Ion Exchange Chromatography Filler with Dual Cationic Groups

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Solution Overview

Problem

Current ion exchange chromatography methods fail to adequately detect nucleic acid chains that differ in sequence of bases or those with single base substitutions, leading to inefficient separation and detection processes.

Innovation Solution

A filler for ion exchange chromatography comprising base fine particles with both strong cationic and weak cationic groups on their surface, where the strong cationic group is capable of dissociating across a wide pH range and the weak cationic group is pH-dependent, allowing for effective retention and separation of nucleic acid chains.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional ion exchange chromatography using a single type of cationic group is used, then the operation is simple, but the detection of nucleic acid chains with sequence differences or single base substitutions is insufficient

Engineering Contradiction:
Improvedetection capability of nucleic acid chain differencesVSAvoidfiller structure complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The filler surface is designed with non-uniform distribution of cationic groups, creating different local binding environments. This allows simultaneous detection of different nucleic acid chain types through distinct binding affinities at different surface locations.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The filler combines multiple types of cationic groups (strong and weak) on the same particle surface to create a composite material with enhanced detection capability. This composite structure enables differentiation of nucleic acid chains that single-type fillers cannot distinguish.

Inventive Principle:
Principle #40Composite materials

2Measurement precision

If SSCP method with radioactive labeling is used, then SNP detection accuracy is improved, but the process becomes complicated and cost increases

Engineering Contradiction:
ImproveSNP detection accuracyVSAvoidprocess complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The invention extracts and eliminates the need for radioactive labeling and electrophoresis steps by using a specialized filler that directly separates and detects nucleic acid chains based on their inherent binding affinities to different cationic groups.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The mechanical electrophoresis system is replaced by a chemical binding system using ion exchange chromatography with a specialized filler, simplifying the detection process while maintaining accuracy.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

3Measurement precision

If RFLP method with restriction enzyme is used, then polymorphism detection is achieved, but analysis time and cost increase

Engineering Contradiction:
Improvepolymorphism detection capabilityVSAvoidanalysis time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The invention removes the restriction enzyme digestion step and PCR amplification requirements by using a filler that can directly bind and separate nucleic acid chains based on their sequence differences.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The filler is pre-designed with specific cationic group distributions that anticipate and directly recognize sequence differences, eliminating the need for preliminary enzymatic digestion and amplification steps.

Inventive Principle:
Principle #10Preliminary action

4Measurement precision

If conventional ion exchange chromatography is used, then operation is simple, but analysis time for accurate detection is prolonged

Engineering Contradiction:
Improvenucleic acid chain differentiation accuracyVSAvoidanalysis speed
Core Design Contradiction:
Measurement precisionVSProductivity

Solution Approach 1:

The invention changes the chemical parameters of the filler by incorporating both strong and weak cationic groups with different dissociation characteristics, enabling faster separation and detection of nucleic acid chains while maintaining accuracy.

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 filler enables sufficient detection and separation of nucleic acid chains with sequence differences or single base substitutions, improving analysis efficiency and reducing analysis time and complexity.

Implementation Method 1

Ion exchange chromatography is a method for separating a target substance using electrostatic interaction between an ion exchange group on a filler and an ion of the target substance

Methodology Applied
Scientific EffectElectrostatic interaction: Electrostatics

Implementation Method 2

Ion exchange chromatography includes a type based on anion exchange and a type based on cation exchange

Methodology Applied
Scientific EffectIon exchange: Ion Exchange

Data Source

PatentEP2674753B1Method for separating and detecting a nucleic acid strand
Publication Date: 2020.05.13 SEKISUI MEDICAL CO LTD
  • EP2674753B1 patent drawingFigure 1~2
  • EP2674753B1 patent drawingFigure 3~4

AI summary

The present invention aims to provide a filler for ion exchange chromatography which can sufficiently detect nucleic acid chains that differ in sequence of bases or nucleic acid chains that differ by a single base substitution. The present invention also aims to provide a method for separating and detecting a nucleic acid chain using the filler for ion exchange chromatography. The present invention relates to filler for ion exchange chromatography, comprising base fine particles, each particle having a strong cationic group and a weak cationic group on the surface thereof.