Polymethine Fluorochrome Dyes for In Vivo Disease Imaging
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Solution Overview
Problem
There is a need for new fluorescent dyes that can be used in various medical and biological applications, particularly for optical imaging methods, which require dyes with high sensitivity and specificity for imaging diseases such as cancer, cardiovascular, and other diseases, where existing dyes may not meet the demands for purity and reproducibility.
Innovation Solution
The development of fluorochrome compounds with a polymethine bridge that absorb and emit light in the range of 500 nm to 1100 nm, which can be chemically linked to biomolecules for enhanced fluorescence and imaging applications, allowing for in vivo and in vitro imaging methods to detect and monitor diseases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If existing fluorescent dyes are used for optical imaging, then the imaging can be performed with current technology, but the sensitivity and specificity for detecting diseases such as cancer are insufficient
Solution Approach 1:
The patent modifies the molecular structure of fluorescent dyes by changing chemical parameters - specifically incorporating polymethine bridges with varying lengths and configurations, and adjusting the substitution patterns on the indole rings. These structural parameter changes result in dyes with enhanced fluorescence properties including higher quantum yield, red-shifted emission wavelengths, and improved photostability, which directly enhance disease detection sensitivity and imaging specificity
Solution Approach 2:
The invention creates composite fluorescent dye molecules by combining multiple functional units - indole chromophores, polymethine bridges, and various substituents (carboxyl, hydroxyl, amino groups) - into a single integrated molecular structure. This composite approach allows the dye to simultaneously achieve high fluorescence intensity, specific tissue penetration characteristics, and binding affinity for disease targets, thereby resolving the contradiction between sensitivity and specificity
2Stability of the object's composition
If polymethine dyes are used for labeling biological materials, then the dyes can form stable covalent bonds with biomolecules, but the degree of purity and reproducibility of synthetic methods are insufficient
Solution Approach 1:
The patent divides the polymethine dye molecule into distinct functional segments - the indole chromophore units, the polymethine bridge connecting them, and the substituent groups attached to the rings. This segmentation allows each component to be optimized independently for stability while the modular nature enables standardized synthesis procedures that can be reproduced reliably, as each segment can be introduced through well-defined chemical transformations
Solution Approach 2:
The invention systematically varies specific structural parameters such as the number of methine groups in the bridge, the position of double bonds, and the types of substituents attached to the indole rings. By controlling these parameters during synthesis, the patent achieves both stable covalent bonding (through optimized molecular structure) and reproducible manufacturing (through standardized synthetic protocols for each parameter variation)
3Measurement precision
If new fluorescent dyes are developed for medical applications, then imaging sensitivity can be improved, but the complexity of synthesis and purification increases
Solution Approach 1:
The patent employs preliminary action by using commercially available indole derivatives as starting materials and pre-assembling the polymethine bridge structures before final coupling to the biomolecule targets. This approach simplifies the overall synthesis by breaking down the complex dye molecule into manageable intermediates that can be prepared in advance, reducing the complexity of the final synthesis while maintaining high imaging sensitivity
Solution Approach 2:
The patent introduces intermediary compounds - specifically the polymethine bridge structures themselves - as mediators between the indole chromophore units and the final dye-biomolecule conjugate. These intermediaries serve as built-in linkers that facilitate the assembly process and can be easily purified, thereby reducing the overall synthesis complexity while enabling the creation of dyes with enhanced fluorescence properties for sensitive imaging
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 compounds provide enhanced fluorescence properties, enabling sensitive and specific imaging of biological targets, allowing for the detection and monitoring of diseases such as cancer and cardiovascular diseases, with improved sensitivity and specificity compared to existing dyes.
Implementation Method 1
exposing the subject to electromagnetic radiation, for example, light, of a wavelength absorbable by the fluorochrome compound
Implementation Method 2
detecting an optical signal emitted by the fluorochrome compound
Data Source
AI summary
The invention relates to a family of fluorescent compounds of Formula (I). The compounds can be chemically linked to biomolecules, such as proteins, nucleic acids, and therapeutic small molecules. The compounds can be used for imaging in a variety of medical, biological and diagnostic applications, and are particularly useful for the in vivo imaging of regions of interest within a mammal.