Modified Fluorescent Dyes for Nucleic Acid Detection

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Current dyes used for protein and nucleic acid labeling lack optimal spectral characteristics and stability, leading to inefficiencies in detection and hybridization processes, particularly in applications requiring specific excitation and emission wavelengths.

Innovation Solution

Development of novel dyes with modified structures incorporating sulfonate, phosphate, and sulfone groups, which enhance solubility, stability, and binding affinity, allowing for improved spectral properties and reduced aggregation, and the use of these dyes in compositions with target molecules for enhanced detection and quantification.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional dyes are used for labeling, then the basic labeling function is achieved, but the spectral characteristics are not optimal and detection efficiency is reduced

Engineering Contradiction:
Improvedetection efficiencyVSAvoidspectral characteristics
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent modifies the chemical structure of conventional dyes by changing parameters such as adding sulfonate groups, phosphate groups, or sulfone groups to the dye molecules. These structural parameter changes result in improved spectral characteristics including enhanced fluorescence quantum yield, shifted emission wavelengths, and improved photostability, thereby resolving the contradiction between detection efficiency and spectral reliability

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates composite dye structures by combining conventional fluorescent dye cores with functional groups (sulfonate, phosphate, sulfone) and linker moieties. This composite approach allows the dye to simultaneously achieve optimal spectral properties for detection and stable binding to target molecules, addressing both detection efficiency and spectral reliability requirements

Inventive Principle:
Principle #40Composite materials

2Reliability

If dyes are modified to improve solubility and stability, then binding affinity and spectral properties improve, but the complexity of dye synthesis increases

Engineering Contradiction:
ImprovestabilityVSAvoidsynthesis complexity
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

The patent segments the dye molecule into distinct functional modules: a fluorescent core, soluble functional groups (sulfonate, phosphate, sulfone), and linker arms. This segmentation allows each module to be optimized independently and facilitates modular synthesis approaches, reducing overall synthesis complexity while improving stability and solubility

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent introduces linker arms as intermediary structures that connect the fluorescent dye core to the target molecule. These linkers serve as mediators that improve solubility and stability without directly affecting the core fluorescent properties, allowing for simplified synthesis by separating the functional requirements into distinct components

Inventive Principle:
Principle #24Intermediary (Mediator)

3Adaptability or versatility

If dyes are used for multiple labeling applications, then versatility is improved, but spectral overlap and interference increase

Engineering Contradiction:
Improvelabeling applicationsVSAvoidspectral overlap
Core Design Contradiction:
Adaptability or versatilityVSObject-affected harmful factors

Solution Approach 1:

The patent employs asymmetric cyanine dye structures with unequal aromatic ring systems to create dyes with unique spectral characteristics. This asymmetry in molecular structure results in distinct emission wavelengths that minimize spectral overlap when multiple dyes are used simultaneously for different labeling applications, thereby maintaining versatility while reducing spectral interference

Inventive Principle:
Principle #4Asymmetry

Solution Approach 2:

The patent modifies specific local regions of the dye molecule (such as adding electron-donating or electron-withdrawing groups at specific positions) to fine-tune the spectral properties. This local modification approach allows for precise control over emission wavelengths, enabling multiple dyes to coexist without significant spectral overlap while maintaining their respective labeling specificities

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

The modified dyes provide increased solubility, stability, and binding affinity, enabling more efficient detection and quantification of target molecules with improved spectral properties, addressing the limitations of existing dyes in labeling and hybridization processes.

Implementation Method 1

modified by the addition of charged groups as exemplified by sulfonates, phosphates, phosphonates and their derivatives. Other dyes have been modified by the addition of polar groups such as sulfoxide, sulfone and sulfonamide moieties

Methodology Applied
Scientific EffectSolubility enhancement through polar groups: Solvation

Implementation Method 2

The modified dyes provide increased solubility, stability, and binding affinity, enabling more efficient detection and quantification of target molecules

Methodology Applied
Scientific EffectMolecular binding: Adsorption

Implementation Method 3

The particular spectral characteristics of dyes are also important qualities. Although broad-spectrum white light can be used as a source of excitation, lasers with defined set wavelengths are most commonly employed

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Data Source

PatentUS8846952B2Detection or quantification of desirable target molecules, novel dyes, composite dyes, and oligonucleotides or polynucleotides comprising such dyes
Publication Date: 2014.09.30 ENZO LIFE SCIENCES INC
  • US8846952B2 patent drawing
  • US8846952B2 patent drawing
  • US8846952B2 patent drawing

AI summary

The present invention provides dyes, reactive dyes and labeled reagents that may be used in the detection or quantification of desirable target molecules, such as proteins and nucleic acids. Dyes are provided that may be used free in solution where the binding of the dye to the target molecule provides signal generation. Dyes are also provided that comprise reactive groups that may be used to attach the dyes to probes that will bind to desirable target molecules. The novel dyes of the present invention have been modified by the addition of charged and polar groups to provide beneficial properties.