Cavity Microparticles for Uniform Droplet Encapsulation

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Solution Overview

Problem

Current droplet-based systems for forming monodisperse emulsions with solid-phase particles face challenges in achieving uniform droplet size and volume, particularly when encapsulating cells or large molecules, due to the stochastic nature of particle encapsulation and limited space within the droplets.

Innovation Solution

The use of cavity-containing microparticles as templates to generate uniform droplets, which provide an open space for reactions and encapsulation, enhancing the volume of aqueous fluid samples and improving the uniformity of droplet formation by controlling microparticle shape and void design.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If simple agitation (vortexing/pipetting) of aqueous phase containing dispersed particles into oil water suspension is used, then droplet formation is achieved, but large variations in droplet volume and poor monodispersity occur

Engineering Contradiction:
Improvedroplet volume uniformityVSAvoidoperation complexity
Core Design Contradiction:
Manufacturing precisionVSEase of operation

Solution Approach 1:

The patent applies preliminary action by pre-forming particles with controlled sizes and shapes (including hollow or porous structures) before the droplet formation process. These pre-engineered particles serve as templates that dictate uniform droplet volumes during subsequent agitation-based emulsification, eliminating the need for complex microfluidic devices while achieving monodisperse droplets.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent employs parameter changes by systematically varying particle properties (size, shape, porosity, hollow vs. solid structure) to control droplet formation outcomes. By adjusting these particle parameters, the invention achieves uniform droplet volumes through simple agitation methods, transforming the relationship between particle characteristics and droplet properties.

Inventive Principle:
Principle #35Parameter changes

2Volume of moving object

If particles are used as templates to define minimum droplet size, then droplet size control is achieved, but the thin fluid layer around particles provides no space for encapsulation of microscale objects

Engineering Contradiction:
Improveencapsulable volumeVSAvoiddroplet size uniformity
Core Design Contradiction:
Volume of moving objectVSManufacturing precision

Solution Approach 1:

The patent utilizes porous materials by incorporating porous particles as templates for droplet formation. The porous structure provides internal void space within the particle itself, creating additional encapsulation volume beyond the thin external fluid layer. This allows microscale objects to be encapsulated within the porous matrix while maintaining uniform external droplet dimensions.

Inventive Principle:
Principle #31Porous materials

Solution Approach 2:

The patent applies the nesting principle by creating hierarchical structures where microscale objects (cells, beads) are encapsulated within the porous interior of particles, which themselves are embedded in the droplet matrix. This nested arrangement maximizes usable volume while maintaining compact droplet sizes and uniform geometry.

Inventive Principle:
Principle #7Nested doll (Nesting)

3Manufacturing precision

If stochastic processes of particle encapsulation are used, then particle distribution occurs, but achieving single particle per droplet is challenging

Engineering Contradiction:
Improveparticle distribution uniformityVSAvoidparticle concentration control
Core Design Contradiction:
Manufacturing precisionVSQuantity of substance

Solution Approach 1:

The patent applies preliminary action by pre-sorting and pre-distributing particles into defined spatial arrangements before droplet formation. This pre-organization ensures that each particle occupies a specific position that corresponds to a future droplet location, eliminating stochastic distribution and guaranteeing single-particle-per-droplet encapsulation.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent employs segmentation by dividing the particle suspension into discrete, spatially separated particle positions before emulsification. This segmentation prevents particle aggregation and ensures that each droplet receives exactly one particle, transforming the random stochastic process into a controlled deterministic distribution.

Inventive Principle:
Principle #1Segmentation

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 results in significantly improved uniformity and increased encapsulation efficiency of aqueous fluid samples, allowing for effective cell culture, analysis, and reactions within the droplets, while maintaining cell viability and enabling high-throughput sorting and analysis.

Implementation Method 1

The particles contained in the droplets can act as templates to define a minimum droplet size

Methodology Applied
Scientific EffectCapillary action: Capillary Action

Implementation Method 2

droplets were formed using simple agitation (vortexing/pipetting) of an aqueous phase containing dispersed particles into an oil water suspension

Methodology Applied
Scientific EffectSurface tension: Surface Tension

Implementation Method 3

The use of microparticles which contain a void or cavity region connected to or in communication with the particle surface can act as significantly improved particle templates to generate a uniform distribution of droplets while also containing an open space to perform reactions or encapsulate cells, beads, and other small micro-objects

Methodology Applied
Scientific EffectPhysical containment: Physical Containment

Implementation Method 4

WO 2004/103351 A1 discloses a droplet-based system comprising three-dimensional hydrophilic drop-carrier particles formed from a crosslinked hydrogel, each hydrophilic drop-carrier particle having a void formed therein; an aqueous fluid associated with the hydrophilic drop-carrier particles, the hydrophilic drop-carrier particles associated with the aqueous fluid being disposed or suspended in an oil phase

Methodology Applied
Scientific EffectEmulsion: Emulsion

Data Source

PatentEP3836887B1Particle-containing droplet systems with monodisperse fluid volumes
Publication Date: 2024.07.17 RGT UNIV OF CALIFORNIA
  • EP3836887B1 patent drawingFigure 1A~1B
  • EP3836887B1 patent drawingFigure 2
  • EP3836887B1 patent drawingFigure 3

AI summary

Systems and methods are described herein that create discrete volumes associated with solid-phase particles (e.g., drop-carrier particles) suspended in an immiscible phase (e.g., dropicles). One embodiment of the system includes a plurality of hydrogel-based drop-carrier particles containing a microscale voids or cavities that hold an aqueous phase droplet of fluid within each drop-carrier particle. The plurality of hydrogel drop-carrier particles associated with aqueous drops are suspended as individual elements in an immiscible oil phase. The microscale hydrogel drop-carrier particles containing the voids or cavities may be manufactured using microfluidic droplet generators. The dropicles may be used to analyze single-entities (e.g., single-molecules and single-cells) and analytes.