SPR Sensor Surface SAM PEG Segmentation

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Solution Overview

Problem

Current SPR sensor surfaces face challenges with high background noise and non-specific binding, leading to baseline drift and reduced assay performance, particularly due to matrix fluctuations and interactions with buffer components like detergents, necessitating the development of alternative matrices that minimize these issues.

Innovation Solution

A method involving the creation of a self-assembled monolayer (SAM) on a metal surface using thiol C10-C30 alkane reagents, where protein-resistant compounds like PEG are coupled to a fraction of the functional groups, and capturing molecules are directly immobilized on the SAM without being attached to the protein-resistant compounds, thereby minimizing non-specific binding and baseline drift.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If a hydrophilic matrix (e.g., carboxymethylated dextran) is used on the sensor surface, then ligand immobilization is enabled through carboxyl groups, but baseline drift and non-specific binding increase due to matrix fluctuations and interactions with buffer components

Engineering Contradiction:

Improveligand immobilization capabilityVSAvoidbaseline stability

Core Design Contradiction:

Adaptability or versatilityVSReliability

Solution Approach 1:

The sensor surface is segmented into distinct functional zones: a protein-resistant matrix (e.g., PEG) that provides baseline stability and non-specific binding resistance, and separate capturing molecules that are directly coupled to the surface without being attached to the matrix. This segmentation allows each component to perform its specific function independently, resolving the contradiction between ligand immobilization capability and baseline stability.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The capturing molecules are extracted from the traditional matrix-attached configuration and directly coupled to the sensor surface. This extraction eliminates the harmful matrix-fluctuation-induced baseline drift while preserving the ligand immobilization function, as the capturing molecules remain directly attached to the surface without being part of the fluctuating matrix structure.

Inventive Principle:

Principle #2Taking out (Extraction)

2Adaptability or versatility

If a traditional hydrophilic matrix is used, then capturing molecules can be immobilized, but assay noise increases due to matrix interactions with buffer components like detergents

Engineering Contradiction:

Improvecapturing molecule immobilizationVSAvoidassay noise from buffer interactions

Core Design Contradiction:

Adaptability or versatilityVSObject-affected harmful factors

Solution Approach 1:

The patent converts the traditionally harmful matrix- buffer interactions into a beneficial configuration by using a protein-resistant matrix (e.g., PEG) that specifically resists non-specific binding. This matrix choice transforms the potential harm of buffer component interactions into a benefit, as the matrix now provides resistance against unwanted interactions while allowing capturing molecules to be directly coupled for specific ligand binding.

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

3Adaptability or versatility

If capturing molecules are attached to the matrix, then ligand binding can be detected, but non-specific binding increases due to matrix properties

Engineering Contradiction:

Improveligand binding detectionVSAvoidnon-specific binding

Core Design Contradiction:

Adaptability or versatilityVSObject-generated harmful factors

Solution Approach 1:

The sensor surface is designed with local quality differentiation: the matrix region provides protein resistance and baseline stability, while the capturing molecule regions provide specific ligand binding capability. This local quality assignment ensures that non-specific binding is minimized in the matrix region while specific binding occurs at the capturing molecule sites, resolving the contradiction between ligand binding detection and non-specific binding.

Inventive Principle:

Principle #3Local quality

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 reduces assay noise and enhances sensor surface stability, allowing for more accurate kinetic and concentration assays by isolating capturing molecules from protein-resistant matrices, resulting in improved sensitivity and reduced non-specific binding.

Implementation Method 1

forming a self-assembled monolayer (SAM) on a surface by reacting said surface with one or more thiol C10-C30 alkane reagent(s)

Methodology Applied

Scientific EffectSelf-assembly: Self-Assembly

Implementation Method 2

one or more protein resistant compound(s) is/are coupled to a first fraction of the functional groups; and wherein one or more capturing molecule(s) is/are directly coupled to a second fraction of the functional groups

Methodology Applied

Scientific EffectChemical bonding: Chemical Bonding

Data Source

PatentUS11536657B2Sensor surface for surface plasmon resonance assays

Publication Date: 2022.12.27 CYTIVA SWEDEN AB

AI summary

The present invention relates to a method for production of an improved sensor surface for an SPR instrument, comprising forming a self assembled monolayer (SAM) on a surface and attaching ligands and protein resistant groups, preferably polyethylene glycol (PEG), directly to functional groups on said surface. The invention also relates to a sensor surface produced by these methods use thereof in SPR (surface plasmon resonance) assays or interactions.