Duplex Nucleic Acid Labels to Prevent Fluorescent Dye Self-Quenching

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Solution Overview

Problem

The incorporation of numerous individual dyes in markers leads to self-quenching, reducing fluorescence intensity and complicating quantitative analysis, especially in high-resolution studies.

Innovation Solution

A label comprising a nucleic acid backbone with a duplex structure and a plurality of labelling moieties, such as fluorescent dyes, is used to maintain rigidity and spacing, preventing dye aggregation and enhancing emission efficiency.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If numerous individual dyes are incorporated in markers, then sensitivity and detection capability are improved, but self-quenching occurs reducing fluorescence intensity

Engineering Contradiction:
Improvedetection sensitivityVSAvoidfluorescence intensity
Core Design Contradiction:
Measurement precisionVSIllumination intensity

Solution Approach 1:

A rigidifying agent is introduced as an intermediary substance that mediates between the dyes and the polymer backbone. This agent forms rigidifying structures that spatially separate the dyes while maintaining their attachment to the polymer, thereby preventing self-quenching and preserving fluorescence intensity even when multiple dyes are incorporated.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The physical state and spatial arrangement of dyes are changed by introducing rigidifying structures. This alters the distance and orientation parameters between adjacent dyes, preventing the close proximity that causes self-quenching while maintaining the high dye loading necessary for sensitive detection.

Inventive Principle:
Principle #35Parameter changes

2Measurement precision

If numerous individual dyes are incorporated in markers, then detection capability is improved, but quantitative analysis becomes complicated

Engineering Contradiction:
Improvedetection capabilityVSAvoidanalysis complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The rigidifying agent serves as a standardized intermediary that provides consistent spatial separation and rigidification. This standardization ensures uniform optical properties across different markers, simplifying quantitative analysis by reducing variability in fluorescence intensity that would otherwise complicate measurements.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

By controlling and standardizing the spatial arrangement parameters of dyes through rigidifying structures, the optical properties become predictable and consistent. This allows for simplified quantitative analysis as the relationship between dye concentration and fluorescence signal becomes more reliable.

Inventive Principle:
Principle #35Parameter changes

3Illumination intensity

If numerous individual dyes are incorporated in markers, then brightness is improved, but self-quenching reduces emission efficiency

Engineering Contradiction:
Improvelabel brightnessVSAvoidemission efficiency
Core Design Contradiction:
Illumination intensityVSLoss of energy

Solution Approach 1:

The rigidifying agent acts as a mediator that enables high dye loading for brightness while preventing the energy loss associated with self-quenching. By creating rigid structures that maintain optimal spacing, it allows multiple dyes to contribute to brightness without the harmful energy transfer between adjacent dyes.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The spatial parameters between dyes are optimized through rigidifying structures, maintaining distances that prevent self-quenching while allowing sufficient dye density for high brightness. This parameter control ensures that emission efficiency is preserved even as total fluorescence intensity increases through multiple dyes.

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 nucleic acid backbone with a duplex structure maintains the native optical properties of labelling moieties, providing bright and efficient emission, thereby improving sensitivity and accuracy in biological analysis.

Implementation Method 1

The nucleic acid backbone has a duplex structure comprising at least 50% of nucleotides of the nucleic acid backbone

Methodology Applied
Scientific EffectHydrogen bonding:

Implementation Method 2

The nucleic acid backbone is configured to allow formation of a duplex structure

Methodology Applied
Scientific EffectBase pairing:

Implementation Method 3

Self-quenching occurs when the proximity of dyes within a marker leads to non-radiative energy transfer among them, significantly diminishing the emission efficiency and the fluorescence intensity

Methodology Applied
Scientific EffectSelf-quenching prevention:

Data Source

PatentEP4653542A1Label, marker and method for analysing a biological sample
Publication Date: 2025.11.26 LEICA MICROSYSTEMS CMS GMBH
  • EP4653542A1 patent drawingFigure 1
  • EP4653542A1 patent drawingFigure 2
  • EP4653542A1 patent drawingFigure 3A

AI summary

A label (100, 200, 500, 702, 802, 900, 901, 1000, 1200, 1300, 1600) for analysing a biological sample is provided. The label (100, 200, 500, 702, 802, 900, 901, 1000, 1200, 1300, 1600) comprises a nucleic acid backbone (102, 502, 1002, 1102, 1202, 1301) and a first plurality of labelling moieties (104). The nucleic acid backbone (102, 502, 1002, 1102, 1202, 1301) has a duplex structure comprising at least 50% of nucleotides of the nucleic acid backbone (102, 502, 1002, 1102, 1202, 1301). In further aspects a marker (700, 800) comprising the label and a method for analysing biological samples is provided.