Affinity Chromatography Membrane Assembly with Inorganic Particles
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Solution Overview
Problem
Current affinity chromatography devices have limitations in achieving shorter residence times while maintaining or improving binding capacity, and they are not reusable without significant loss of dynamic binding capacity.
Innovation Solution
The development of an affinity chromatography device with a multilayered membrane assembly, comprising polymer membranes with inorganic particles of varying sizes and a thermoplastic impermeable layer, where the affinity ligand is covalently bound to the membranes, allowing for efficient separation of targeted proteins or antibodies at faster residence times and enabling multiple uses without substantial loss of binding capacity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional affinity chromatography devices are used to maintain binding capacity, then residence time is extended, but productivity decreases
Solution Approach 1:
The device segments the chromatography matrix into multiple discrete layers (e.g., 3-5 layers) with varying particle sizes and porosities. This segmentation allows optimization of each layer for specific functions: upper layers with smaller particles for high binding capacity, lower layers with larger particles for rapid flow-through, achieving both short residence time and maintained binding capacity
Solution Approach 2:
Different regions of the chromatography device are assigned different local qualities through the multilayer structure. Each layer has tailored particle size, porosity, and ligand density optimized for its position in the flow path, creating local conditions that collectively achieve both fast processing and high binding capacity
2Reliability
If conventional affinity chromatography devices are used to achieve high binding capacity, then device complexity increases, but ease of manufacture decreases
Solution Approach 1:
The device merges multiple chromatography layers into a single integrated cartridge assembly that functions as one manufacturable unit. The layers are pre-assembled with flow distributors and end caps in a unified manufacturing process, simplifying fabrication compared to assembling multiple separate components
Solution Approach 2:
The multilayer design serves multiple functions simultaneously: separation, purification, flow distribution, and structural support all within a single device architecture. The same layered structure that achieves high binding capacity also provides mechanical integrity and simplified manufacturing
3Productivity
If conventional affinity chromatography devices are used for repeated use, then dynamic binding capacity is maintained, but reusability is limited due to loss of binding capacity
Solution Approach 1:
The device incorporates preliminary protective measures through its multilayer structure that prevents damage during operation. The gradient of particle sizes and the presence of support layers prevent channeling, reduce mechanical stress on ligands, and minimize fouling before they can degrade binding capacity, enabling repeated use without significant loss of performance
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 device achieves a dynamic binding capacity of at least 30 mg/ml at 10% breakthrough at 20 seconds or less, with the ability to be reused multiple times after cleaning, significantly improving upon existing technologies in terms of efficiency and reusability.
Implementation Method 1
At least one polymer membrane and/or the inorganic particles has covalently bound thereto an affinity ligand that reversibly binds to a targeted protein or antibody
Data Source
AI summary
The present invention is directed to affinity chromatography devices that separate a targeted protein or antibody from an aqueous mixture containing the targeted protein or antibody. The chromatography device may contain a stacked membrane assembly or a wound membrane assembly. The membrane assemblies include (1) at least one polymer membrane that contains therein inorganic particles and (2) at least one impermeable layer (e.g., a thermoplastic polymer in a solid state). The polymer membrane and/or the inorganic particles have an affinity ligand bonded thereto. The affinity ligand may be a protein, an antibody, or a polysaccharide that reversibly binds to the targeted protein or antibody. The chromatography device may be repeatedly used and may be cleaned with a caustic solution between uses. The chromatography devices has a dynamic binding capacity (DBC) of at least 30 mg/ml (or 0.07 micromol/ml) at 10% breakthrough at a residence time of 20 seconds or less.