Flow-Through Ligand Coupling for Chromatographic Membranes

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Solution Overview

Problem

Chemical modification of membranes for ligand coupling is challenging due to the need for slow reaction kinetics, which limits the efficiency and scalability of affinity media modification processes.

Innovation Solution

A method involving a functionalized composite material with a macroporous cross-linked gel, arranged in a coplanar stack, tubular, or spiral wound configuration, where a ligand solution is flowed through or across to form covalent bonds with pendant reactive functional groups, enhancing ligand coupling and binding capacity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If roll-to-roll membrane modification process is used, then the membrane can be physically moved through reaction solution, but the reaction time becomes extremely long and processing efficiency decreases

Engineering Contradiction:
Improvemembrane modification processVSAvoidprocessing efficiency
Core Design Contradiction:
Ease of operationVSProductivity

Solution Approach 1:

Instead of moving the membrane through the reaction solution (roll-to-roll), the invention inverts the approach by flowing the reaction solution through the stationary membrane assembly. This allows the membrane to remain in place while reagents are delivered efficiently through the porous structure, dramatically reducing reaction time from hours to minutes while maintaining complete ligand coupling.

Inventive Principle:
Principle #13The other way round (Inversion)

Solution Approach 2:

The invention employs hydraulic flow of reaction solutions through the membrane assembly at controlled flow rates. This hydraulic delivery system ensures efficient reagent penetration into the porous membrane structure, enabling complete ligand coupling in minutes rather than the hours required by roll-to-roll methods.

Inventive Principle:
Principle #29Pneumatics and hydraulics

2Reliability

If slower movement of membrane through reaction solution is used, then ligand coupling can be complete, but processing time increases significantly

Engineering Contradiction:
Improveligand coupling completenessVSAvoidreaction time
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The hydraulic flow system delivers reagents directly through the membrane pores at optimized flow rates, ensuring complete ligand coupling occurs rapidly. The flow-through configuration maintains high reagent concentration at the reaction sites throughout the membrane, achieving complete coupling in minutes rather than hours.

Inventive Principle:
Principle #29Pneumatics and hydraulics

Solution Approach 2:

The membrane is pre-functionalized with reactive groups before ligand coupling, and the flow-through system is pre-configured with optimized reagent concentrations and flow rates. This preliminary preparation enables the actual ligand coupling reaction to proceed to completion very rapidly when the reagents are introduced.

Inventive Principle:
Principle #10Preliminary action

3Stability of the object's composition

If membrane is supported during modification, then membrane structure is protected, but diffusion of reagents into membrane is limited

Engineering Contradiction:
Improvemembrane structure integrityVSAvoidreagent diffusion
Core Design Contradiction:
Stability of the object's compositionVSEase of manufacture

Solution Approach 1:

The membrane assembly is segmented into multiple layers including porous support layers and active membrane layers with interconnected pore structures. This segmentation allows reagents to diffuse efficiently through the porous support structure while the membrane remains mechanically supported and protected throughout the modification process.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention utilizes porous support structures with controlled pore sizes and distributions that facilitate reagent diffusion while providing mechanical support to the membrane. The porous architecture allows reagents to penetrate deep into the membrane structure without compromising membrane integrity, enabling efficient ligand coupling throughout the entire membrane volume.

Inventive Principle:
Principle #31Porous materials

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

This method increases the dynamic binding capacity of affinity membranes, enabling rapid and productive chromatographic purification operations with improved ligand coupling efficiency compared to batch methods.

Implementation Method 1

a plurality of covalent bonds forms between the reactive functional groups and the first ligands

Methodology Applied
Scientific EffectCovalent bonding: Chemical Bonding

Data Source

PatentUS20220410076A1Methods for coupling a ligand to a composite material
Publication Date: 2022.12.29 MERCK MILLIPORE LTD
  • US20220410076A1 patent drawing
  • US20220410076A1 patent drawing
  • US20220410076A1 patent drawing

AI summary

Disclosed are methods for coupling a ligand to a composite material. Covalent bonds are formed between functionalized composite materials and ligands as a ligand solution flows through or across the composite materials. The composite materials are useful as chromatographic separation media.