Multi-Modal Ion-Exchange Membranes for High-Conductivity Biologic Purification
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Solution Overview
Problem
Current chromatography systems for biologics purification face challenges with low mass throughput, long processing times, high product degradation, and high costs due to low capacity for removing biological impurities under conditions of high solution conductivity, which are exacerbated by the transition to small-batch production in biopharmaceutical facilities.
Innovation Solution
Development of multi-modal ion exchange membranes with grafted polymers and functional ligands that provide multiple modes of sorptive functionality, including ionic and hydrophobic interactions, enabling high binding capacity and fast processing speeds even at high solution conductivities.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional resin column chromatography is used, then reliable purification is achieved, but processing time is long and productivity is low
Solution Approach 1:
The patent replaces traditional thick resin columns with thin-film ion-exchange membranes, reducing the path length for mass transfer and enabling faster processing while maintaining purification effectiveness. The membrane structure provides reliable separation with significantly reduced residence time compared to conventional resin columns.
Solution Approach 2:
The patent employs porous ion-exchange membranes with optimized pore structures that enable rapid mass transfer of biologics and impurities. The porous architecture maintains high binding capacity while allowing fast flow rates, resolving the contradiction between reliable purification and processing speed.
2Reliability
If traditional resin column chromatography is used, then purification is effective, but product degradation is high due to long processing times
Solution Approach 1:
The thin-film membrane structure reduces residence time from hours to minutes, minimizing exposure of biologics to harsh conditions and reducing degradation while maintaining effective purification through the membrane's selective binding properties.
3Productivity
If membrane chromatography is used to increase processing speed, then productivity improves, but binding capacity for impurities decreases under high conductivity conditions
Solution Approach 1:
The patent employs composite ion-exchange membranes that combine multiple functional groups and materials to maintain high binding capacity for biological impurities under high conductivity conditions while preserving fast processing speeds. The composite structure addresses the limitation of conventional membranes that lose capacity at high conductivities.
Solution Approach 2:
The patent optimizes membrane parameters including charge density, pore size, and hydrophobicity to maintain binding capacity across a range of conductivity conditions. These parameter adjustments enable the membrane to function effectively at high conductivities where traditional membranes fail, while retaining fast processing capabilities.
4Quantity of substance
If large column operations are used, then purification capacity is sufficient, but footprint is large and flexibility is reduced
Solution Approach 1:
The thin-film membrane technology provides high purification capacity in a compact format, reducing the footprint significantly compared to large resin columns while maintaining sufficient capacity through the membrane's high surface area and efficient mass transfer properties.
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 multi-modal ion exchange membranes achieve double the protein dynamic binding capacity of commercial products at half the residence time, significantly reducing production costs and product loss by efficiently removing impurities such as host cell proteins, aggregates, and DNA, thereby enhancing the economic viability of biologics production.
Implementation Method 1
The functional groups can be charged positively (anion exchangers) or negatively (cation exchangers) and interact with charged molecules primarily via Coulombic interactions.
Implementation Method 2
The functional ligand can provide multiple modes of sorptive functionality to the membrane, and at least one of the modes can be ionic functionality. For instance, upon the functionalization of the polymer, each ligand can provide cationic functionality as well as a secondary sorptive functionality, e.g., hydrophobic functionality.
Data Source
AI summary
Ion exchange membranes (e.g., anion exchange membranes) and methods of using the membranes are described. The ion exchange membranes are multi-modal ion exchange membranes containing a plurality of multi-modal exchange ligands. The membranes can achieve high dynamic and equilibrium binding capacities at solution conductivities typical for production of biologics (e.g., greater than about 10 mS/cm) and can provide excellent binding at high flow rates. Systems incorporating the membranes can dramatically increase isolation and purification speeds. Membranes are disclosed for use in production of biologics.