Small Tunable Fluorophores for Deep-Tissue Biomolecule Imaging
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Solution Overview
Problem
Existing fluorescence imaging methods struggle to directly visualize small metabolites in live cells and intact organisms without impairing their native properties, as most fluorophores are bulky and incompatible with green fluorescent reporters, limiting their application for in vivo use.
Innovation Solution
Development of Small, Conjugatable, Orthogonal and Tunable Fluorophores (SCOTfluors) that emit in the NIR window (650-900 nm) and can be used to label small biomolecules, allowing direct imaging with minimal impact on their properties, and are compatible with other imaging modalities like Raman Scattering, optoacoustic imaging, and optical coherence tomography.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Length of stationary object
If bulky NIR fluorophores are used for deep tissue penetration, then imaging depth is improved, but the fluorophore impairs biomolecule trafficking and native properties
Solution Approach 1:
The patent applies parameter changes by systematically modifying the chemical structure of fluorophores to reduce their molecular weight and size. The SCOTfluors are designed with minimized molecular weight while maintaining NIR emission properties (650-900 nm), enabling deep tissue penetration without interfering with biomolecule function and trafficking
Solution Approach 2:
The patent applies local quality by designing fluorophores with specific local chemical properties that enable conjugation to biomolecules through functional groups (amines, alcohols, thiols, carboxylic acids) while maintaining small overall size. The fluorophore structure is optimized locally at the conjugation site to minimize steric interference with biomolecule behavior
2Ease of operation
If NBD fluorophores are used for small size and neutral character, then biomolecule native properties are retained, but compatibility with green fluorescent reporters is lost and in vivo application is limited
Solution Approach 1:
The patent applies universality by designing a platform of SCOTfluors that provides multi-color imaging capabilities across the visible and NIR spectrum (400-900 nm). The fluorophores maintain small size and neutral character for retaining biomolecule properties while enabling multi-color imaging through different emission wavelengths, and can be used in combination with GFP and other fluorescent reporters
Solution Approach 2:
The patent applies dynamics by creating a tunable series of fluorophores where emission wavelength can be dynamically adjusted across a broad spectrum. The SCOTfluors cover emission ranges from blue (400-500 nm) to NIR (650-900 nm), allowing flexible selection of appropriate fluorophores for different imaging applications and spectral requirements
3Measurement precision
If fluorescent labels are used to visualize metabolites, then direct imaging is enabled, but the labels impair how small biomolecules traffic within cells
Solution Approach 1:
The patent applies parameter changes by dramatically reducing the molecular weight parameter of fluorophores from conventional bulky structures (>500 Da) to small SCOTfluors (200-400 Da). This parameter change enables direct visualization of metabolites while minimizing the steric bulk that would otherwise interfere with biomolecule trafficking and cellular processes
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
SCOTfluors enable effective, multi-modal imaging of biomolecules in live cells and organisms, maintaining their native properties while providing deep penetration and low photodamage, suitable for cancer cell, immune cell, and stem cell imaging, as well as fluorescence-guided surgery.
Implementation Method 1
SCOTfluors include the smallest fluorophores emitting in the NIR window (650-900 nm) reported to date
Implementation Method 2
For optoacoustic imaging as they absorb NIR light
Implementation Method 3
they can be used as multimodal reagents as they can be readily detected under Surface-Enhanced Raman Scattering upon conjugation to metal surfaces
Data Source
AI summary
The invention relates to small, conjugatable, orthogonal and tunable fluorophores for imaging of small bioactive molecules. The invention further relates to processes for the preparation of the compounds, and uses of the compounds in therapeutic, diagnostic, surgery and analytical applications. The invention provides a compound of formula (I), a derivative or a salt thereof. Wherein X is selected from the group consisting of NH, O, S, SeR5R6, CR7R8; R1 is selected from the group consisting of amines, alcohols, thiols, thiophenols, selenols, selenophenols and aryl groups; R2 and R3 are independently H or a halogen; R4 tis either H, nitro or cyano; R5 is either absent or methyl or oxygen; R6 is either absent or methyl or oxygen; and R7 and R8 are independently selected from the group consisting of linear or cyclic alkyl groups containing halogen, amino, cyano or carboxylic ester substituents, and alkyl aryl groups.