Affinity Chromatography Membrane Assembly for Rapid Protein Separation
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Solution Overview
Problem
Current affinity chromatography devices have limitations in terms of residence time and binding capacity, requiring longer processing times and not being reusable without significant loss of performance.
Innovation Solution
The development of an affinity chromatography device featuring a multilayered membrane assembly with polytetrafluoroethylene membranes and inorganic particles, where the membranes are wound or stacked and contain covalently bonded affinity ligands, allowing for efficient separation of proteins or antibodies at shorter residence times and maintaining binding capacity across multiple uses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Speed
If conventional affinity chromatography devices are used, then binding capacity is achieved, but residence time is excessively long
Solution Approach 1:
The patent transitions from traditional packed bed chromatography to a membrane-based system where the ligand is immobilized on a membrane surface. This dimensional change allows fluid to flow through the membrane, dramatically reducing residence time while maintaining binding capacity through the high surface area of the membrane structure.
Solution Approach 2:
The patent employs porous membrane materials that allow rapid fluid penetration while providing extensive surface area for ligand immobilization. The porous structure enables short residence times by allowing fluid to quickly pass through while the large surface area maintains high binding capacity for the target analyte.
2Reliability
If conventional affinity chromatography devices are used, then initial binding capacity is achieved, but reusability is poor
Solution Approach 1:
The patent designs a system where the membrane with immobilized ligand can be easily recovered and reused. The membrane structure allows for simple regeneration protocols where the membrane is retained in the device while flow-through conditions enable rapid washing and regeneration, maintaining binding capacity across multiple uses.
Solution Approach 2:
The membrane-based system enables self-regeneration through flow-through conditions where regeneration solutions can easily access the ligand surface. The structure allows the membrane to serve itself by enabling simple rinse and reuse cycles without complex disassembly or replacement procedures.
3Productivity
If shorter residence times are implemented, then productivity increases, but binding capacity decreases
Solution Approach 1:
By moving to a membrane surface-based system rather than packed particles, the invention creates a high surface area-to-volume ratio structure. This dimensional approach allows fluid to rapidly access binding sites (short residence time) while the extensive membrane surface provides numerous binding locations (high binding capacity).
Solution Approach 2:
The thin membrane film structure provides large surface area in a compact form factor, enabling rapid mass transfer and short residence times while maintaining high ligand loading capacity. The flexible membrane structure allows efficient fluid-membrane interaction for both rapid binding and quick elution.
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 in 20 seconds or less, with the ability to be reused multiple times without substantial loss of capacity, demonstrating improved efficiency and reusability.
Implementation Method 1
At least one of the polytetrafluoroethylene membrane and the inorganic particles has covalently bonded thereto an affinity ligand that reversibly binds to a targeted protein or antibody
Implementation Method 2
at least one polytetrafluoroethylene membrane containing therein inorganic particles having at least one nominal particle size
Data Source
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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.