Adsorptive Insoluble Surface for Chromatography Fouling Reduction
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Solution Overview
Problem
Current affinity chromatography surfaces face challenges with non-specific adsorption and fouling, which reduce the selectivity and binding capacity for target proteins, requiring harsh cleaning processes and increasing production costs in biopharmaceutical purification.
Innovation Solution
Development of an adsorptive insoluble surface with multiple ligand affinity domain regions connected by charged and non-charged joining regions, allowing for controlled binding and elution of target substances with reduced non-specific interactions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If affinity ligands are localized on insoluble surfaces for target binding, then selective affinity binding is improved, but non-specific adsorption and fouling increase
Solution Approach 1:
The patent introduces an intermediary substance (fouling reducer) that mediates between the affinity ligand and the target substance. This intermediary selectively binds to non-target entities such as host cell proteins and prevents their adsorption to the insoluble surface, while allowing the affinity ligand to maintain its selective binding to the target substance. The intermediary acts as a protective layer that reduces fouling without interfering with specific affinity interactions.
Solution Approach 2:
The patent modifies the surface properties of the insoluble support by changing parameters such as surface charge, hydrophobicity, or chemical composition through the application of fouling reducers. These parameter changes create a surface environment that is less prone to non-specific adsorption of proteins and other contaminants, while maintaining the affinity ligand's ability to selectively bind target substances.
2Productivity
If ligand density per support volume is increased for higher binding capacity, then productivity is improved, but non-specific adsorption increases
Solution Approach 1:
The fouling reducer serves as an intermediary that allows high ligand density to be maintained on the support surface without proportionally increasing non-specific adsorption. The intermediary selectively occupies sites that would otherwise bind non-target entities, enabling the system to achieve high productivity through increased ligand density while controlling fouling through the protective action of the intermediary substance.
3Duration of action of stationary object
If harsh chemical cleaning-in-place regimes are used to reduce fouling, then surface reusability is improved, but ligand stability and target affinity are reduced
Solution Approach 1:
The fouling reducer acts as a protective intermediary layer that prevents the accumulation of fouling materials on the affinity ligand and support surface. By reducing fouling during operation, the intermediary eliminates the need for harsh chemical cleaning cycles, thereby preserving ligand stability and target affinity while still enabling surface reusability through milder cleaning protocols.
Solution Approach 2:
The patent converts the potential harm of fouling into a benefit by using the fouling reducer to prevent fouling accumulation. This preventive approach transforms what would be a harmful condition requiring harsh cleaning into a manageable situation where mild cleaning is sufficient, thereby protecting the ligand from degradation while maintaining surface reusability.
4Measurement precision
If affinity constant is decreased to increase selectivity, then measurement precision is improved, but binding capacity is reduced
Solution Approach 1:
The fouling reducer intermediary allows the system to maintain a low affinity constant for high selectivity without sacrificing binding capacity. By preventing non-specific adsorption of contaminants and host cell proteins, the intermediary ensures that the binding capacity is utilized effectively for target substance binding, rather than being wasted on non-specific interactions.
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 approach enhances the binding capacity and reduces non-specific binding of host cell proteins, enabling milder elution conditions and improved surface reuse, thereby decreasing production costs and increasing the efficiency of biopharmaceutical purification processes.
Implementation Method 1
each ligand affinity domain region (ADR) has the ability of specific binding of at least one of the at least one substance
Implementation Method 2
at least the ligand ADR joining region (AJR) comprises at least one selected from the group consisting of at least one charged group (CAJR)
Implementation Method 3
whose functions depend on both controlled affinity adsorption and desorption of target substances
Data Source
AI summary
There is disclosed a relatively simple method to increase the performance of surface localised multi-valent affinity ligands whose target's isoelectric pH differs significantly from the ligand's optimal target-binding pH. This situation can result in ligand binding of target affecting local pH and subsequent binding of more target. Increasing the buffering capacity of the ligand via recombinant or other addition of charge groups to the ligand is expected to partially offset such effects, leading to enhanced binding capacity as well as possible secondary favourable alterations in regard to ligand elution pH, and non-specific surface binding of non-target proteins.