Multimodal Adsorption Medium for Biomolecule Purification at High Salt
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Solution Overview
Problem
Conventional chromatography media face challenges in achieving high binding capacity and reproducibility, especially at high salt concentrations, due to complex production processes and non-homogeneous ligand distribution, which affects the purification of biomolecules.
Innovation Solution
A multimodal adsorption medium with polymeric carrier material and multimodal ligands covalently bonded via a specific structure, allowing for high ligand density and salt tolerance, using a novel modification protocol that ensures consistent production and binding capacity across different salt concentrations.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If conventional chromatography media are used, then production processes are simple, but binding capacity and reproducibility are low especially at high salt concentrations
Solution Approach 1:
The invention segments the ligand structure into distinct functional domains: a multimodal ligand comprising a first functional group for cation exchange, a second functional group for hydrophobic interaction, and a third functional group for anion exchange. This segmentation allows each functional group to contribute specifically to binding capacity under different salt conditions, resolving the contradiction between manufacturing simplicity and binding performance.
Solution Approach 2:
The invention uses composite materials by combining multiple functional groups (cation exchange, hydrophobic interaction, anion exchange) within a single multimodal ligand structure attached to the chromatography matrix. This composite approach enables the media to maintain high binding capacity across a wide salt concentration range, addressing the limitation of conventional single-function ligands.
2Quantity of substance
If ligand density is increased to improve binding capacity, then salt tolerance decreases due to non-homogeneous ligand distribution
Solution Approach 1:
The invention applies local quality by ensuring homogeneous distribution of multimodal ligands across the chromatography matrix surface. Each ligand position contains all three functional groups (cation exchange, hydrophobic interaction, anion exchange) in consistent ratios, which maintains reliable salt tolerance even at high ligand densities. This eliminates the non-homogeneous distribution problem of conventional media.
Solution Approach 2:
The invention changes the chemical parameters of the ligand structure by introducing multimodal functionality with specific functional groups that have different charge states and interaction mechanisms. This parameter change allows the ligands to maintain effective binding across varying salt concentrations, resolving the trade-off between ligand density and salt tolerance.
3Ease of manufacture
If conventional single-function ligands are used, then production is straightforward, but purification effectiveness at elevated salt concentrations is poor
Solution Approach 1:
The invention implements universality by designing multimodal ligands that perform multiple functions simultaneously: cation exchange via the first functional group, hydrophobic interaction via the second functional group, and anion exchange via the third functional group. This multi-functionality enables effective purification across a broad range of salt concentrations without complicating the production process, as the multimodal ligands are attached using standard chromatography media manufacturing techniques.
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 solution provides a reproducible and high-binding-capacity adsorption medium that effectively purifies biomolecules, including small proteins, even at elevated salt concentrations, with improved salt tolerance and consistent performance.
Implementation Method 1
multimodal ligands of the formula -G-(CO2H)n, wherein X denotes —NR—, —O— or —S— and R denotes alkyl, alkenyl, aryl, heteroaryl or hydrogen, G denotes a group selected from the group composed of a branched or unbranched C2-20 alkyl group that can contain one or a plurality of heteroatoms selected from O, S, N and halogens, and optionally at least one aromatic substituent, a substituted or unsubstituted C3-10 cycloalkyl group that can contain one or a plurality of heteroatoms selected from O, S, N and halogens, and optionally at least one aromatic substituent, a branched or unbranched C2-20 alkenyl group that can contain one or a plurality of heteroatoms selected from O, S, N and halogens, and optionally at least one aromatic substituent, a substituted or unsubstituted C6-20 aryl group that can contain one or a plurality of heteroatoms selected from O, S, N and halogens, and a substituted or unsubstituted C4-20 heteroaryl group that can contain one or a plurality of heteroatoms selected from O, S, N and halogens
Implementation Method 2
G denotes a group selected from the group composed of a branched or unbranched C2-20 alkyl group that can contain one or a plurality of heteroatoms selected from O, S, N and halogens, and optionally at least one aromatic substituent
Implementation Method 3
multimodal ligands of the formula -G-(CO2H)n wherein X denotes —NR—, —O— or —S— and R denotes alkyl, alkenyl, aryl, heteroaryl or hydrogen
Implementation Method 4
The binding of the adsorbates to the adsorbent can be reversible or irreversible, and in any case, it allows them to be separated from the fluids
Implementation Method 5
The present invention relates to a multimodal adsorption medium, in particular a multimodal chromatography medium
Data Source
AI summary
The present invention relates to a multimodal adsorption medium, in particular a multimodal chromatography medium, a method for its production, as well as use of the adsorption medium according to the invention or an adsorption medium produced according to the invention for the purification of biomolecules.