Functionalized Chromatography Support Material for Protein Purification

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Solution Overview

Problem

Current cation and anionic exchange chromatographic materials are costly to produce and inefficient for high molecular weight biomolecules due to slow diffusion and high material costs, necessitating the development of cost-effective alternatives for use in chromatography columns or cartridges.

Innovation Solution

A method involving the reaction of support materials with 3-(mercaptopropyl)trimethoxysilane or epoxy silane and 1,2-ethanedithiol to form thiol groups, followed by polymerization using monomers like 2-acrylamido-2-methyl-1-propanesulfonic acid, acrylic acid, or quaternary ammonium salts, utilizing a bromate ion-containing salt and deionized water, to create functionalized support materials with covalently bonded polymer chains, reducing the need for organic solvents and minimizing material costs.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If traditional cation and anionic exchange chromatographic materials are used, then protein purification can be achieved, but production costs are high and diffusion of high molecular weight biomolecules to the media surface is slow

Engineering Contradiction:
Improveprotein purification efficiencyVSAvoiddiffusion time of biomolecules
Core Design Contradiction:
ProductivityVSLoss of time

Solution Approach 1:

The patent divides the media surface into multiple functional zones by grafting polymer chains at different positions on the support material surface. This segmentation creates multiple access points and pathways for biomolecules, reducing diffusion distance and time while maintaining purification capacity

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent transitions from a traditional two-dimensional surface coating to a three-dimensional structure by grafting polymer chains that extend outward from the support material surface. This dimensional change creates a porous network that allows biomolecules to access functional groups throughout the volume rather than requiring surface diffusion

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

2Reliability

If traditional chromatographic materials are used, then separation function is provided, but material costs are high

Engineering Contradiction:
Improveseparation functionVSAvoidproduction cost
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

The patent changes the chemical parameters of the support material by introducing polymer chains with specific functional groups (carboxyl, sulfonic acid, quaternary ammonium) at controlled densities and distributions. This allows optimization of separation performance while using cost-effective base materials and grafting chemistries

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates composite chromatographic materials by combining a support material matrix with grafted polymer chains containing ionic functional groups. This composite structure provides the separation function through the polymer chains while the support material provides structural integrity at lower cost

Inventive Principle:
Principle #40Composite materials

3Quantity of substance

If tentacle concept with grafted polymer chains is applied, then protein loading capacity increases, but manufacturing complexity increases

Engineering Contradiction:
Improveprotein loading capacityVSAvoidmanufacturing process complexity
Core Design Contradiction:
Quantity of substanceVSDevice complexity

Solution Approach 1:

The patent applies preliminary action by pre-functionalizing the support material surface with initiator groups before polymerization. This allows the polymer chains to grow uniformly from predetermined sites, ensuring consistent protein loading capacity while simplifying process control through a standardized sequence of operations

Inventive Principle:
Principle #10Preliminary action

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 approach results in cost-effective, high-performance chromatographic materials capable of efficiently binding and separating biological compounds, such as proteins, with tailored polymer chain lengths and charges, enhancing protein purification capabilities while reducing production costs.

Implementation Method 1

oxidation of surface thiol groups to generate surface radicals

Methodology Applied
Scientific EffectOxidation: Oxidation

Implementation Method 2

surface radicals polymerize monomers

Methodology Applied
Scientific EffectRadical polymerization:

Implementation Method 3

Cation exchange chromatographic materials typically contain media having surface attached anionic groups... Anion exchange chromatographic materials typically contain media having surface attached cationic groups

Methodology Applied
Scientific EffectIon exchange: Ion Exchange

Data Source

PatentEP3137209B1Functionalized support material and methods of making and using functionalized support material
Publication Date: 2022.10.05 WR GRACE & CO CONN
  • EP3137209B1 patent drawingFigure 1~3
  • EP3137209B1 patent drawingFigure 4~5
  • EP3137209B1 patent drawing

AI summary

Methods of making functionalized support material are disclosed. Functionalized support material suitable for use in chromatography columns or cartridges, such as in a high pressure liquid chromatography (HPLC) column or a fast protein liquid chromatography (FPLC) column, is also disclosed. Chromatography columns or cartridges containing the functionalized support material, and methods of using functionalized support material, such as a media (e.g., chromatographic material) in a chromatography column or cartridge, are also disclosed.