Sheath Flow Device for Reducing Non-Specific Binding in Microfluidic Sorting

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Solution Overview

Problem

Current particle sorting technologies face challenges in minimizing contamination and non-specific binding, particularly in microfluidic devices, where rare cells need to be sorted from complex samples, and existing methods for establishing laminar sheath flow are complex and difficult to manufacture.

Innovation Solution

A sheath flow device is designed with laminar buffer and sample flows establishing parallel surfaces, creating a sheath flow plane that prevents turbulent flow and non-specific binding, using a configuration of parallel plates to maintain separate laminar flow planes and employing magnetic forces for particle separation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional flow cytometry devices are used to sort particles, then particle sorting can be achieved, but the device complexity and manufacturing difficulty increase significantly

Engineering Contradiction:
Improveparticle sorting capabilityVSAvoidinstrumentation complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The device is divided into distinct functional modules: a body portion containing fluidic channels, a cover portion with magnetic elements, and separate inlet/outlet ports. This segmentation allows each component to be optimized independently and simplifies manufacturing while maintaining sorting functionality.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention uses fluid flow (hydraulics) to transport particles through the device and employs magnetic fields generated by permanent magnets to deflect and sort magnetic particles. This combination of fluidic and magnetic forces enables sorting without complex mechanical moving parts.

Inventive Principle:
Principle #29Pneumatics and hydraulics

2Measurement precision

If hydrodynamic focusing is used to transport target moieties, then sorting specificity improves, but the device architecture becomes more complex

Engineering Contradiction:
Improvesorting specificityVSAvoiddevice architecture
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The invention extracts the focusing function from complex multi-channel hydrodynamic systems and implements it through a single V-shaped groove geometry that naturally focuses particles into a narrow stream using simple wall effects and flow dynamics.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The V-shaped groove uses curved geometry to guide and focus the fluid stream containing particles. The angled walls of the groove create a converging flow path that naturally focuses particles without requiring additional focusing channels or complex architectures.

Inventive Principle:
Principle #14Spheroidality (Curvature)

3Productivity

If particles flow in suspension along a horizontal fluid flow plane, then throughput is maintained, but particles may sink to the bottom and form barriers clogging the flow path

Engineering Contradiction:
ImprovethroughputVSAvoidflow path continuity
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The invention transitions from horizontal flow to vertical flow through the V-shaped groove. Particles are carried upward against gravity by the fluid flow, preventing them from settling on the bottom surface and forming clogs, while maintaining continuous throughput.

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

Solution Approach 2:

The flow direction parameter is changed from horizontal to vertical, and the flow velocity is optimized to exceed the settling velocity of particles. This parameter change ensures particles remain suspended and transported through the device without clogging.

Inventive Principle:
Principle #35Parameter changes

4Object-affected harmful factors

If surface coatings are applied to minimize non-specific binding, then binding reduction is achieved, but the complexity and cost of device fabrication increase

Engineering Contradiction:
Improvenon-specific bindingVSAvoidfabrication simplicity
Core Design Contradiction:
Object-affected harmful factorsVSEase of manufacture

Solution Approach 1:

Instead of trying to prevent non-specific binding through complex coatings, the invention uses the vertical flow geometry to physically separate particles from surface contact areas. The flow path is designed so particles pass through regions away from channel walls, converting the potential harm of non-specific binding into a benefit by eliminating surface interactions through geometric design.

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

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 device effectively reduces non-specific binding and contamination, enabling efficient sorting and detection of rare cells by maintaining laminar flow and using magnetic forces for targeted separation, improving sensitivity and throughput in microfluidic applications.

Implementation Method 1

a first laminar buffer flow establishing surface upstream of a sheath flow plane area; a sample laminar flow establishing surface parallel to the sheath flow plane area

Methodology Applied
Scientific EffectLaminar flow: Laminar Flow

Implementation Method 2

a particle sorting station configured to deflect a target species from a sample laminar flow, wherein the station employs a magnetic force and is adapted for magnetophoretic particle separation

Methodology Applied
Scientific EffectMagnetic force: Magnetic Field

Data Source

PatentEP2440941B1Sheath flow devices and methods
Publication Date: 2017.05.31 CYNVENIO BIOSYST INC
  • EP2440941B1 patent drawingFigure 1
  • EP2440941B1 patent drawingFigure 2A~2B
  • EP2440941B1 patent drawingFigure 2C

AI summary

The invention relates generally to fluid processing and, in particular aspects, processing fluids for detection, selection, trapping and/or sorting of particulate moieties. Sheath flow devices described allow isolation of target species from fluid samples while avoiding non-specific binding of unwanted species to the surfaces of the separation device. Biological fluid processing, detection, sorting or selection of cells, proteins, and nucleic acids is described. The invention finds particular use in diagnostic settings, analyzing a patient's medical condition, monitoring and/or adjusting a therapeutic regimen and producing cell based products.