Xanthene Dyes with Large Stokes Shifts for NIR Detection
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Solution Overview
Problem
Current clinical chemistry technologies require significant sample preparation and handling for analyzing complex biological samples, limiting diagnostic efficiency and increasing health hazards due to the lack of near-infrared (NIR) dyes that can function directly in biological media without separation steps.
Innovation Solution
Development of NIR dyes with enhanced Stokes shifts and bathochromic shifts, specifically xanthene-based regioisomeric naphthofluorone dyes that exhibit deep-red to NIR emission, allowing for direct detection of analytes in biological fluids like blood and urine with minimal sample manipulation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional NIR dyes are used, then minimal interfering absorption and fluorescence from biological samples is achieved, but the Stokes shift is very small (e.g., 10 nm), producing significant scattered light background signal and poor signal-to-noise ratio
Solution Approach 1:
The patent modifies the molecular structure of xanthene dyes by introducing specific substituents and extending conjugation systems, which changes the optical parameters (absorption and emission wavelengths) to achieve a large Stokes shift while maintaining NIR emission characteristics. This structural parameter change resolves the contradiction by enabling both small interfering absorption and large Stokes shift.
2Illumination intensity
If red-shifting xanthene dyes are used to extend emission wavelength, then the emission spectrum shifts toward longer wavelength, but the dyes suffer from limited water solubility and dimer formation
Solution Approach 1:
The patent introduces hydrophilic substituents (such as carboxylic acid groups, sulfonic acid groups, or hydroxyl groups) at specific positions on the xanthene dye molecule. This local modification enhances water solubility and prevents dimer formation while maintaining the extended conjugation system responsible for red-shifting the emission spectrum to NIR region.
3Measurement precision
If sample preparation and handling steps are performed for analyzing complex biological samples, then analysis accuracy is improved, but diagnostic time is increased and health hazards are increased
Solution Approach 1:
The NIR dyes are designed to function directly in biological media such as blood and urine without requiring external sample preparation or separation steps. The dyes self-interact with the analytes in the complex biological sample, enabling direct detection while maintaining accuracy. This eliminates the need for time-consuming and hazardous sample handling procedures.
4Illumination intensity
If established NIR dye classes (phthalocyanines, cyanine dyes, squaraine dyes) are used, then NIR emission is achieved, but the number of readily available classes is limited
Solution Approach 1:
The patent develops a universal xanthene-based dye platform that can be systematically modified through various substituents and conjugation extensions to achieve different NIR emission wavelengths and properties. This single versatile class of dyes replaces the need for multiple distinct dye classes, providing adaptability across different applications while maintaining NIR emission characteristics.
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 NIR dyes enable quicker and more accurate diagnostic testing by overcoming interference from biological samples, reducing health hazards, and providing stable, photostable solutions for detecting biomarkers in challenging media.
Implementation Method 1
Indicator fluorophores for specific biomarkers capable of functioning directly in an analyte's medium
Implementation Method 2
minimal interfering absorption and fluorescence from biological samples
Data Source
AI summary
Embodiments of near-infrared (NIR) dyes are disclosed, along with methods and kits for detecting analytes with the NIR dyes. The NIR dyes have a structure according to the general structureAt least one of R1/R2, R2/R3, R3/R4, R5/R6, R6/R7, and/or R7/R8 together forms a substituted or unsubstituted cycloalkyl or aryl.