Microfluidic Particle Isolation via Image Subtraction

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Solution Overview

Problem

Microfluidic systems for particle manipulation and analysis face challenges such as incorrect identification and recognition of particles, suboptimal operating speed, and risk of particle damage or contamination, particularly in fluorescence-based imaging which is discontinuous and harmful to cells and DNA.

Innovation Solution

A microfluidic system with a moving assembly comprising actuators, a detection device, and a control device that acquires and processes images to move particles deterministically and selectively within a microfluidic chamber, using techniques like dielectrophoresis, optical tweezers, and image subtraction to enhance visibility and precision, reducing the need for fluorescence and minimizing particle loss or damage.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Illumination intensity

If fluorescence-based imaging is used to acquire images of particles, then particle visibility is improved, but particle damage and contamination risk increase

Engineering Contradiction:
Improveparticle visibilityVSAvoidparticle damage and contamination
Core Design Contradiction:
Illumination intensityVSObject-affected harmful factors

Solution Approach 1:

The patent replaces fluorescence-based optical imaging with label-free optical imaging techniques (such as differential interference contrast, phase contrast, or reflection imaging) that do not require fluorescent markers. This substitution eliminates the harmful effects of fluorescent dye phototoxicity and DNA damage while maintaining particle visibility through enhanced contrast methods that work with native particle properties.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent employs disposable microfluidic chips with integrated imaging chambers that eliminate the need for complex fluorescence setup and reduce contamination risk. The disposable nature ensures each chip is sterile and free from cross-contamination, while the simplified imaging system avoids the need for expensive fluorescent reagents and their associated handling risks.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

2Measurement precision

If fluorescence-based discontinuous imaging is used, then particle identification is achieved, but operating speed decreases

Engineering Contradiction:
Improveparticle identificationVSAvoidoperating speed
Core Design Contradiction:
Measurement precisionVSProductivity

Solution Approach 1:

The patent implements continuous label-free optical imaging throughout the particle manipulation process, eliminating the intermittent nature of fluorescence imaging. This continuous imaging approach allows real-time tracking and identification of particles at every stage of manipulation, significantly increasing operating speed while maintaining identification precision through advanced image processing algorithms.

Inventive Principle:
Principle #20Continuity of useful action

Solution Approach 2:

The patent performs preliminary particle characterization using label-free imaging before fluorescence staining is applied (or without staining entirely). This preliminary action enables early identification and sorting decisions to be made based on morphological features, size, and other native properties, accelerating the overall process by eliminating waiting time for fluorescence signal development and acquisition.

Inventive Principle:
Principle #10Preliminary action

3Speed

If conventional microfluidic systems are used for particle manipulation, then basic particle movement is achieved, but particle loss and damage occur

Engineering Contradiction:
Improveparticle manipulation capabilityVSAvoidparticle integrity
Core Design Contradiction:
SpeedVSReliability

Solution Approach 1:

The patent introduces a specially designed microfluidic environment with optimized channel geometries, surface coatings, and flow regimes that act as intermediaries between the manipulation forces and the particles. These intermediaries provide gentle, controlled manipulation through laminar flow and optimized shear stresses, preventing particle damage while enabling effective sorting and isolation. The microfluidic design incorporates features like gentle merging zones and optimized collection chambers that minimize mechanical stress on particles.

Inventive Principle:
Principle #24Intermediary (Mediator)

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 system improves particle identification, precision, and speed, reducing the risk of damage and contamination by providing continuous tracking and brighter, more precise images, allowing for efficient and selective manipulation and analysis of particles without the need for fluorescence, which is harmful and discontinuous.

Implementation Method 1

a detection device (7), which is configured to acquire images of the microfluidic chamber (4)

Methodology Applied
Scientific EffectOptical imaging: Light

Implementation Method 2

using techniques like dielectrophoresis, optical tweezers

Methodology Applied
Scientific EffectDielectrophoresis: Dielectric

Implementation Method 3

using techniques like dielectrophoresis, optical tweezers

Methodology Applied
Scientific EffectOptical tweezers: Optical Tweezers

Data Source

PatentUS20240216913A1Method and microfluidic system for the isolation of particles
Publication Date: 2024.07.04 MENARINI SILICON BIOSYSTEMS SPA
  • US20240216913A1 patent drawing
  • US20240216913A1 patent drawing
  • US20240216913A1 patent drawing

AI summary

Method and microfluidic system (1) for the manipulation of particles; a detection device (7) acquires images of a specific particle (5) in a first position (IP) and in a second position (IIP); the difference is made between the two images in order to obtain a derived image in which the contours and the morphological characteristics of the specific particle (5) are more evident; in this manner, the type and the position of the particles can be identified more clearly, continuously and in a time-saving manner.