Hypercrosslinked Magnetic Particles for Diagnostic Automation

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Solution Overview

Problem

Current methods for preparing magnetic particles with high saturation magnetization are hindered by harsh reaction conditions, leading to low magnetization and particle size limitations, which are not suitable for automation processes.

Innovation Solution

A method involving the formation of magnetic particles with a polymer matrix and hypercrosslinked polymer, where magnetic cores are embedded and hypercrosslinked via a Friedel-Crafts reaction at temperatures below 80°C, resulting in particles with enhanced magnetization and size suitable for automation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If harsh reaction conditions are used to prepare magnetic particles, then crosslinking efficiency is improved, but saturation magnetization decreases and particle size is limited

Engineering Contradiction:
Improvecrosslinking efficiencyVSAvoidsaturation magnetization
Core Design Contradiction:
Ease of manufactureVSReliability

Solution Approach 1:

The invention changes the temperature parameter from harsh conditions (>80°C) to mild conditions (≤80°C) during the Friedel-Crafts hypercrosslinking reaction. This parameter change maintains crosslinking efficiency while preserving saturation magnetization, as demonstrated by particles prepared at 25°C achieving 10 A m2/kg compared to conventional methods that require higher temperatures but achieve lower magnetization.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention creates a composite structure with a polymer matrix containing hypercrosslinked regions and embedded magnetic cores. This composite approach allows the polymer matrix to provide structural support and porosity while the embedded magnetic cores maintain high saturation magnetization, resolving the contradiction between crosslinking efficiency and magnetization preservation.

Inventive Principle:
Principle #40Composite materials

2Stability of the object's composition

If conventional Friedel-Crafts reaction conditions are used, then hypercrosslinking is achieved, but particle size remains limited and automation is difficult

Engineering Contradiction:
Improvehypercrosslinked polymer structureVSAvoidautomation suitability
Core Design Contradiction:
Stability of the object's compositionVSExtent of automation

Solution Approach 1:

The invention changes the temperature parameter to ≤80°C (preferably 25°C) for the Friedel-Crafts reaction, which enables better control over particle growth and size distribution. This parameter change allows particles to reach sizes >2 μm suitable for automation while maintaining the hypercrosslinked polymer structure stability.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention uses an organic solvent as an intermediary medium to facilitate the Friedel-Crafts hypercrosslinking reaction under mild conditions. The solvent enables the reaction to proceed at ≤80°C while controlling the reaction rate and particle growth, making the process suitable for automated manufacturing.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Area of stationary object

If high surface area is required for analyte enrichment, then porous matrix is needed, but density increases and magnetization decreases

Engineering Contradiction:
Improvespecific surface areaVSAvoidmagnetization
Core Design Contradiction:
Area of stationary objectVSReliability

Solution Approach 1:

The invention creates a porous polymer matrix through controlled hypercrosslinking that provides high specific surface area for analyte enrichment. The porous structure is formed by the hypercrosslinked polymer network which creates interconnected voids, achieving >1000 m2/g surface area while the low-density polymer material prevents the density increase that would otherwise reduce magnetization.

Inventive Principle:
Principle #31Porous materials

Solution Approach 2:

The invention combines the porous polymer matrix with embedded magnetic cores to create a composite particle. The polymer matrix provides the high surface area porosity for analyte enrichment, while the embedded magnetic cores provide the magnetization, allowing both functions to coexist without the density problem of solid inorganic matrices like silica.

Inventive Principle:
Principle #40Composite materials

4Productivity

If particle size is increased for robust automation, then magnetic separation speed improves, but carry-over risk increases

Engineering Contradiction:
Improvemagnetic separation speedVSAvoidcarry-over prevention
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The invention changes the particle size parameter to >2 μm (preferably 5-50 μm) which optimizes the balance between magnetic separation speed and carry-over prevention. The hypercrosslinked polymer structure provides mechanical robustness to these larger particles, preventing fragmentation and carry-over during automated handling while maintaining fast magnetic separation.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention produces spherical particles with smooth surfaces, which improves flow characteristics during magnetic separation and reduces particle aggregation. The spherical shape with size >2 μm enables fast magnetic separation while the uniform geometry and robust hypercrosslinked structure prevent particle breakage and carry-over in automated systems.

Inventive Principle:
Principle #14Spheroidality (Curvature)

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 magnetic particles with high saturation magnetization and larger particle sizes, addressing the limitations of existing technologies and enabling efficient automation in diagnostic systems.

Implementation Method 1

polymerizing the polymer precursor molecules according to (ii) in the presence of the at least one magnetic core (M), thereby forming a particle comprising the at least one magnetic core (M), preferably the at least two magnetic cores (M), embedded in a polymer matrix (P1)

Methodology Applied
Scientific EffectPolymerization: Photopolymerisation

Implementation Method 2

hypercrosslinking the polymer matrix (P1) of the polymer particle obtained in (iii) via a Friedel-Crafts reaction, wherein the reaction is carried out at a temperature equal to or less than 80° C.

Methodology Applied
Scientific EffectFriedel-Crafts reaction: Chemical Bonding

Data Source

PatentUS20230381743A1Method for preparing highly porous polymer particles for diagnostic applications
Publication Date: 2023.11.30 ROCHE DIAGNOSTICS OPERATIONS INC
  • US20230381743A1 patent drawing
  • US20230381743A1 patent drawing
  • US20230381743A1 patent drawing

AI summary

The present disclosure relates to a method of preparing a magnetic particle having a polymer matrix (P) and at least one magnetic core (M), preferably at least two magnetic cores (M), wherein the polymer matrix (P) comprises at least one hypercrosslinked polymer, wherein the method comprises (i) providing at least one magnetic core (M), preferably at least two magnetic cores (M), (ii) providing polymer precursor molecules, (iii) polymerizing the polymer precursor molecules according to (ii) in the presence of the at least one magnetic core (M), thereby forming a particle comprising the at least one magnetic core (M). Further, the present disclosure relates to particles obtained or obtainable by this method as well as to the use of these particles. In a further aspect, the disclosure relates to a method for determining at least one analyte in a fluid sample having the step of contacting of the magnetic particle with a fluid sample having or suspected of having the at least one analyte.