Acridine Fluorescent Dye Composition for Clearer Base Sequencing
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Solution Overview
Problem
Current next-generation sequencing technologies face increased sequencing error rates due to the partial overlap of emission wavelengths of fluorescent dyes used for base identification, leading to poor distinguishability between different bases.
Innovation Solution
Development of acridine-based fluorescent dyes with a tricyclic rigid planar structure, synthesized using substituted xanthenes, which exhibit a blue shift in emission wavelength to the cyan light region, improving distinguishability and sequencing accuracy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional fluorescent dyes with green and red emission wavelengths are used for base identification, then the sequencing process can be completed, but the emission wavelengths partially overlap leading to poor distinguishability and increased sequencing error rates
Solution Approach 1:
The patent changes the emission wavelength parameter of the fluorescent dyes by developing new acridine-based dye structures with cyan emission wavelengths (480-490 nm), which are spectrally distinct from conventional green and red dyes, thereby improving base distinguishability and reducing sequencing errors
Solution Approach 2:
The patent creates composite fluorescent dye molecules combining acridine parent nucleus with various substituent groups (carboxyl, hydroxyl, amino, etc.) to achieve optimized optical properties including cyan emission wavelengths and high quantum yields, resulting in superior sequencing performance
2Measurement precision
If acridine-based fluorescent dyes with cyan emission wavelengths are developed, then sequencing accuracy is improved, but the dye synthesis requires multiple reaction steps
Solution Approach 1:
The patent segments the dye synthesis into modular reaction steps: first forming the acridine core structure from xanthene precursors, then sequentially adding functional groups (carboxyl, hydroxyl, amino substituents), allowing systematic optimization of each component's contribution to the final optical properties
Solution Approach 2:
The patent performs preliminary structural planning by selecting xanthene derivatives with specific substituents as starting materials, which are pre-designed to undergo cyclization and form the desired acridine core structure with predetermined functional groups, reducing the need for additional synthesis steps
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 new dyes enhance sequencing accuracy by providing clearer differentiation between bases, reducing error rates and improving sequencing quality.
Implementation Method 1
Acridine (azaanthracene) is a macrocyclic conjugated system with a tricyclic rigid planar structure and strong fluorescence
Data Source
Figure 1~2A
Figure 2B~3
Figure 4~5
AI summary
The present invention relates to a dye compound and a use thereof as a fluorescent marker, and also relates to a method for preparing the compound, a nucleotide or oligonucleotide labeled by the compound, and a nucleic acid sequencing method.