Hydrodynamic Particle Separation Using Cylindrical Illumination

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Solution Overview

Problem

Conventional methods for DNA sizing and separation, such as electrophoresis and capillary electrophoresis, face limitations including poor resolution, high costs, and sensitivity to capillary wall properties, making them inefficient for accurately sizing and separating DNA molecules across a wide dynamic range.

Innovation Solution

A hydrodynamic system that uses cylindrical illumination confocal spectroscopy (CICS) integrated with free solution hydrodynamic separation (FSHS), allowing for size-specific single molecule analysis, where particles are separated based on their travel time through a fluid channel, enabling high sensitivity and resolution without the need for expensive instrumentation or complex sieving matrices.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If capillary electrophoresis is used for high-resolution DNA separation, then DNA sizing resolution and detection sensitivity are improved, but device complexity and instrumentation cost increase

Engineering Contradiction:

ImproveDNA sizing resolutionVSAvoidinstrumentation complexity

Core Design Contradiction:

Measurement precisionVSDevice complexity

Solution Approach 1:

The patent extracts and eliminates the complex sieving matrices and functionalized capillary walls from the system, achieving separation through pure hydrodynamic principles in a simple fluid channel, thereby reducing device complexity while maintaining resolution

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent replaces the electrical field-based capillary electrophoresis system with a hydrodynamic flow-based system, substituting mechanical fluid flow for electrical separation mechanisms, which simplifies the instrumentation requirements

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

2Measurement precision

If capillary electrophoresis with laser-induced fluorescence detection is used, then detection sensitivity is improved, but mass detection efficiency decreases due to detection zone limitations

Engineering Contradiction:

Improvedetection sensitivityVSAvoidmass detection efficiency

Core Design Contradiction:

Measurement precisionVSReliability

Solution Approach 1:

The patent transitions from point-based detection to line-based detection by illuminating the entire cross-section of the fluid channel, effectively adding a spatial dimension to detection that captures all particles passing through the channel regardless of position

Inventive Principle:

Principle #17Another dimension (Dimensionality change)

3Productivity

If conventional electrophoresis methods are used, then DNA separation is achieved, but quantitative accuracy and reproducibility deteriorate due to sensitivity to capillary wall properties

Engineering Contradiction:

Improveseparation capabilityVSAvoidquantitative accuracy

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The patent removes the capillary wall functionalizations and sieving matrices that cause reproducibility issues, achieving separation through hydrodynamic principles alone that are independent of wall properties, thereby improving quantitative accuracy and reliability

Inventive Principle:

Principle #2Taking out (Extraction)

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 provides high sensitivity, resolution, and a wide dynamic range for DNA sizing, achieving 100% mass detection efficiency with minimal sample consumption, surpassing the performance of traditional methods like capillary electrophoresis and gel electrophoresis.

Implementation Method 1

compelling the fluid to flow through a fluid channel such that larger particles of the plurality of particles travel through the fluid channel faster than smaller particles of the plurality of particles

Methodology Applied

Scientific EffectHydrodynamic separation:

Implementation Method 2

illuminating a detection zone of the fluid channel substantially uniformly across an entire cross section of the fluid channel such that each of the plurality of particles passes through illumination light

Methodology Applied

Scientific EffectCylindrical illumination:

Implementation Method 3

detecting each of the plurality of particles based on corresponding responses to the illuminating to determine a time that each of the plurality of particles passes through the detection zone

Methodology Applied

Scientific EffectLight scattering/absorption: Absorption (EM radiation)

Data Source

PatentUS9476819B2Hydrodynamic particle separation and detection systems and methods

Publication Date: 2016.10.25 JOHNS HOPKINS UNIVERSITY

AI summary

A method of separating, detecting and determining a size of each of a plurality of particles in a fluid includes compelling the fluid to flow through a fluid channel such that larger particles of the plurality of particles travel through the fluid channel faster than smaller particles of the plurality of particles; illuminating a detection zone of the fluid channel substantially uniformly across an entire cross section of the fluid channel such that each of the plurality of particles passes through illumination light upon passing through the detection zone; detecting each of the plurality of particles based on corresponding responses to the illuminating to determine a time that each of the plurality of particles passes through the detection zone; and determining a size of each of the plurality of particles based on the time that each of the plurality of particles passes through the detection zone.