Crosslinked Polymer for Phosphate Ester Isolation

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Solution Overview

Problem

Current methods for detecting and isolating phosphate ester-containing compounds, such as sphingosine-1-phosphate (S1P), are limited by high concentration requirements and risk of false results due to cross-reactivity, and lack efficient techniques for isolating and characterizing less-abundant and highly charged lipids like phosphorylated long-chain base phosphates (LCB-Ps) from complex biological samples.

Innovation Solution

Development of polymers through radical co-polymerization of specific monomers that selectively bind phosphate esters, allowing for their isolation and detection from biological samples using a solid phase separation method, which includes a higher proportion of cross-linking monomers and specific solvent systems for enhanced binding and elution.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If antibody-based ELISA kits are used to detect S1P, then detection can be performed, but only high S1P concentrations can be analysed and there is a relatively high risk of false results because of the cross-reactivity of the antibodies with similar molecules

Engineering Contradiction:
Improvedetection accuracyVSAvoidconcentration requirement
Core Design Contradiction:
Measurement precisionVSQuantity of substance

Solution Approach 1:

The patent changes the chemical parameters of the detection system by using polymers with different functional groups (imidazolium, pyridinium, triazolium) that selectively bind phosphate esters through non-covalent interactions. This chemical parameter change enables detection at lower concentrations and reduces cross-reactivity compared to antibody-based methods.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent employs composite polymer materials formed by copolymerizing monomers containing positively charged heteroaryl rings with cross-linking agents. These composite materials provide both the selective binding capability for phosphate esters and the structural stability needed for robust detection, overcoming the limitations of single-component antibody systems.

Inventive Principle:
Principle #40Composite materials

2Quantity of substance

If traditional partitioning procedures are used for lipid extraction, then abundant components can be extracted, but variable recovery of the less-abundant and highly charged lipids including phosphorylated signaling lipids occurs

Engineering Contradiction:
Improverecovery efficiencyVSAvoidextraction selectivity
Core Design Contradiction:
Quantity of substanceVSMeasurement precision

Solution Approach 1:

The patent applies local quality by designing polymers with specific functional groups localized at the polymer chain that are tailored to interact with phosphate ester groups. This localized functional design enables selective binding of phosphorylated lipids while allowing abundant non-phosphorylated lipids to pass through, achieving both high recovery and high selectivity.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The polymer acts as an intermediary material between the lipid mixture and the detection system. It selectively captures phosphorylated lipids through specific interactions with phosphate esters, thereby mediating the separation and enrichment process that improves both recovery efficiency and extraction selectivity for less-abundant charged lipids.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Strength

If a higher proportion of cross-linking monomer is used in polymer preparation, then the polymer structure becomes more robust, but the binding capacity for phosphate esters may be reduced

Engineering Contradiction:
Improvepolymer structural stabilityVSAvoidbinding capacity
Core Design Contradiction:
StrengthVSQuantity of substance

Solution Approach 1:

The patent optimizes the cross-linking ratio parameter to achieve the right balance between structural stability and binding capacity. By carefully controlling the proportion of cross-linking monomer (e.g., EGDMA) relative to the functional monomer, the polymer achieves sufficient mechanical robustness while maintaining adequate phosphate ester binding sites for effective capture.

Inventive Principle:
Principle #35Parameter changes

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 polymer effectively captures and separates phosphate ester-containing compounds, improving detection sensitivity and reducing matrix interference, enabling the identification and quantification of previously undetectable LCB-P species with enhanced signal intensity and precision.

Implementation Method 1

polymers which selectively bind phosphate esters... A is a 5- or 6-membered positively charged heteroaryl ring containing a quaternary nitrogen atom... selectively bind phosphate ester-containing compounds

Methodology Applied
Scientific EffectElectrostatic interaction: Ion Repulsion/Attraction

Implementation Method 2

long chain organic phosphate esters, for example phospholipids, are captured on a solid phase comprising a polymer of the invention

Methodology Applied
Scientific EffectAdsorption: Adsorption

Data Source

PatentEP3105268B1Crosslinked polymers prepared from functional monomers and use thereof
Publication Date: 2021.06.09 NATIONAL UNIVERSITY OF SINGAPORE
  • EP3105268B1 patent drawingFigure 1a~4e
  • EP3105268B1 patent drawingFigure 2a~2n
  • EP3105268B1 patent drawingFigure 3

AI summary

The invention relates to a polymer obtainable by radical co-polymerisation of a first monomer of general formula (I) or (II) or a mixture thereof: wherein A, A', B, B' X, Y, Y' and n are as defined herein; with a second, cross-linking monomer and optionally with one or more further co-monomers; wherein the molar ratio of the first monomer to other monomers is less than or equal to 1:5. The polymers selectively bind to phosphate ester compounds and can be used as a solid phase in a method for isolating compounds comprising a phosphate ester group from a mixture comprising one or more phosphate monoesters and/or phosphate diesters and/or other compounds such as lipids.