Phosphorylcholine Surface Modifier for Biocompatible Chromatography

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Solution Overview

Problem

Existing methods for coating surfaces with phosphorylcholine groups are inefficient, leading to incomplete coverage, durability issues, and loss of the surface's fine structures, while introducing low molecular weight derivatives results in unreacted functional groups that reduce biocompatibility and cause protein adsorption.

Innovation Solution

A compound with a phosphorylcholine group is directly reacted with a functional group that bonds to the surface, allowing for easy and versatile introduction of the phosphorylcholine group onto objects, creating a surface modifier that can be used to manufacture modified powders, chromatography packings, and glass devices with improved biocompatibility and reduced protein adsorption.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If polymer coating is used to introduce phosphorylcholine groups, then biocompatibility is improved, but the coating peels off and durability deteriorates

Engineering Contradiction:
ImprovebiocompatibilityVSAvoiddurability
Core Design Contradiction:
ReliabilityVSDuration of action of stationary object

Solution Approach 1:

The invention segments the phosphorylcholine-containing polymer into smaller molecular weight units (phosphorylcholine-containing compounds with 1-10 repeating units). These segmented units are then grafted onto the carrier surface, preventing the peeling issue of large polymer coatings while maintaining the biocompatible phosphorylcholine groups on the surface.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention applies phosphorylcholine groups locally on the carrier surface through grafting, rather than coating the entire surface with a thick polymer layer. This localized application maintains biocompatibility where needed (at the surface) while avoiding the durability problems associated with thick polymer coatings.

Inventive Principle:
Principle #3Local quality

2Productivity

If low molecular weight phosphorylcholine derivatives are used, then coating efficiency is improved, but unreacted functional groups remain causing protein adsorption

Engineering Contradiction:
Improvecoating efficiencyVSAvoidprotein adsorption
Core Design Contradiction:
ProductivityVSObject-generated harmful factors

Solution Approach 1:

The invention extracts and removes the problematic unreacted functional groups from the surface modification process. By using phosphorylcholine-containing compounds where the phosphorylcholine group is already formed (rather than requiring further reaction), the harmful unreacted functional groups are eliminated while maintaining high coating efficiency.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The invention converts the potential harm of small molecular weight compounds (which might leave unreacted groups) into a benefit by using compounds where the phosphorylcholine group is already complete and stable. The small size enables efficient coating, while the complete chemical structure prevents harmful unreacted groups.

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

3Reliability

If polymer coating is applied to the surface, then biocompatibility is improved, but fine structures including pores are lost

Engineering Contradiction:
ImprovebiocompatibilityVSAvoidfine structures
Core Design Contradiction:
ReliabilityVSShape

Solution Approach 1:

The invention applies phosphorylcholine groups only at the surface level through grafting, preserving the underlying fine structures and pores of the carrier. The local application ensures biocompatibility at the interface while maintaining the structural integrity and porosity of the base material.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The invention uses a thin layer of phosphorylcholine-containing compounds grafted on the surface, rather than a thick polymer coating. This thin film approach maintains biocompatibility while allowing the fine structures and pores of the carrier to remain accessible and functional.

Inventive Principle:
Principle #30Flexible shells and thin films

4Measurement precision

If silica gel is used as carrier, then chromatography performance is improved, but protein adsorption onto surface occurs

Engineering Contradiction:
Improvechromatography performanceVSAvoidprotein adsorption
Core Design Contradiction:
Measurement precisionVSObject-generated harmful factors

Solution Approach 1:

The invention introduces phosphorylcholine-containing compounds as an intermediary layer on the silica gel surface. This intermediary layer mediates between the silica gel carrier and the sample proteins, preventing direct adsorption onto the silica while maintaining the chromatographic separation performance of the carrier.

Inventive Principle:
Principle #24Intermediary (Mediator)

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 quantitative introduction of phosphorylcholine groups, minimizing protein adsorption and maintaining the surface's fine structures, resulting in superior biocompatibility and separation capabilities in chromatography, with enhanced durability and reduced protein denaturation.

Implementation Method 1

A compound with a phosphorylcholine group is directly reacted with a functional group that bonds to the surface

Methodology Applied
Scientific EffectChemical bonding: Chemical Bonding

Implementation Method 2

gives biocompatibility, moisture retaining properties, and other various useful functions to objects... minimizing protein adsorption

Methodology Applied
Scientific EffectAdsorption suppression: Adsorption

Data Source

PatentUS7906670B2Phosphorylcholine group containing compound and surface modifying agent composed of such compound
Publication Date: 2011.03.15 SHISEIDO CO LTD
  • US7906670B2 patent drawing
  • US7906670B2 patent drawing
  • US7906670B2 patent drawing

AI summary

A phosphorylcholine group-containing chemical compound represented by the following formula (1).In this formula, m denotes 2-6 and n denotes 1-4.X1, X2, and X3, independent of each other, denote a methoxy group, ethoxy group, or halogen. Up to two of X1, X2, and X3 can be any of the following groups: a methyl group, ethyl group, propyl group, isopropyl group, butyl group, or isobutyl group.R is one of the structures in the following formulas (2)-(4) (the chemical compound of formula (1) in the structures of the following formulas (2)-(4) is expressed as A-R—B).In formulas (2)-(4), L is 1-6, P is 1-3.Also a surface modifier consisting of the aforementioned phosphorylcholine group-containing chemical compound, modified powder treated with said surface modifier, a chromatography packing consisting of a modified carrier treated with said surface modifier, a filter treated with said surface modifier, and a glass device treated with said surface modifier.