Nucleic Acid Detection Dyes with PEG Solubility
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Solution Overview
Problem
Current nucleic acid detection methods using fluorescent dyes face challenges with aqueous solubility, stability, and fluorescence properties, particularly in advanced diagnostic platforms, and can inhibit isothermal nucleic acid amplification processes.
Innovation Solution
Development of dye compounds with improved properties, such as conformational and configurational stability upon intercalation into double-stranded DNA, characterized by a favorable signal-to-noise ratio and minimal inhibition of nucleic acid amplification, which emit a useful fluorescence signal upon irradiation, and are used in conjunction with polyethylene glycol moieties and anions for enhanced performance.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional fluorescent dyes are used for nucleic acid detection, then fluorescence signal can be obtained, but aqueous solubility and stability are insufficient
Solution Approach 1:
The patent employs composite material design by combining the fluorescent dye core structure with polyethylene glycol (PEG) side chains. This creates a hybrid molecule that integrates the fluorescence-generating capability of the dye with the solubility-enhancing properties of PEG, thereby simultaneously achieving both stability and aqueous solubility requirements
Solution Approach 2:
The patent modifies molecular parameters by introducing PEG moieties with varying chain lengths and configurations to the dye structure. This parameter change approach allows optimization of the balance between hydrophobic fluorescent core and hydrophilic PEG segments, enabling tunable solubility and stability characteristics
2Measurement precision
If fluorescent dyes are used for detection, then nucleic acid can be detected, but isothermal nucleic acid amplification processes are inhibited
Solution Approach 1:
The patent applies local quality modification by placing PEG groups specifically at certain positions on the dye molecule (R1-R5 positions in the general formula). This localized modification allows the dye to maintain its fluorescence detection capability while the PEG groups provide steric bulk and hydrophilicity that reduce non-specific binding and inhibition of amplification enzymes
Solution Approach 2:
The PEG moieties act as intermediary groups between the hydrophobic fluorescent core and the aqueous environment. This intermediary structure reduces direct interaction between the dye and amplification enzymes, thereby minimizing inhibition while maintaining detection function
3Ease of manufacture
If dyes with improved solubility are developed, then aqueous solubility increases, but conformational stability upon intercalation may be compromised
Solution Approach 1:
The patent segments the dye molecule into distinct functional domains: a rigid planar aromatic core for stable intercalation and fluorescence emission, and flexible PEG side chains for solubility. This segmentation allows each part to independently perform its function without compromising the other
Solution Approach 2:
The patent extends the molecule into additional spatial dimensions by attaching PEG chains that project outward from the planar intercalating core. This dimensional extension allows the core to maintain tight binding to DNA while the PEG chains extend into the solvent phase, providing solubility without interfering with the intercalation geometry
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
These dye compounds provide effective detection of nucleic acid analytes with sufficient endpoint intensity and minimal interference with amplification processes, offering improved sensitivity and specificity in nucleic acid detection.
Implementation Method 1
the compound of formula (I) in the presence of an energy (E1) and detecting emission of an energy (E2) from the sample
Implementation Method 2
the compound of formula (I) is conformationally and/or configurationally stable upon intercalation into double-stranded DNA
Data Source
AI summary
Provided herein are dye compounds having improved properties, such as aqueous solubility, stability, and fluorescence, as well as methods of detecting the presence or absence of an analyte in a test sample using said dye compounds.