Bis-boron fused heterocyclic dyes for sequencing
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Solution Overview
Problem
Current fluorescent dyes for nucleic acid sequencing face challenges in achieving strong fluorescence under blue light excitation, chemical stability, and spectral distinguishability, particularly in aqueous environments, limiting their effectiveness in multiplex detection and high-throughput sequencing applications.
Innovation Solution
Development of bis-boron fused heterocyclic dyes with tunable absorption and emission properties, enhanced chemical stability, and strong fluorescence under blue light excitation, allowing for efficient labeling of nucleic acids and improved sequencing accuracy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Illumination intensity
If conventional fluorescent dyes are used for nucleic acid sequencing, then detection can be performed, but fluorescence intensity is significantly lower in water-based biological buffers and at higher temperatures
Solution Approach 1:
The patent modifies the chemical structure of fluorescent dyes by incorporating boron-containing heterocyclic rings and specific substituents (fluoro, chloro, alkyl groups) to enhance fluorescence quantum yield and photostability. This structural parameter change allows the dyes to maintain strong fluorescence signals in water-based buffers at physiological temperatures, directly resolving the contradiction between fluorescence intensity and environmental stability.
2Productivity
If multiple spectrally distinguishable fluorescent labels are used for multiplex detection, then throughput increases, but it becomes difficult to find dye compounds with substantially resolved absorption and emission spectra
Solution Approach 1:
The patent introduces distinct spectral characteristics to different dye molecules within the same class by varying local structural features (different substituents on the boron-containing heterocyclic core). This allows each dye to have a unique absorption and emission profile, enabling clear spectral separation for multiplex detection while maintaining consistent fluorescence properties across the dye set.
Solution Approach 2:
The patent creates a series of composite fluorescent dye molecules, each comprising a common boron-containing heterocyclic core structure combined with different substituent groups. This composite approach allows systematic tuning of spectral properties while maintaining a unified chemical platform, facilitating the development of multiplex dye sets with resolved spectra for high-throughput sequencing.
3Illumination intensity
If high power light sources like lasers are used for excitation, then fluorescence signal strength increases, but the dye must have sufficient photo-stability to withstand such excitation
Solution Approach 1:
The patent enhances photostability by incorporating boron-containing heterocyclic rings with specific substituents that increase the dye's resistance to photobleaching and photochemical degradation. This structural modification allows the dyes to withstand high-power laser excitation without significant signal loss, resolving the contradiction between achieving strong fluorescence signals and maintaining photo-stability under intense illumination.
4Object-affected harmful factors
If fluorescent dyes are used for sequencing, then non-radioactive detection is achieved, but chemical compatibility with reagent chemistries such as DNA synthesis solvents, buffers, and enzymes must be ensured
Solution Approach 1:
The patent designs dyes with chemically stable boron-containing heterocyclic cores and inert substituent groups that are compatible with DNA synthesis solvents, buffers, and enzymatic reactions. This chemical structure optimization ensures the dyes do not interfere with reagent chemistries or enzyme activities, maintaining adaptability while providing safe non-radioactive detection alternatives.
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 bis-boron fused heterocyclic dyes provide robust fluorescence signals, improved chemical stability, and spectral tunability, enhancing the accuracy and throughput of nucleic acid sequencing by enabling effective multiplex detection and reducing sequencing errors.
Implementation Method 1
Fluorescent dyes containing bis-boron fused heterocycles and uses in sequencing
Data Source
AI summary
The present application relates to substituted dyes containing bis-boron fused heterocycles and their uses as fluorescent labels. These compounds may be used as fluorescent labels for nucleotides in nucleic acid sequencing applications.