NIR-Emitting Compounds With Long Lifetimes for In Vivo FLT
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Solution Overview
Problem
Current fluorescent probes used in fluorescence lifetime imaging (FLT) have short lifetimes in biological environments, making their detection complex, and there is a lack of compounds with near-infrared (NIR) emission and lifetimes greater than 1 ns, which are necessary for clinical applications.
Innovation Solution
Development of new NIR-emitting compounds with lifetimes greater than 1, 1.5, or 2 ns, featuring improved photophysical characteristics, photostability, and the ability to be modified for enhanced biocompatibility, encapsulation, and specific targeting, such as through conjugation with biological vectors or use in multimodal imaging agents.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional fluorescent probes are used in FLT imaging, then the imaging system can operate with existing technology, but the lifetime of the fluorophore is less than 1 nanosecond making detection complex
Solution Approach 1:
The patent applies parameter changes by modifying the fluorophore's emission wavelength to the near-infrared range (650-900 nm) and optimizing its lifetime to exceed 1 nanosecond in biological environments. This fundamental parameter change enables reliable detection with improved signal-to-noise ratio and discrimination from tissue autofluorescence, directly resolving the detection difficulty while maintaining reliability
Solution Approach 2:
The patent transitions from visible light fluorescence to near-infrared fluorescence, adding a new spectral dimension to the imaging system. This dimensional shift to longer wavelengths allows penetration deeper into tissues while achieving lifetimes greater than 1 ns, simultaneously improving detection reliability and reducing detection complexity
2Measurement precision
If fluorescent probes with long lifetime are developed, then detection sensitivity is improved, but the complexity of probe design and synthesis increases
Solution Approach 1:
The patent employs composite material design by combining specific molecular structures (such as BODIPY, cyanine, or porphyrin cores) with tailored substituents and linkers to achieve both long lifetime (>1 ns) and NIR emission. This composite approach allows systematic optimization of photophysical properties while managing synthesis complexity through modular design strategies
Solution Approach 2:
The patent applies segmentation by dividing the fluorophore into distinct functional modules: a core chromophore responsible for emission, linker regions for conjugation, and targeting moieties for specific binding. This modular segmentation enables independent optimization of each component's properties, achieving long lifetime and high sensitivity while simplifying the overall design process
3Length of stationary object
If NIR-emitting compounds are used, then tissue penetration depth is increased, but the lifetime in biological environment must be greater than 1 ns which limits available compounds
Solution Approach 1:
The patent systematically varies key parameters including emission wavelength (650-900 nm), lifetime (>1 ns), and molecular structure to identify compounds that simultaneously achieve deep tissue penetration and long lifetime in biological environments. This parameter optimization approach expands the available compound space beyond conventional fluorophores
Solution Approach 2:
The patent designs universal fluorophore platforms with core structures that can be adapted to multiple applications through modular conjugation with different targeting moieties. This multi-functionality approach allows a single optimized core structure to serve various imaging needs while maintaining the critical properties of NIR emission and long lifetime, effectively increasing compound availability
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 facilitate detection in vivo by providing improved sensitivity and specificity, overcoming limitations of tissue autofluorescence and light scattering, and enabling better contrast between targeted tumors and background noise.
Implementation Method 1
a fluorophore spends in the excited state before emitting a photon and returning to the ground state
Implementation Method 2
FLT uses time-correlated single photon counting (TCSPC) or other time-resolved techniques to capture the time delay between the excitation pulse and the emission of each photon
Implementation Method 3
fluorescence intensity is also strongly affected by the absorption/scattering of light by the tissues
Implementation Method 4
fluorescence intensity is also strongly affected by the absorption/scattering of light by the tissues
Data Source
AI summary
The present invention concerns compounds for use in in vivo fluorescence-lifetime imaging. The compounds have the following formula (1):