complex separation and purification functions to be achieved within a compact device structure.
2Productivity
If traditional isolation methods are used for rare cells, then the equipment is simple, but the recovery rate is low
Solution Approach 1:
The system performs preliminary enrichment of rare cells through hydrodynamic sorting before final collection. The microfluidic structures pre-concentrate target cells in specific flow regions, ensuring high recovery rates while maintaining a relatively simple overall device architecture.
Solution Approach 2:
The invention introduces buffer fluids as intermediary substances to facilitate cell separation. Buffered saline solutions are used to control hydrodynamic flow, enable pressure-driven sorting, and maintain cell viability throughout the isolation process, improving recovery without adding mechanical complexity.
3Reliability
If traditional isolation methods are used for rare cells, then the process is fast, but the false positive rate is high
Solution Approach 1:
The microfluidic chip incorporates localized filtration structures (microslits with specific dimensions) at critical positions within the flow path. These localized features provide precise size-based filtering to distinguish target rare cells from larger contaminating cells, reducing false positives without requiring system-wide complexity.
Solution Approach 2:
The invention replaces complex mechanical sorting systems with passive hydrodynamic sorting based on cell size and flow dynamics. The microfluidic structures exploit natural fluid mechanics and cell physical properties to achieve accurate separation, improving reliability while maintaining device simplicity.
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 significantly enhances the purity of isolated rare cells by up to 30 times compared to traditional methods, with high recovery ratios and low false positive rates, enabling effective diagnosis and prognosis in various biological applications.
Implementation Method 1
The flow stretching is imparted by parabolic flow of the first isolated sample through a flow path
Implementation Method 2
The flow stretching is imparted by herringbone mixing of the first isolated sample
Implementation Method 3
the barrier comprises a filter structure, a constriction of the channel, or a weir structure
Implementation Method 4
dispersing the first isolated sample comprises cell stretching of the first isolated sample
Implementation Method 5
the first interaction is selected from the group consisting of: optical reflection, optical transmission, elastic optical scattering, inelastic optical scattering, Rayleigh scattering, Raman scattering, surface-enhanced Raman scattering, Mie scattering, Brillouin scattering, fluorescence, autofluorescence, laser-induced fluorescence, luminescence, bioluminescence, and chemiluminescence
Implementation Method 6
the first interaction is selected from the group consisting of: optical reflection, optical transmission, elastic optical scattering, inelastic optical scattering, Rayleigh scattering, Raman scattering
Data Source
Figure 1A~1C
Figure 2
Figure 3A~3H
AI summary
Provided herein, among other aspects, are methods and apparatuses for analyzing particles in a sample. In some aspects, the particles can be analytes, cells, nucleic acids, or proteins and can be contacted with a tag, partitioned into aliquots, detected by a ranking device, and isolated. The methods and apparatuses provided herein may include a microfluidic chip. In some aspects, the methods and apparatuses may be used to quantify rare particles in a sample, such as cancer cells and other rare cells for disease diagnosis, prognosis, or treatment.