Bis-Fluorescent Dye Linker for Short DNA Detection

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Solution Overview

Problem

Existing fluorescent dyes have insufficient sensitivity to detect short nucleic acids, such as ctDNA, in the DNA pre-staining method due to unstable binding when DNA length is shorter.

Innovation Solution

A compound with a linker that binds two fluorescent dye molecules to the nucleic acid at two sites, forming a stable complex for improved detection sensitivity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional fluorescent dyes are used to detect nucleic acids, then the detection method is simple, but the sensitivity is insufficient for short nucleic acids

Engineering Contradiction:

Improvedetection sensitivityVSAvoiddye structure complexity

Core Design Contradiction:

Measurement precisionVSDevice complexity

Solution Approach 1:

The patent combines two fluorescent dye molecules into a single compound through a linker, creating a bis-fluorescent-dye compound that binds to nucleic acids at two sites simultaneously. This merging of two dye molecules enhances the binding ability and detection sensitivity for short nucleic acids while maintaining a manageable structural complexity through the use of a flexible linker.

Inventive Principle:

Principle #5Merging (Combining)

2Stability of the object's composition

If a single fluorescent dye molecule binds to nucleic acid at one site, then the dye structure is simple, but the binding stability is insufficient for short DNA

Engineering Contradiction:

Improvebinding stabilityVSAvoiddye molecular structure

Core Design Contradiction:

Stability of the object's compositionVSDevice complexity

Solution Approach 1:

Two fluorescent dye molecules are merged through a linker to form a bis-fluorescent-dye compound that can bind to nucleic acids at two simultaneous sites. This dual-site binding mechanism significantly enhances binding stability for short DNA molecules compared to single-site binding, while the linker structure maintains flexibility and adaptability.

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The dye molecule is segmented into two independent fluorescent dye units connected by a linker, allowing each unit to bind to separate sites on the nucleic acid. This segmentation enables simultaneous dual-site binding, enhancing overall binding stability while keeping each individual dye unit structurally simple and well-defined.

Inventive Principle:

Principle #1Segmentation

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 compound enhances the binding ability of fluorescent dyes to nucleic acids, allowing for high-sensitivity detection of short DNA sequences.

Implementation Method 1

cyanine dyes are often used as fluorescent dyes... binding the derivative to nucleic acids... binding ability of fluorescent dyes to nucleic acids

Methodology Applied

Scientific EffectIntercalation:

Implementation Method 2

detecting the fluorescence intensity of a complex of the nucleic acid and the compound... enhances the binding ability of fluorescent dyes to nucleic acids

Methodology Applied

Scientific EffectFluorescence: Fluorescence

Data Source

PatentEP4674849A1Fluorescent dye for detecting nucleic acid

Publication Date: 2026.01.07 HITACHI HIGH TECH CORP

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Figure 3A~3J
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AI summary

Provided is a compound of the following formula (I): wherein R1, R2, R3, R4, R5, X, m, s, t, A, L, and Y- are as defined in the specification.