Functionalized Fluorescent Markers for Steric Hindrance

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Solution Overview

Problem

Existing fluorescent markers for biological applications face challenges such as steric hindrance, altered spectral properties, limited solubility, and difficulty in synthesis, which hinder their effectiveness in multi-marking techniques and the detection of target molecules.

Innovation Solution

Development of new markers with functionalized dyes that maintain their spectral and solubility characteristics through the attachment of reactive groups to carbon atoms in the dye's chemical structure, allowing for easy functionalization and broad applicability across various dyes, including phthaleins, carbocyanins, merocyanins, porphyrins, and phthalocyanines.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If the reactive chemical function is linked directly to a carbon atom of the dye's hydrocarbon skeleton, then the marker can be synthesized, but steric hindrance greatly hinders coupling to target molecules and affects the absorption and fluorescence spectra

Engineering Contradiction:
Improvesynthesis capabilityVSAvoidcoupling ability
Core Design Contradiction:
Ease of manufactureVSEase of operation

Solution Approach 1:

The invention divides the marker structure into distinct segments: the dye core and the reactive chemical function, connected by a flexible linker chain. This segmentation allows the reactive function to be positioned away from the dye skeleton, reducing steric hindrance while maintaining synthesis feasibility.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

A flexible linker chain acts as an intermediary between the dye's hydrocarbon skeleton and the reactive chemical function. This intermediary component resolves the conflict by providing physical separation that reduces steric hindrance while still allowing the reactive function to perform its coupling role effectively.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Device complexity

If the reactive chemical function is located in the immediate vicinity of the dye cycle, then the marker structure is compact, but the absorption and fluorescence spectra are significantly affected

Engineering Contradiction:
Improvemolecular structure compactnessVSAvoidspectral properties
Core Design Contradiction:
Device complexityVSManufacturing precision

Solution Approach 1:

The marker is segmented into the dye core and reactive function separated by a linker, preventing the reactive function from interfering with the dye's spectral properties while maintaining a defined molecular structure.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The flexible linker chain serves as an intermediary that physically isolates the reactive chemical function from the dye cycle, thereby protecting the absorption and fluorescence spectra from significant alteration while still enabling coupling functionality.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Ease of operation

If existing markers are used for multi-marking, then detection can be performed, but partial overlapping of emission spectra distorts the reading of results

Engineering Contradiction:
Improvedetection capabilityVSAvoidspectral reading accuracy
Core Design Contradiction:
Ease of operationVSMeasurement precision

Solution Approach 1:

The invention enables precise control over the spectral parameters of markers by using various dyes with distinct absorption and emission characteristics. This parameter control allows selection of markers with minimal spectral overlap, improving measurement precision in multi-marking applications.

Inventive Principle:
Principle #35Parameter changes

4Measurement precision

If a wide range of markers with completely controlled spectral characteristics is required, then spectral overlap can be minimized, but access to such markers is limited

Engineering Contradiction:
Improvespectral characteristics controlVSAvoidmarker availability
Core Design Contradiction:
Measurement precisionVSAdaptability or versatility

Solution Approach 1:

The invention creates a universal platform for marker synthesis that can be applied to various dye types including phthaleins, carbocyanins, merocyanins, porphyrins, and phthalocyanines. This universal approach expands the available range of markers with controlled spectral characteristics, enhancing both precision and versatility.

Inventive Principle:
Principle #6Universality (Multi-functionality)

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 new markers enable precise labeling and detection of target molecules with minimal spectral overlap, improved solubility, and ease of synthesis, expanding their utility in biological and medical imaging applications.

Implementation Method 1

dyes having the ability to be excited transiently by absorption of light radiation and then to return to their initial state by emitting radiation whose wavelength is higher than that of excitation radiation

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Implementation Method 2

FRET (Fluorescence Resonance Energy Transfer) which exploits the transfer of energy from the excited state of a donor fluorescent label to a second acceptor fluorescent label

Methodology Applied
Scientific EffectFluorescence Resonance Energy Transfer:

Data Source

PatentEP1981846B1Markers, method for manufacturing them and their applications
Publication Date: 2017.11.01 LAB SYNTH INNOVE
  • EP1981846B1 patent drawing
  • EP1981846B1 patent drawing
  • EP1981846B1 patent drawing

AI summary

The present invention relates to labels capable of forming a covalent or non-covalent bond with a target molecule, consisting of a dye to which there is bonded in a covalent manner by one or more carbons of its chemical structure: one or more [FUNC] group(s), and optionally one or more [SOL] group(s), said label having the general formula: [DYE] representing the dye; [FUNC] each independently representing an —X-A-Z group, in which: X is chosen from the group consisting of an oxygen atom, a sulphur atom, an NR1R2 group, R1 and R2 each being independently of each other a hydrogen atom or a linear or branched C1-C30, preferably C1-C18 and more preferentially C1-C5 alkyl group; A is chosen from the group consisting of an alkylene group or an alkylene-arylene group; Z is a reactive chemical function; [SOL] each independently representing an —X′-A′-Z′ group, in which: X′ is chosen from the group consisting of an oxygen atom, a sulphur atom, an NR1R2 group, R1 and R2 each being independently of each other a hydrogen atom or a linear or branched C1-C30, preferably C1-C18 and more preferentially C1-C5 alkyl group; A′ is chosen from the group consisting of an alkylene group or an alkylene-arylene group; Z′ is a polar or apolar group.