Macroporous Polymeric Hydrogel Microparticles Fabrication

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Current methods for fabricating polymeric hydrogel microparticles are either non-uniform due to batch processes or require complex and non-scalable microfluidics for macroporous structures, and often compromise mechanical integrity and uniformity.

Innovation Solution

A method involving a 2D-shaped PDMS micromold and UV-induced radical polymerization of an aqueous pre-polymer solution containing acrylamide, bisacrylamide, and chitosan, with a poly(ethylene glycol) porogen, to produce highly uniform and macroporous polymeric hydrogel microparticles capable of rapid biomolecule conjugation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If batch processes using dispersion or emulsion polymerization are used to fabricate polymeric hydrogel microparticles, then the fabrication process is simple and scalable, but the microparticles are polydisperse and non-uniform

Engineering Contradiction:
Improvefabrication process simplicityVSAvoidmicroparticle uniformity
Core Design Contradiction:
Ease of manufactureVSManufacturing precision

Solution Approach 1:

The patent replaces traditional mechanical mixing and batch polymerization methods with a microfluidics-based continuous flow system. This substitution enables precise control over microparticle formation, resulting in monodisperse uniform microparticles while maintaining scalability through continuous processing

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

Solution Approach 2:

The patent employs parameter changes by controlling flow rates, residence times, and temperature profiles in the microfluidic system to achieve uniform microparticle formation. By precisely adjusting these parameters, the process produces monodisperse particles while maintaining ease of manufacture through automated continuous operation

Inventive Principle:
Principle #35Parameter changes

2Manufacturing precision

If microfluidics-based techniques are used to fabricate highly uniform hydrogel microparticles, then microparticle uniformity is improved, but the devices are complex and not scalable to produce macroporous structures

Engineering Contradiction:
Improvemicroparticle uniformityVSAvoidmicrofluidic device complexity
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The patent segments the microfluidic device into modular components including separate channels for monomer delivery, photoinitiator incorporation, and patterned micromold integration. This segmentation simplifies device fabrication and enables scalability while maintaining uniform microparticle production through standardized modular units

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent introduces a photoinitiator as an intermediary substance that enables UV-induced polymerization within the microfluidic channels. This intermediary allows the process to proceed with simpler device architecture by using light activation rather than requiring complex temperature or pressure control systems, thereby reducing device complexity while maintaining scalability

Inventive Principle:
Principle #24Intermediary (Mediator)

3Shape

If various porogens are used to fabricate hydrogel microparticles with macroporous structures, then porosity is improved, but the network structures become non-uniform and mechanical integrity is compromised

Engineering Contradiction:
Improvemacroporous structureVSAvoidnetwork structure uniformity
Core Design Contradiction:
ShapeVSManufacturing precision

Solution Approach 1:

The patent incorporates porogens into the monomer solution before microfluidic processing, performing the porogen incorporation action in advance. This preliminary action ensures uniform distribution of porogens throughout the monomer feed, which then translates to uniform macroporous network structures in the final microparticles without compromising mechanical integrity

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent uses a universal porogen system that can be integrated into the microfluidic process without requiring separate porogen addition steps. The porogen serves multiple functions: creating macropores, maintaining network uniformity, and preserving mechanical integrity, thereby achieving macroporous structures with high precision through a single integrated approach

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

Facile fabrication of uniform polymeric hydrogel microparticles with controlled macroporous structures and rapid biomolecule conjugation, achieving high selectivity and minimal nonspecific binding, suitable for biomedical applications.

Implementation Method 1

inducing radical polymerization by exposing the aqueous pre-polymer solution to UV light for 0.25 to 1 hour to produce a 2D shape-encoded polymeric hydrogel microparticle formed of polyacrylamide and chitosan

Methodology Applied
Scientific EffectRadical polymerization: Photopolymerisation

Implementation Method 2

The chitosan in the microparticle, uniformly incorporated in a polyacrylamide matrix, typically has an average molar mass of 4,500-200,000 Da (e.g., 5,000 Da). It contains primary amines having a pKa value of 6.0-6.9 (e.g., 6.5), which are capable of conjugating to biomolecules via an acyl or nucleophilic substitution reaction.

Methodology Applied
Scientific EffectNucleophilic substitution: Chemical Bonding

Data Source

PatentUS11298678B2Fabrication of macroporous polymeric hydrogel microparticles
Publication Date: 2022.04.12 TRUSTEES OF TUFTS COLLEGE

AI summary

A polymeric hydrogel microparticle that contains polyacrylamide and chitosan, the chitosan uniformly incorporated in a polyacrylamide matrix. The microparticle, having a coefficient variation of 0 to 2% and containing macropores with an average size of 1 to 60 nm, is capable of transporting biomolecules conjugated to it. Also disclosed are a method of fabricating such a microparticle in a micromold via photo-induced radical polymerization and a one-pot method of conjugating biomolecules to polymeric hydrogel microparticles.