Affinity Chromatography Carrier with Ring-Opened Epoxy Groups
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Solution Overview
Problem
Affinity chromatography carriers face challenges such as high pressure in columns due to low elastic modulus of agarose particles, inconsistent quality, low hydrophilicity of styrene-divinylbenzene copolymers leading to low ligand activity, and inadequate impurity removal by methacrylate-based polymer particles.
Innovation Solution
A solid support copolymer comprising specific structural units from epoxy group-containing and polyvinyl monomers, with ring-opened epoxy groups, coupled with a ligand, providing high dynamic binding capacity, improved impurity removal, and storage stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If agarose particles are used as solid support, then high hydrophilicity is achieved, but low elastic modulus causes high pressure in column during high rate flow
Solution Approach 1:
The patent uses composite materials by combining agarose particles with a porous coating layer containing carboxymethyl cellulose and crosslinking agents. This composite structure maintains the hydrophilicity of agarose while the crosslinked coating network provides mechanical strength and elastic modulus to reduce column pressure during high rate flow.
Solution Approach 2:
The patent changes the physical and chemical parameters of agarose particles through crosslinking modification. By introducing crosslinking agents and controlling crosslinking degree, the elastic modulus is enhanced while maintaining porosity and hydrophilicity, resolving the contradiction between softness and mechanical strength.
2Strength
If styrene-divinylbenzene copolymer particles are used as solid support, then high mechanical strength and alkali resistance are achieved, but low hydrophilicity causes low ligand activity
Solution Approach 1:
The patent creates a composite structure by coating styrene-divinylbenzene copolymer particles with a hydrophilic layer containing carboxymethyl cellulose. This composite approach maintains the mechanical strength and alkali resistance of the polymer core while the hydrophilic coating layer restores ligand activity by providing adequate hydrophilicity.
Solution Approach 2:
The patent applies local quality modification by creating a surface coating layer with different properties than the core particles. The inner polymer core retains mechanical strength while the outer hydrophilic coating layer provides the necessary hydrophilicity for ligand activity, resolving the contradiction through spatial differentiation of properties.
3Strength
If methacrylate-based vinyl monomer polymer particles are used as solid support, then high hydrophilicity and mechanical strength are achieved, but insufficient ability to remove impurities remains
Solution Approach 1:
The patent introduces carboxymethyl cellulose as an intermediary substance in the coating layer that enhances impurity removal ability. This intermediary material works together with the methacrylate polymer to provide both mechanical strength and improved impurity removal through its specific chemical properties and interaction with impurities.
Solution Approach 2:
The patent modifies the chemical composition parameters of the coating layer by incorporating carboxymethyl cellulose with specific carboxyl group content. This parameter change enhances the ability to remove impurities while maintaining the mechanical strength provided by the methacrylate polymer backbone.
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 affinity chromatography carrier reduces nonspecific adsorption of impurities, maintains ligand activity over time, and enhances storage stability, enabling efficient purification of proteins like immunoglobulins with reduced costs.
Implementation Method 1
a copolymer including (M-1) 40 parts by mass or more to 80 parts by mass or less of a structural unit derived from an epoxy group-containing monovinyl monomer with respect to 100 parts by mass of all structural units and (M-2) 15 to 60 parts by mass of a structural unit derived from a polyvinyl monomer, and ring-opened epoxy groups
Implementation Method 2
a ligand coupled to the solid support
Data Source
AI summary
Provided is an affinity chromatography carrier that suppresses nonspecific adsorption of impurities, suppresses a decrease in dynamic binding capacity due to long-term storage, and has high storage stability. The affinity chromatography carrier includes a solid support including a copolymer including (M-1) more than 20 parts by mass and 99.5 parts by mass or less of a structural unit derived from an epoxy group-containing monovinyl monomer with respect to and (M-2) 0.5 to 80 parts by mass of a structural unit derived from a polyvinyl monomer with respect to all structural units; ring-opened epoxy groups obtained by subjecting the epoxy groups to the ring-opening ; and a ligand coupled to the solid support, and is such that after a certain column vessel is packed with the affinity chromatography carrier and then purged with a 2 M NaCl-containing 20 mM sodium phosphate buffer with a pH of 7.5, allowing the column to stand at 40°C for 7 days increases pH in the column by at most 2.