Monodisperse Hydrogel Polymer Particles Through Two-Stage Polymerization

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Solution Overview

Problem

Existing methods for producing monodisperse polymeric particles, particularly those that are magnetic or coated, face challenges in controlling particle size variation, porosity, and hydrophobicity, which affect their suitability for biological applications.

Innovation Solution

A novel process using hydrophilic oligomer seed particles and a two-stage polymerization method to create monodisperse, cross-linked polymer particles that can be made magnetic and coated, with a low coefficient of variation, by incorporating magnetic material into the particles' pores and applying a coating.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If emulsion polymerisation is used to form monodisperse polymer particles, then relatively monodisperse particles of 50-1,000 nm can be produced, but the particles are either not crosslinked or have very low crosslinking levels because higher crosslinking prevents particle swelling

Engineering Contradiction:
Improveparticle size uniformityVSAvoidcrosslinking level
Core Design Contradiction:
Manufacturing precisionVSStability of the object's composition

Solution Approach 1:

The patent applies preliminary action by first forming monodisperse seed particles through emulsion polymerization, then using these seeds as templates for subsequent swelling and crosslinking steps. This allows the particles to achieve both monodispersity (from the controlled seed formation) and high crosslinking (in the final step), resolving the contradiction between particle uniformity and crosslinking level.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent segments the polymerization process into distinct stages: (1) formation of monodisperse seed particles, (2) swelling of seeds with monomer and crosslinker, and (3) crosslinking polymerization. This segmentation allows each stage to be optimized independently, enabling both high monodispersity and high crosslinking to be achieved.

Inventive Principle:
Principle #1Segmentation

2Productivity

If precipitation polymerisation is used to create larger particles of 0.5-10 micron, then particles can be formed in a short time span, but it is nearly impossible to produce porous particles with the same monomer composition and porosity for more than a very limited size variation

Engineering Contradiction:
Improveparticle formation speedVSAvoidporosity control
Core Design Contradiction:
ProductivityVSManufacturing precision

Solution Approach 1:

The patent uses preliminary action by pre-forming monodisperse seed particles with controlled size and composition, then using these as templates for subsequent growth. This ensures that all final particles inherit the same initial size distribution and porosity characteristics, maintaining both productivity and precision.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent applies parameter changes by controlling the swelling conditions (monomer concentration, crosslinker ratio, temperature) during the expansion phase. This allows precise control over final particle porosity while maintaining monodispersity, resolving the contradiction between formation speed and porosity control.

Inventive Principle:
Principle #35Parameter changes

3Manufacturing precision

If hydrophobic monomers are used in the Ugelstad process, then monodisperse particles can be produced, but the resulting particles are hydrophobic and suffer from non-specific absorption in biological applications

Engineering Contradiction:
Improveparticle size uniformityVSAvoidnon-specific absorption
Core Design Contradiction:
Manufacturing precisionVSObject-affected harmful factors

Solution Approach 1:

The patent applies parameter changes by selecting hydrophilic monomers (such as acrylic acid, acrylamide, or their derivatives) instead of hydrophobic monomers. This changes the chemical composition parameter of the particles, maintaining monodispersity while eliminating hydrophobicity and the associated non-specific absorption problem in biological applications.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent uses composite materials by incorporating hydrophilic monomers and crosslinkers that work together to create particles with both monodisperse structure and hydrophilic surface properties. This composite approach allows simultaneous achievement of manufacturing precision and reduced non-specific absorption.

Inventive Principle:
Principle #40Composite materials

4Stability of the object's composition

If a two-stage Ugelstad process is used to produce crosslinked porous monodisperse particles, then particles with controlled porosity can be obtained, but the smallest particles have an average diameter of at least 1 μm

Engineering Contradiction:
ImproveporosityVSAvoidparticle size
Core Design Contradiction:
Stability of the object's compositionVSLength of moving object

Solution Approach 1:

The patent uses preliminary action by forming very small monodisperse seed particles (smaller than 1 μm) through controlled emulsion polymerization, then using these as templates for subsequent swelling. This allows the final particles to maintain the small size of the seeds while acquiring the desired porosity through controlled monomer uptake, resolving the contradiction between porosity control and minimum particle size.

Inventive Principle:
Principle #10Preliminary action

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 method produces monodisperse polymer particles with low polydispersity and improved hydrophilicity, reducing non-specific absorption and enhancing their performance in biological assays.

Implementation Method 1

the seed particles are swollen by making a fine (e.g. submicron) aqueous emulsion of a relatively low molecular weight water-insoluble substance and then adding a water-miscible organic solvent (e.g. acetone) so that the water-insoluble substance diffuses into the seed particles

Methodology Applied
Scientific EffectSwelling:

Implementation Method 2

the water-insoluble substance diffuses into the seed particles

Methodology Applied
Scientific EffectDiffusion: Diffusion

Implementation Method 3

Following initiation of polymerization, e. g. by heating to activate the initiator, larger polymer particles are produced

Methodology Applied
Scientific EffectPolymerization: Photopolymerisation

Implementation Method 4

the seed particles take up a large quantity of monomer and also a crosslinker

Methodology Applied
Scientific EffectCrosslinking: Chemical Bonding

Implementation Method 5

made magnetic by the deposition of magnetic material in pores of the cross-linked monodispersed polymeric particles

Methodology Applied
Scientific EffectDeposition: Deposition (physical)

Implementation Method 6

provided with a coating, for example to modify the surface properties of the particles

Methodology Applied
Scientific EffectCoating: Coatings

Data Source

PatentEP3872101B1Polymeric particles
Publication Date: 2025.08.20 LIFE TECH AS
  • EP3872101B1 patent drawingFigure 1~2
  • EP3872101B1 patent drawingFigure 3~4
  • EP3872101B1 patent drawingFigure 5

AI summary

This invention relates to monodisperse coated hydrogel polymer particles comprising a polymer formed from (a) a hydrophilic vinylic monomer having a log Poct/wat (log P) of less than about 0.5; and (b) a crosslinker comprising at least two vinyl groups; and a coating. Also provided are methods of forming the monodisperse coated polymer particles.