Thioether Mixed-Mode Anion-Exchanger High Salt Adsorption

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Solution Overview

Problem

Conventional anion-exchange methods face challenges in efficiently adsorbing and desorbing negatively charged substances, particularly proteins, at high ionic strengths, and require extensive desorption protocols, which can lead to loss of chromatographic properties and high costs.

Innovation Solution

The development of anion-exchangers with mixed mode ligands containing a thioether linkage near a positively charged nitrogen atom, allowing for enhanced binding and desorption capabilities at varying ionic strengths, including high salt concentrations, and resistance to alkaline or acidic conditions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If conventional anion-exchange methods are used to adsorb negatively charged substances at high ionic strengths, then adsorption capacity is limited, but using mixed mode ligands with thioether linkage increases breakthrough capacity significantly

Engineering Contradiction:
Improvebreakthrough capacityVSAvoidligand structure complexity
Core Design Contradiction:
Quantity of substanceVSDevice complexity

Solution Approach 1:

The patent applies composite materials by combining thioether linkage with positively charged nitrogen structures to create mixed mode anion-exchange ligands. This composite structure integrates both ion-exchange functionality (from charged nitrogen) and enhanced binding capability (from thioether), resulting in significantly increased breakthrough capacity compared to conventional single-mode ligands.

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

The patent implements local quality by positioning the thioether linkage at specific locations within the ligand structure - specifically within 1-7 atoms from the positively charged nitrogen. This localized arrangement optimizes the interaction with negatively charged substances while maintaining the overall ligand architecture, achieving enhanced performance without excessive complexity.

Inventive Principle:
Principle #3Local quality

2Reliability

If extensive desorption protocols are used to remove bound substances, then complete desorption is achieved, but chromatographic properties are lost and costs increase

Engineering Contradiction:
Improvedesorption completenessVSAvoidloss of chromatographic properties
Core Design Contradiction:
ReliabilityVSLoss of substance

Solution Approach 1:

The patent applies parameter changes by utilizing the unique properties of thioether-linked ligands that allow desorption to be achieved through controlled changes in ionic strength and pH. The mixed mode ligands maintain stable binding at high ionic strengths during adsorption, then permit efficient desorption when parameters are adjusted, avoiding the need for extreme conditions that would damage chromatographic properties.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The thioether linkage acts as an intermediary that mediates between the positively charged nitrogen and the negatively charged substance. This intermediary structure provides stable binding during adsorption but allows controlled release during desorption, enabling complete substance removal while preserving the ligand's chromatographic properties for reuse.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Ease of operation

If conventional ligands are used, then desorption requires extreme conditions, but mixed mode ligands allow desorption under milder conditions

Engineering Contradiction:
Improvedesorption condition mildnessVSAvoidligand synthesis difficulty
Core Design Contradiction:
Ease of operationVSEase of manufacture

Solution Approach 1:

The patent applies parameter changes by designing mixed mode ligands with thioether linkage that fundamentally alter the desorption behavior. These ligands enable desorption under milder ionic strength and pH conditions compared to conventional ligands, because the thioether provides stable binding that doesn't require extreme conditions for disruption, making the process easier to operate.

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

These anion-exchangers demonstrate increased breakthrough capacities, high recovery rates, and stability, enabling efficient purification and removal of negatively charged substances with reduced sample dilution and simplified desalting procedures, while maintaining chromatographic properties.

Implementation Method 1

the positively charged nitrogen under conditions permitting binding between the ligands and the substance

Methodology Applied
Scientific EffectElectrostatic attraction: Ion Repulsion/Attraction

Implementation Method 2

The second site typically gives electron donor-acceptor interaction and/or hydrophobic interactions

Methodology Applied
Scientific EffectElectron donor-acceptor interaction:

Implementation Method 3

contacting the liquid with an anion-exchanger that comprises a base matrix carrying a plurality of mixed mode anion-exchanging ligands

Methodology Applied
Scientific EffectAdsorption: Adsorption

Implementation Method 4

desorbing said substance from said anion-exchanger by the use of a liquid (liquid (II))

Methodology Applied
Scientific EffectDesorption: Desorption

Data Source

PatentUS7879244B1Method for anion-exchange adsorption and thioether anion-exchangers
Publication Date: 2011.02.01 CYTIVA BIOPROCESS R&D AB
  • US7879244B1 patent drawing
  • US7879244B1 patent drawing
  • US7879244B1 patent drawing

AI summary

A method for the removal of a substance, which has a negative charge and which is present in an aqueous liquid (I). The method comprises the steps of: (i) contacting the liquid with an anion-exchanger (1) that comprises mixed mode anion-exchanging ligands in which there is a positively charged nitrogen allowing binding of the substance to the anion-exchanger; and (ii) desorbing said substance from said anion-exchanger. The characteristic feature is that (A) the mixed mode ligands have a thioether linkage within a distance of 1-7 atoms from their positively charged atom, and (B) the anion-exchanger (1) (i) is capable of binding the substance of interest in an aqueous reference liquid (II) at an ionic strength corresponding to 0.25 M NaCl, and (ii) permits in the pH interval 2-12 a maximal breakthrough capacity for the substance which is ≧200% of the breakthrough capacity of the substance for Q-Sepharose Fast Flow (anion-exchanger 2).