Silane Compounds for Immobilizing Biological Molecules on Solid Supports

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Solution Overview

Problem

Existing methods for immobilizing biological molecules on solid supports are limited by the reproducibility, sensitivity, and reusability of functionalized surfaces, often relying on dense monolayers of coupling agents that may not efficiently interact with a wide range of biological species.

Innovation Solution

Development of novel silane compounds with specific organic spacer groups and silyl groups that enable covalent or lower-energy interactions with biological molecules, allowing for reproducible and sensitive immobilization on various solid supports, including silicon and metal oxides, through the formation of organized monolayers and specific functional groups.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If dense monolayers of coupling agents are formed on solid supports, then the surface coverage is improved, but the sensitivity and reproducibility of biological molecule immobilization deteriorates

Engineering Contradiction:
Improvesurface coverageVSAvoidsensitivity
Core Design Contradiction:
Quantity of substanceVSMeasurement precision

Solution Approach 1:

The patent introduces an organic spacer group as an intermediary between the silyl group (attached to support) and the functional group (interacting with biological molecules). This spacer mediates the interaction by providing optimal spacing and orientation, allowing sensitive detection while maintaining surface coverage. The spacer acts as a molecular bridge that resolves the contradiction between coverage density and detection sensitivity.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention applies local quality by creating regions of high functional group density at specific locations (where biological molecules need to be immobilized) while using spacers to prevent excessive density that would reduce sensitivity. The organic spacer allows functional groups to be locally concentrated where needed while maintaining overall surface coverage, thus resolving the contradiction between quantity and precision.

Inventive Principle:
Principle #3Local quality

2Stability of the object's composition

If coupling agents are grafted to form organized monolayers, then the stability of the support is improved, but the reusability of the support deteriorates

Engineering Contradiction:
Improvesupport stabilityVSAvoidreusability
Core Design Contradiction:
Stability of the object's compositionVSAdaptability or versatility

Solution Approach 1:

The coupling agent is segmented into distinct functional modules: a silyl group for stable support attachment, an organic spacer for flexibility, and a functional group for biological molecule interaction. This segmentation allows the stable silyl-support bond to maintain support stability while the interchangeable functional groups enable reusability by allowing different biological molecules to be immobilized on the same support through repeated cycles.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention introduces dynamic characteristics through the organic spacer group, which provides flexibility and mobility to the functional groups. This dynamic structure allows the support to adapt to different biological molecules while maintaining stable attachment to the support, thus enabling reusability without compromising stability. The spacer allows the system to transition between different immobilization states.

Inventive Principle:
Principle #15Dynamics

3Strength

If silyl groups react with hydroxyl or hydride functional groups of supports, then the covalent bond strength is improved, but the complexity of the functionalization process increases

Engineering Contradiction:
Improvebond strengthVSAvoidfunctionalization process complexity
Core Design Contradiction:
StrengthVSDevice complexity

Solution Approach 1:

The invention utilizes parameter changes by selecting silyl groups with specific reactivity characteristics that match the hydroxyl or hydride functional groups on the support surface. By changing parameters such as the nature of the silyl group (e.g., trimethoxysilane, triethoxysilane) and reaction conditions, strong covalent bonds are formed through controlled hydrolysis and condensation reactions, achieving high bond strength while managing process complexity through systematic parameter optimization.

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 silane compounds facilitate efficient and specific immobilization of biological molecules, enhancing the sensitivity and reusability of solid supports for applications in chromatography, electrophoresis, and biosensors, while providing non-linear optical, electron conduction, and photoluminescence properties.

Implementation Method 1

X represents a silyl group capable of creating a covalent bond after reaction with the hydroxyl or hydride functional groups of a support

Methodology Applied
Scientific EffectCovalent bonding: Chemical Bonding

Implementation Method 2

arranged at the surface of the support generally in the form of a dense monolayer that is organized at the surface

Methodology Applied
Scientific EffectSelf-assembly: Self-Assembly

Implementation Method 3

the interaction possibly consisting of the formation of a covalent bond between the biological molecule and the coupling agent or of weaker bonds (such as electrostatic interactions, or dipolar bonds)

Methodology Applied
Scientific EffectElectrostatic interaction: Electrostatics

Implementation Method 4

organized at the surface, for example by formation of van der Waals type bonds between the grafted coupling agent molecules

Methodology Applied
Scientific EffectVan der Waals force: Van der Waals Force

Data Source

PatentUS9657042B2Silane compounds and use of same for functionalizing solid supports and immobilizing biological molecules on these supports
Publication Date: 2017.05.23 COMMISSARIAT A LENERGIE ATOMIQUE ET AUX ENERGIES ALTERNATIVES
  • US9657042B2 patent drawing
  • US9657042B2 patent drawing
  • US9657042B2 patent drawing

AI summary

The invention relates to novel silane compounds corresponding to the formula (I) below:A-E-X   (I)in which:X represents a silyl group capable of creating a covalent bond after reaction with the hydroxyl or hydride functional groups of a support;E represents an organic spacer group;A represents a group chosen from the groups of formulae below:in which:Z1 to Z5 independently represent a hydrogen atom or a halogen atom;Z6 and Z7 represent a group for protecting the phosphonic acid functional group, a hydrogen atom or a monovalent cation;Z8 to Z12 independently represent a group for protecting the carboxylic acid functional group, a hydrogen atom or a monovalent cation; andZ13 represents an imidazole, N-hydroxysuccinimide, nitrophenyl, pentafluorophenyl or acid anhydride group.Use of these silane compounds for functionalizing solid supports and for immobilizing biological molecules on these supports.