Crosslinked Cellulose Hydrate Membrane for Hydrophobic Interaction Chromatography
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Solution Overview
Problem
Conventional adsorbents for hydrophobic interaction chromatography, particularly particulate adsorbents, face challenges such as high costs for loading, edge effects, pressure drop vs. transport kinetics antagonism, and slow operation due to diffusion limitations, leading to long dwell times and potential irreversible damage to target molecules.
Innovation Solution
Development of crosslinked cellulose hydrate membranes with hydrophobic ligands immobilized on their surfaces, which are produced through a process involving saponification and crosslinking of cellulose ester membranes to create a matrix with increased binding capacity and stability, allowing for efficient adsorption without collapsing at high ionic strengths.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If particulate adsorbents are used for hydrophobic interaction chromatography, then binding capacity can be achieved, but operation speed is slow due to diffusion limitations and long dwell times
Solution Approach 1:
The patent uses thin film adsorption membranes instead of particulate adsorbents. The membrane format eliminates diffusion limitations into particle interiors, allowing rapid mass transfer while maintaining high binding capacity through optimized ligand density on the membrane surface.
Solution Approach 2:
The invention transitions from zero-dimensional particulate adsorbents to two-dimensional membrane structures. This dimensional change enables flow distribution across the entire membrane surface, dramatically reducing dwell time and increasing operational speed while preserving binding capacity through controlled ligand immobilization.
2Quantity of substance
If particulate adsorbents are used, then binding capacity can be achieved, but pressure drop and transport kinetics are in antagonism
Solution Approach 1:
The thin film membrane structure provides a uniform flow distribution across the entire active surface, eliminating the pressure drop issues associated with packed beds of particulate adsorbents. This allows high binding capacity to be achieved without the antagonistic pressure drop problem.
3Productivity
If conventional membranes are used for HIC, then filtration can be performed, but binding capacity is insufficient
Solution Approach 1:
The patent creates composite membranes by immobilizing hydrophobic ligands (such as phenyl, butyl, hexyl, or octyl groups) onto the membrane surface or within the membrane matrix. This composite structure combines the filtration capability of the membrane base material with the high binding capacity of hydrophobic interaction chromatography ligands.
Solution Approach 2:
The invention utilizes porous membrane structures that provide both filtration functionality and high surface area for ligand immobilization. The porous architecture allows small molecules and proteins to access binding sites throughout the membrane, significantly enhancing binding capacity while maintaining filtration performance.
4Productivity
If membranes are used for HIC, then operation speed is improved, but mechanical strength requirements are higher than for particulate adsorbents
Solution Approach 1:
The patent employs thin film adsorption membranes with controlled thickness and structural reinforcement to achieve the necessary mechanical strength. The membrane design balances thinness for rapid mass transfer with sufficient structural integrity to withstand operational pressures, enabling high-speed operation without sacrificing mechanical durability.
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 cellulose hydrate membranes exhibit significantly higher binding capacities and improved separation performance compared to traditional methods, with a three-dimensional structure retained even at high ionic strengths, enhancing the efficiency and effectiveness of hydrophobic interaction chromatography.
Implementation Method 1
brought into contact with at least one solution under conditions which lead to swelling of the cellulose ester matrix and at the same time, i.e. in situ, to hydrolysis (saponification) of the ester groups to hydroxyl groups
Implementation Method 2
the resulting cellulose hydrate matrix is crosslinked by reacting the hydroxyl groups with one or more at least bifunctional reagents
Implementation Method 3
functional groups are immobilized, i.e. hydrophobic ligands that are capable of interacting with those contained in fluids Enter into adsorbent interactions
Data Source
AI summary
The invention relates to a cross-linked cellulose hydrate membrane having a porous double structure consisting of micropores having a diameter of between >100nm to 20µm and ultrapores which have a diameter of <100nm and are not accessible to blue dextran having an average molecular weight Mw of 2,000,000. The part of the volume of the ultrapores to the entire pore volume accessible to water is higher than 15 %. Hydrophobic ligands, selected from C1-C20 alkyl and the derivatives thereof, C6-C25 aryl and the derivatives thereof, or C7-C25 arylalkyl and the derivatives thereof or -[(CH2)m-O-]n-R, m being 2 or 3, n being a whole number higher than 1, and R being -H or -C1-C5 alkyl, are bound to the membrane. The invention further relates to methods for producing the membrane, to a device comprising the membrane and used for hydrophobic interaction chromatography, and to the use of said membrane in hydrophobic interaction chromatography.