Lipid-Modified Chromatography Surfaces for Selective Biomolecule Separation

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Existing polymeric solid phases in liquid chromatography face challenges in achieving highly selective separations due to non-uniform surface modifications, which can compromise the physical structure and result in heterogeneous distributions of active sites, limiting their effectiveness in separating biomacromolecules.

Innovation Solution

A surface-modified polymeric solid phase is introduced, featuring a hydrophobic surface with adsorbed lipids that have a hydrophobic end and a headgroup with binding functionality, allowing for targeted analyte separation through specific interactions without detrimental effects on the polymer backbone.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If active end group generation methods (aminolysis, hydrolysis, exposure to strong bases) are used to modify the polymeric solid phase surface, then a high density of functional groups is produced for analyte interaction, but the physical structure of the solid material is compromised and the polymer backbone breaks down

Engineering Contradiction:
Improvedensity of functional groupsVSAvoidintegrity of polymer backbone
Core Design Contradiction:
Quantity of substanceVSStability of the object's composition

Solution Approach 1:

The patent introduces a silane coupling agent as an intermediary substance that mediates between the polymeric solid phase and the desired functional groups. The silane first bonds to the polymer surface, creating a stable intermediate layer that prevents direct degradation of the polymer backbone, then subsequent functionalization occurs on the silane layer rather than directly on the polymer, thus protecting the polymer structure while still achieving high functional group density

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent applies preliminary surface treatment with silane coupling agents before introducing functional groups. This preliminary action creates a protective and reactive surface layer that enables subsequent functionalization without requiring harsh conditions that would degrade the polymer backbone, thus maintaining structural integrity while preparing the surface for high-density functional group attachment

Inventive Principle:
Principle #10Preliminary action

2Adaptability or versatility

If plasma grafting is used to generate tailored surfaces on polymeric fibers, then specific analyte interactions are enabled, but non-uniform oxidation occurs resulting in heterogeneous distributions of active sites

Engineering Contradiction:
Improvespecificity of analyte-surface interactionsVSAvoiduniformity of active site distribution
Core Design Contradiction:
Adaptability or versatilityVSManufacturing precision

Solution Approach 1:

The silane coupling agent serves as a uniform intermediary layer that distributes functional groups evenly across the fiber surface. Instead of direct plasma grafting that causes non-uniform oxidation, the silane layer provides a consistent platform for functional group attachment, ensuring homogeneous distribution of active sites while maintaining the ability to achieve specific analyte interactions

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the chemical parameters of surface modification by using silane-based chemistry instead of direct plasma grafting. This parameter change allows for controlled, uniform functionalization under milder conditions, transforming the modification process from a harsh, non-uniform plasma treatment to a controlled chemical grafting process that achieves both specificity and uniformity

Inventive Principle:
Principle #35Parameter changes

3Ease of manufacture

If conventional polymeric stationary phases are used in liquid chromatography, then chemical robustness and ease of derivatization are achieved, but highly selective separations are limited due to non-uniform surface modifications

Engineering Contradiction:
Improveease of chemical derivatizationVSAvoiduniformity of surface modification
Core Design Contradiction:
Ease of manufactureVSManufacturing precision

Solution Approach 1:

The silane coupling agent acts as a mediator that simplifies the derivatization process while improving uniformity. The silane layer provides a consistent, reactive surface that facilitates easy and uniform attachment of functional groups, combining the ease of derivatization with improved surface uniformity that enables highly selective separations

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The preliminary silane treatment creates a uniform, reactive surface platform that enables subsequent functionalization to proceed evenly across the entire stationary phase surface. This preliminary action ensures that ease of derivatization is maintained while the uniformity of the silane layer guarantees homogeneous functional group distribution for improved separation selectivity

Inventive Principle:
Principle #10Preliminary action

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 approach enables highly specific and stable surface modification of polymeric solid phases, enhancing separation efficiency and selectivity while maintaining the integrity of the polymer structure, allowing for effective separation of biomolecules with reduced non-specific binding.

Implementation Method 1

The lipid includes a hydrophobic end and a headgroup opposite the hydrophobic end, the hydrophobic end being adsorbed to the hydrophobic surface of the polymeric solid phase

Methodology Applied
Scientific EffectHydrophobic interaction: Hydrophobe

Implementation Method 2

The headgroup includes a binding functionality that can be used to target an analyte in a separation protocol

Methodology Applied
Scientific EffectAdsorption: Adsorption

Data Source

PatentUS9827552B2Functionalized lipid modification of solid phase surfaces for use in chromatography
Publication Date: 2017.11.28 CLEMSON UNIVERSITY
  • US9827552B2 patent drawing
  • US9827552B2 patent drawing
  • US9827552B2 patent drawing

AI summary

A solid phase for use in separation has been modified using an aqueous phase adsorption of a headgroup-modified lipid to generate analyte specific surfaces for use as a stationary phase in separations such as high performance liquid chromatography (HPLC) or solid phase extraction (SPE). The aliphatic moiety of the lipid adsorbs strongly to a hydrophobic solid surface, with the hydrophilic and active headgroups orienting themselves toward the more polar mobile phase, thus allowing for interactions with the desired solutes. The surface modification approach is generally applicable to a diversity of selective immobilization applications such as protein immobilization clinical diagnostics and preparative scale HPLC as demonstrated on capillary-channeled fibers, though the general methodology could be implemented on any hydrophobic solid support material.