Mono-disperse Particle Production via Microfluidic Emulsion and Filtration

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Solution Overview

Problem

Existing methods for producing mono-disperse particles are inefficient and wasteful, particularly when dealing with valuable pharmaceuticals or biotechnological products, as they often result in particles that are either too large and block capillaries or too small and are systematically lost.

Innovation Solution

A method involving the formation of an emulsion of micro-droplets using a micro-channel device with a channel plate and secondary channels, followed by solvent evaporation to create microspheres, and subsequent filtration through a micro-filter with a narrow pore size distribution to achieve a mono-disperse particle size distribution.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If conventional methods are used to produce particles, then particle production is achieved, but particle size distribution is broad and includes particles that are too large or too small

Engineering Contradiction:
Improveparticle size distributionVSAvoidwaste of valuable pharmaceuticals
Core Design Contradiction:
Manufacturing precisionVSLoss of substance

Solution Approach 1:

The invention segments the particle production process into controlled micro-environments using microfluidic devices with multiple channels of specific geometries. Each micro-channel creates discrete droplets that evolve into individual particles, ensuring uniform size distribution and eliminating the need to discard oversized or undersized particles.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention changes physical parameters including micro-channel geometry (width, depth, length), flow rates of first and second fluids, and secondary channel configurations to precisely control droplet size and particle formation. These parameter adjustments enable production of mono-disperse particles with narrow size distribution centered on a target size.

Inventive Principle:
Principle #35Parameter changes

2Reliability

If particles are made larger to ensure delivery to target site, then delivery efficacy is improved, but particles may block capillaries causing macro-infarcts

Engineering Contradiction:
Improvedelivery efficacyVSAvoidcapillary blockage
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The invention applies local quality by creating particles with precisely controlled uniform sizes tailored to specific delivery requirements. Different micro-channel geometries and flow conditions produce particles optimized for specific capillary bed targets, ensuring each particle is large enough for effective delivery but small enough to pass through target capillaries without blockage.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The invention replaces conventional mechanical mixing and emulsification methods with microfluidic-based droplet generation. This substitution provides precise control over particle size and distribution, eliminating the broad size ranges that lead to capillary blockage while maintaining delivery efficacy.

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

3Ease of operation

If particles are made smaller to pass through capillaries, then capillary passage is improved, but particles are systematically lost and do not reach target site

Engineering Contradiction:
Improvecapillary passageVSAvoidsystematic loss of particles
Core Design Contradiction:
Ease of operationVSLoss of substance

Solution Approach 1:

The invention performs preliminary action by pre-determining the optimal particle size for each specific delivery scenario through careful selection of micro-channel dimensions and flow parameters. This preliminary optimization ensures particles are sized correctly before administration, preventing both capillary blockage and systematic loss, and maximizing particle delivery to the target site.

Inventive Principle:
Principle #10Preliminary action

4Productivity

If conventional emulsification methods are used, then particle formation is achieved, but particle size distribution remains broad

Engineering Contradiction:
Improveparticle formation efficiencyVSAvoiddroplet size uniformity
Core Design Contradiction:
ProductivityVSManufacturing precision

Solution Approach 1:

The invention transitions from conventional bulk emulsification to microfluidic-based droplet generation, adding the dimension of spatial confinement through micro-channels. This dimensional change enables precise control over droplet formation and size, producing uniform particles while maintaining high production efficiency through continuous flow processes.

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

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 method effectively produces particles with an extremely narrow size distribution, ensuring that no particles exceed a maximum allowable size, thereby minimizing waste and maximizing efficacy for local drug delivery applications.

Implementation Method 1

dispersing said first fluid in at least one second fluid to form an emulsion of micro droplets of said first fluid in a second fluid

Methodology Applied
Scientific EffectEmulsion: Emulsion

Implementation Method 2

allowing said micro droplets of said first fluid to lose said solvent in said second fluid and to form microspheres containing said substance

Methodology Applied
Scientific EffectEvaporation: Evaporation

Implementation Method 3

subjecting said second fluid containing said microspheres to a micro filter having a relatively narrow pore size distribution around an average pore size

Methodology Applied
Scientific EffectFiltration: Filter (physical)

Data Source

PatentEP3612164B1Method and system for producing substantially mono-disperse particles of a substance
Publication Date: 2025.04.09 NANOMI BV
  • EP3612164B1 patent drawingFigure 1~3
  • EP3612164B1 patent drawingFigure 4A~4B
  • EP3612164B1 patent drawingFigure 5

AI summary

A first fluid is dispersed in a second fluid to form an emulsion of micro-droplets having an average droplet size and having a droplet size distribution around said average droplet size and below a maximum droplet size. Said micro-droplets will lose their solvent to transform to micro-spheres exhibiting a particle size distribution around an average particle size and substantially below a maximum allowable particle size. Said micro-spheres are subjected to a micro-filter having a relatively narrow pore size distribution around an average pore size, which average pore size is between said average particle size and said maximum particle size. A filtrate of said micro-filter comprises a majority of said micro-spheres that is substantially void of micro-spheres having a particle size exceeding the maximum allowable particle size.