Closed-Loop Microfluidic Cell Enrichment
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Solution Overview
Problem
Current methods for cell separation in biofluids face challenges in achieving high purity and recovery of rare cells, often compromising between these two factors, and require processing large volumes with minimal molecular background interference.
Innovation Solution
A closed-loop inertial microfluidic system with a spiral microchannel having a trapezoidal cross-section, allowing for recirculation of sample fluid and separation based on particle size and deformability, enabling efficient isolation and enrichment of rare cells by bifurcating streams and recirculating them for concentration and purification.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If inertial microfluidics is used for cell separation, then processing rate is improved, but purity and recovery of rare cells deteriorate
Solution Approach 1:
The patent implements a closed-loop recirculation system where the fluid continuously flows through the microchannel, allowing multiple separation passes without interrupting the process. This continuous action enables both high processing rates and improved purity/recovery by repeatedly exposing particles to the separation mechanism, accumulating rare cells over multiple cycles while maintaining steady-state flow conditions.
Solution Approach 2:
The system incorporates a feedback loop where separated particles are recirculated back through the microchannel. This feedback mechanism allows the system to continuously refine the separation process, with each pass improving the purity and recovery of rare cells while maintaining high processing throughput through automated continuous operation.
2Quantity of substance
If large volumes of biofluid are processed, then quantity of target cells is improved, but background interference worsens
Solution Approach 1:
The patent employs a microchannel with specifically designed geometry (non-rectangular cross-section with curved walls) that extracts or removes background molecules and non-target particles from the fluid stream through inertial focusing and Dean flow effects. This selective extraction allows processing of large volumes to recover sufficient target cells while actively removing background interference that would otherwise contaminate the sample.
Solution Approach 2:
The microchannel geometry creates localized flow patterns and inertial forces that selectively affect different particle sizes and densities. By optimizing the channel dimensions and curvature, the system creates local conditions that enhance separation of rare cells from background, allowing high-throughput processing with minimal contamination.
3Device complexity
If single-pass separation is used, then device complexity is reduced, but separation efficiency deteriorates
Solution Approach 1:
The patent merges the separation and concentration functions into a single integrated microfluidic device with a closed-loop configuration. By combining multiple separation passes within one continuous flow path and using the recirculation loop to concentrate particles, the system achieves high separation efficiency without requiring multiple separate devices or complex multi-stage processing systems.
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 achieves high recovery and purity of target cells, minimizing background interference and allowing for continuous processing of large volumes, suitable for downstream assays like ELISA and PCR, with over 95% cell recovery and 97.7% viability.
Implementation Method 1
the field of inertial microfluidics has shown promise for in separating cells from a biofluid with high processing rates
Implementation Method 2
one being the net lift force and the other being the Dean drag force
Implementation Method 3
one being the net lift force and the other being the Dean drag force
Data Source
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AI summary
The present invention encompasses a micro-fluidic system having a closed-loop configuration in which inertial micro-fluidic separation of particles and/or cells is continuously repeated by feeding part of the output back to the input so that the purity and/or concentration of the particles and/or cell is maximized. The invention also includes methods of using the micro-fluidic system.