Diol-Bonded Organic Polymer Chromatography Column

Solution Overview

Problem

Columns packed with silica-based materials cannot withstand alkaline solutions, limiting their washing and sterilization capabilities, which is crucial for maintaining separation performance and removing adsorbed impurities in oligonucleotide separation and analysis.

Innovation Solution

A liquid chromatography method using a packing material formed by fixing a diol structure to crosslinked organic polymer particles, such as crosslinked polyvinyl alcohol, which allows for alkaline washing and sterilization, enhancing separation sensitivity and fractionation of oligonucleotides.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If a silica-based packing material is used for oligonucleotide separation, then separation performance is improved, but the column cannot withstand alkaline solutions for washing and sterilization

Engineering Contradiction:
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The invention uses a composite packing material consisting of a porous organic polymer base material combined with a diol bonding material. This composite structure provides both the separation performance needed for oligonucleotide analysis and the chemical stability required to withstand alkaline washing solutions, eliminating the limitation of silica-based materials that dissolve in base.

Inventive Principle:
Principle #40Composite materials

2Measurement precision

If silica-based columns are used, then high-sensitivity oligonucleotide separation is achieved, but column washing and sterilization with strong alkali is not possible

Engineering Contradiction:
Core Design Contradiction:
Measurement precisionVSEase of operation

Solution Approach 1:

The diol-bonded porous organic polymer composite provides a surface chemistry that enables both high-sensitivity oligonucleotide separation and robust alkaline washing capability, allowing routine column maintenance and sterilization that is not possible with silica-based columns.

Inventive Principle:
Principle #40Composite materials

3Productivity

If the column is continuously used without alkaline washing, then separation performance degrades due to adsorption of proteins and oligonucleotides, but switching to alkaline-washable columns is not possible with silica-based materials

Engineering Contradiction:
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The diol-bonded porous organic polymer composite material provides a chemically stable surface that resists adsorption of proteins and oligonucleotides, maintaining consistent separation performance over continuous use and enabling periodic alkaline washing to restore column performance without degradation.

Inventive Principle:
Principle #40Composite materials

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 method enables higher sensitivity in oligonucleotide separation and analysis, facilitates column washing and sterilization with alkaline solutions, and improves the fractionation of oligonucleotides, addressing the limitations of silica-based columns.

Implementation Method 1

A method based on hydrophilic interaction chromatography (HILIC) can be performed with an eluent containing a volatile salt at a low concentration

Methodology Applied
Scientific EffectHydrophilic interaction chromatography (HILIC): Absorption (physical)

Implementation Method 2

a packing material obtained by fixing a diol to a surface of each of porous particles formed of a crosslinked organic polymer or silica

Methodology Applied
Scientific EffectHydrophilic interaction: Absorption (physical)

Data Source

PatentEP3644055B1Separation/analysis method for mixture of oligonucleotides
Publication Date: 2022.04.13
  • EP3644055B1 patent drawingFigure 1
  • EP3644055B1 patent drawingFigure 2

AI summary

The present invention relates to a method of separating and analyzing a mixture of oligonucleotides, including performing liquid chromatography using a column packed with a packing material obtained by fixing a diol to a surface of each of porous particles formed of a crosslinked organic polymer. According to this method, the oligonucleotides can be separated and analyzed with higher sensitivity compared to cases where columns having silica gel as a base material are used. In addition, the column can be washed with an alkaline solution.