Mixed-mode chromatography membranes with multi-functional gel

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Solution Overview

Problem

Current methods for protein purification, such as affinity chromatography, are costly, require complex elution processes, and can lead to product aggregation, while traditional protein A chromatography has high immunogenicity and operational challenges.

Innovation Solution

Development of a composite material with a cross-linked gel having multiple functionalities, such as cationic, anionic, hydrophobic, and hydrophilic interactions, integrated into a membrane-based stationary phase for mixed-mode chromatography, allowing for enhanced selectivity, high flow velocity, and reduced back pressure.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If affinity chromatography is used for protein purification, then selectivity is improved, but cost increases significantly

Engineering Contradiction:

ImproveselectivityVSAvoidcost

Core Design Contradiction:

Manufacturing precisionVSEase of manufacture

Solution Approach 1:

The patent employs composite chromatographic media combining multiple functional groups (ion-exchange, hydrophobic, hydrophilic) within a single stationary phase. This composite approach achieves high selectivity for monoclonal antibodies through synergistic interactions while using abundant, cost-effective materials rather than expensive affinity ligands, directly resolving the contradiction between selectivity and manufacturing cost

Inventive Principle:

Principle #40Composite materials

Solution Approach 2:

The chromatographic media is designed with multi-functionality, incorporating cationic, anionic, hydrophobic, and hydrophilic functionalities in a single stationary phase. This universal design allows the same medium to provide multiple separation mechanisms simultaneously, achieving affinity-like selectivity without the high cost of specialized affinity ligands, thus resolving the cost-selectivity tradeoff

Inventive Principle:

Principle #6Universality (Multi-functionality)

2Manufacturing precision

If traditional protein A chromatography is used, then high selectivity is achieved, but operational complexity and immunogenicity risks increase

Engineering Contradiction:

ImproveselectivityVSAvoidoperational complexity

Core Design Contradiction:

Manufacturing precisionVSDevice complexity

Solution Approach 1:

The patent uses composite chromatographic media with multiple functional groups that work synergistically to achieve high selectivity for monoclonal antibodies. This composite approach eliminates the need for complex multi-step processes and specialized affinity ligands, simplifying operational procedures while maintaining high selectivity, thus resolving the contradiction between selectivity and operational complexity

Inventive Principle:

Principle #40Composite materials

Solution Approach 2:

The invention employs cost-effective, non-affinity-based chromatographic media that can be used without the stringent operational constraints of protein A. The media allows flexible elution conditions and does not require special handling procedures, reducing operational complexity while achieving comparable or superior selectivity

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

3Manufacturing precision

If conventional chromatography methods are used, then separation is achieved, but productivity is limited due to low flow velocity and high back pressure

Engineering Contradiction:

Improveseparation efficiencyVSAvoidflow velocity

Core Design Contradiction:

Manufacturing precisionVSProductivity

Solution Approach 1:

The patent employs porous chromatographic media with optimized pore structures that facilitate high flow rates while maintaining effective separation. The porous architecture provides large surface area for interactions without creating excessive back pressure, enabling high flow velocity and improved productivity while preserving separation efficiency, thus resolving the contradiction between separation quality and productivity

Inventive Principle:

Principle #31Porous materials

4Quantity of substance

If affinity chromatography with protein A is used, then high binding capacity is achieved, but product aggregation and precipitation occur during elution

Engineering Contradiction:

Improvebinding capacityVSAvoidproduct stability

Core Design Contradiction:

Quantity of substanceVSStability of the object's composition

Solution Approach 1:

The patent uses composite chromatographic media with multiple functional groups that provide gradual, controlled elution of bound proteins. The synergistic interactions prevent sudden conformational changes that cause aggregation, maintaining product stability during elution while preserving high binding capacity, thus resolving the contradiction between binding capacity and product stability

Inventive Principle:

Principle #40Composite materials

Solution Approach 2:

The invention allows elution under a wide range of pH and ionic strength conditions due to the multi-functional nature of the media. This flexibility enables selection of elution parameters that maintain product stability and prevent aggregation, while still achieving high binding capacity during the binding phase, resolving the contradiction between binding capacity and product stability

Inventive Principle:

Principle #35Parameter changes

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 composite material achieves high dynamic binding capacities, efficient protein purification with reduced aggregates, and operational flexibility, improving productivity and reducing costs compared to traditional methods.

Implementation Method 1

the first functionality and the second functionality are cationic, anionic, hydrophobic, hydrophilic, thiophilic, hydrogen bond donating, hydrogen bond accepting, pi-pi bond donating, pi-pi bond accepting, or metal chelating

Methodology Applied

Scientific EffectIon exchange: Ion Exchange

Implementation Method 2

Methodology Applied

Scientific EffectHydrophobic interaction: Hydrophobe

Implementation Method 3

Methodology Applied

Scientific EffectHydrogen bonding:

Implementation Method 4

Methodology Applied

Scientific EffectPi-pi interaction:

Implementation Method 5

contacting at a first flow rate a first fluid comprising a substance with any one of the aforementioned composite materials, thereby adsorbing or absorbing a portion of the substance onto the composite material

Methodology Applied

Scientific EffectAdsorption: Adsorption

Data Source

PatentUS11554361B2Mixed-mode chromatography membranes

Publication Date: 2023.01.17 MERCK MILLIPORE LTD

AI summary

Described are composite materials and methods of using them for mixed-mode chromatography. In certain embodiments, the composite material comprises a support member, comprising a plurality of pores extending through the support member; and a multi-functional cross-linked gel. The multi-functional cross-linked gel possesses at least two of the following functions or characteristics: cationic, anionic, hydrophobic, hydrophilic, thiophilic, hydrogen bond donating, hydrogen bond accepting, pi-pi bond donating, pi-pi bond accepting, or metal chelating. The composite materials may be used in the separation or purification of a biological molecule or biological ion.