Polyallylamine Coated Membrane Sorber for High-Capacity Impurity Removal
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Solution Overview
Problem
Current membrane sorber technologies face limitations in binding strength and capacity for removing viruses, nucleic acids, and host cell proteins from biological solutions, particularly in monoclonal antibody purification, due to low surface area and inefficient surface modification methods.
Innovation Solution
A porous sorptive media with a polyallylamine or protonated polyallylamine coating is applied to the membrane surface, creating a loosely cross-linked hydrogel that significantly increases adsorptive capacity and binding strength, allowing for high-affinity removal of impurities without sacrificing device permeability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If conventional membrane sorbers with monolayer surface modification are used, then device permeability is maintained, but sorptive capacity is limited to approximately 20 mg/ml
Solution Approach 1:
The invention utilizes a porous polymeric coating layer with controlled porosity (50-80% pore volume) that allows penetrants to access binding sites within the coating matrix. This porous structure increases the effective surface area and binding capacity from 20 mg/ml to over 100 mg/ml while maintaining convective flow through the membrane, resolving the contradiction between capacity and permeability.
Solution Approach 2:
The invention creates a composite structure combining a porous membrane substrate with a polymeric coating layer containing binding groups. This composite approach allows the coating to provide high sorptive capacity while the porous substrate maintains permeability, achieving both high binding strength and device permeability simultaneously.
2Reliability
If polymeric primary amine coatings are applied to increase binding strength, then affinity for impurities improves, but manufacturing complexity increases
Solution Approach 1:
The invention optimizes coating parameters including polymer molecular weight (1,000-150,000), cross-linker concentration (0.01-2.0 wt%), and coating thickness (1-100 micrometers) to achieve high binding strength while maintaining manufacturability. The use of water-soluble polymers and simple cross-linking chemistry further simplifies the manufacturing process.
Solution Approach 2:
The invention uses water-soluble polymeric primary amines as intermediaries that can be easily applied to the membrane surface and then cross-linked to form a stable coating. This intermediary approach simplifies manufacturing compared to direct grafting methods, as the polymer solution can be uniformly applied and then stabilized through cross-linking.
3Measurement precision
If tight membrane pore size distribution is used to minimize axial dispersion, then separation efficiency improves, but mass transport rate decreases
Solution Approach 1:
The invention uses a porous polymeric coating with controlled pore size (0.01-10 micrometers) and porosity (50-80% pore volume) that allows rapid convective transport of penetrants while providing sufficient surface area for binding. The porous structure enables both high mass transport rates and efficient separation by allowing penetrants to access binding sites quickly.
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 enhances the sorptive capacity from 20 mg/ml to 80-100 mg/ml and maintains high flux, effectively removing impurities at high salt concentrations and conductivities, reducing the need for sample dilution and enabling efficient purification of monoclonal antibodies.
Implementation Method 1
Strong anion exchangers, such as those based on quarternary ammonium ions, are used in downstream processing as a polishing media for capturing negatively charged large impurities
Implementation Method 2
Adsorption refers to movement of molecules from a bulk phase onto the surface of an adsorptive media
Implementation Method 3
Absorption refers to taking up of matter by permeation into the body of an absorptive material
Implementation Method 4
membrane-based chromatographic systems (also called membrane sorbers), have the ligands attached directly to the convective membrane pores, thereby eliminating the effects of internal pore diffusion on mass transport
Implementation Method 5
the rate of mass transport is typically controlled by pore diffusion
Implementation Method 6
The coating is cross-linked to a sufficient degree to prevent dissolution of the coating polymer in water, yet the cross-linking is not so extensive as to compromise the flux through the membrane
Data Source
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AI summary
Media and devices, such as anion exchangers including such media, wherein the media is a membrane having a surface coated with a polymer such as a polyallylamine. The resulting membrane offers stronger binding of protein impurities and superior removal of host cell proteins from biological samples than conventional ligands based on quaternary ammonium salts, including trimethylammonium ligands. Also described is a chromatography scheme and method for purifying monoclonal antibodies, wherein the anion exchange sorber is placed downstream of an affinity column (such as Protein A or Protein G affinity column) and optionally one or more polishing devices such as cationic exchange columns. Little or no dilution of the cation exchanger pool (or affinity column exchange pool where no cation exchanger is used) is necessary to lower the conductivity of the sample. The sorber functions well to strongly bind host cell proteins and other impurities in biological samples even at high conductivities and pH.