Microfluidic Alginate Microparticles for Size and Shape Control

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

It is challenging to produce hydrogel microparticles with defined shapes and sizes less than 50 μm and to control the distribution of crosslinking agents for structural homogeneity and reproducibility.

Innovation Solution

The development of microparticles using microfluidic techniques to form crosslinked gel microparticles with controlled size, shape, and morphology, including core-shell and Janus-type structures, using alginate and Ca2+-EDTA, with a coefficient of variation in size distribution from 0.03 to 0.05, allowing for encapsulation of cells and active agents.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If conventional gelation methods are used to form microparticles, then the process is simple, but the microparticles cannot achieve defined shapes and sizes less than 50 μm with high monodispersity

Engineering Contradiction:

Improvemicroparticle size and shape controlVSAvoidmicrofluidic device complexity

Core Design Contradiction:

Manufacturing precisionVSDevice complexity

Solution Approach 1:

The invention segments the gelation process into distinct microfluidic stages: droplet formation with controlled size, crosslinking agent introduction, and gelation. This segmentation enables precise control over microparticle dimensions (achieving <50 μm with CV<0.05) and shape while using standardized microfluidic components

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The invention transitions from conventional bulk gelation to microfluidic droplet-based gelation, adding the dimension of precise flow control and interfacial reaction. This dimensional shift enables defined shapes (spheres, rods, crescents) and sizes <50 μm that are inaccessible through traditional methods

Inventive Principle:

Principle #17Another dimension (Dimensionality change)

2Stability of the object's composition

If crosslinking agents are added to form gel microparticles, then gelation occurs, but the distribution of crosslinking agent cannot be controlled for structural homogeneity

Engineering Contradiction:

Improvecrosslinking agent distribution homogeneityVSAvoidstructural homogeneity

Core Design Contradiction:

Stability of the object's compositionVSManufacturing precision

Solution Approach 1:

The crosslinking agent is pre-introduced into the droplet along with the polymer solution before gelation begins. This preliminary action ensures uniform distribution of the crosslinking agent throughout the droplet volume, leading to homogeneous gel structure and consistent mechanical properties

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The microfluidic system maintains homogeneous mixing of polymer and crosslinking agent within each droplet through controlled flow rates and rapid mixing at the junction. This homogeneity principle ensures uniform crosslinking density throughout the microparticle structure

Inventive Principle:

Principle #33Homogeneity

3Manufacturing precision

If microparticle size is reduced to less than 50 μm, then higher monodispersity is achieved, but production difficulty increases significantly

Engineering Contradiction:

Improvesize monodispersityVSAvoidproduction ease

Core Design Contradiction:

Manufacturing precisionVSEase of manufacture

Solution Approach 1:

The invention replaces mechanical size control methods (screening, filtration, centrifugation) with flow-based microfluidic control. The droplet size is determined by flow rates and channel geometry rather than mechanical separation, enabling <50 μm particles with CV<0.05 to be produced directly in a single step

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

4Manufacturing precision

If defined shapes and sizes are achieved through microfluidic techniques, then manufacturing precision improves, but device complexity increases

Engineering Contradiction:

Improvemicroparticle geometry controlVSAvoidmicrofluidic channel design

Core Design Contradiction:

Manufacturing precisionVSDevice complexity

Solution Approach 1:

The microfluidic device uses universal T-junction or flow-focusing geometries that can produce multiple shapes (spheres, rods, crescents) by simply adjusting flow rates and channel dimensions. This multi-functionality reduces the need for complex dedicated fixtures for each particle geometry

Inventive Principle:

Principle #6Universality (Multi-functionality)

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 enables the creation of monodisperse, structurally homogeneous microparticles suitable for various applications, including pharmaceuticals, cosmetics, and tissue engineering, with improved drug delivery and regenerative medicine capabilities, and enhanced biological accuracy in cell-based tests.

Implementation Method 1

Microfluidic techniques can be used to prepare rods, crescents, hooks, as well as core-shell microparticles

Methodology Applied

Scientific EffectInterfacial tension: Surface Tension

Implementation Method 2

using alginate and Ca2+-EDTA, with a coefficient of variation in size distribution from 0.03 to 0.05

Methodology Applied

Scientific EffectIon exchange: Ion Exchange

Implementation Method 3

encapsulation of cells and active agents

Methodology Applied

Scientific EffectPhysical containment: Physical Containment

Data Source

PatentUS10471016B2Microparticles, methods for their preparation and use

Publication Date: 2019.11.12 PRESIDENT & FELLOWS OF HARVARD COLLEGE

AI summary

The invention relates to microparticles comprising a crosslinked gel and methods for making and using same.