NIR Dye Design for Deep Tissue Photoacoustic Imaging
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Solution Overview
Problem
There is a scarcity of xanthene-based near-infrared (NIR) probes that absorb light above 800 nm, which are essential for deep tissue imaging due to their low fluorescent quantum yields and arduous synthetic routes, limiting their accessibility and imaging depth.
Innovation Solution
Development of a novel NIR dye comprising a counterion and a specific structure that absorbs light in the NIR I and II regions, utilizing a donor-acceptor-donor design with thiophene and xanthene groups to enhance charge transfer and absorption, resulting in a highly photostable and detectable photoacoustic signal.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Length of stationary object
If xanthene-based probes are designed to absorb light above 800 nm for deep tissue imaging, then imaging depth is improved, but fluorescent quantum yield decreases and synthetic complexity increases
Solution Approach 1:
The xanthene-based probe is divided into modular components: a core xanthene structure and separate donor/acceptor substituents. This segmentation allows independent optimization of each component's properties and simplifies the synthetic route by enabling modular assembly through standardized coupling reactions.
Solution Approach 2:
The absorption wavelength and fluorescent quantum yield are tuned by systematically varying substituent parameters on the xanthene core. By changing the type, position, and strength of electron-donating and electron-withdrawing groups, the molecular orbital energy gaps are adjusted to achieve absorption above 800 nm while maintaining acceptable fluorescence properties.
2Length of stationary object
If xanthene-based probes are designed to absorb light above 800 nm for deep tissue imaging, then imaging depth is improved, but fluorescent quantum yield decreases
Solution Approach 1:
Energy transfer intermediaries are introduced into the probe design, where the xanthene core acts as an antenna that absorbs NIR light and transfers energy to a fluorophore reporter group. This intermediary energy transfer mechanism enables the probe to utilize the deep-tissue-penetrating NIR wavelengths while the fluorophore emits at wavelengths suitable for detection, effectively decoupling the absorption and emission wavelength requirements.
Solution Approach 2:
The probe combines multiple functional moieties into a composite molecular structure: the xanthene chromophore for NIR absorption, donor/acceptor groups for enhancing charge transfer and stabilizing the excited state, and fluorogenic groups for signal generation. This composite design integrates the advantages of each component to achieve both deep tissue penetration and reliable fluorescence signal.
3Ease of manufacture
If conventional NIR probes are used, then synthesis is simplified, but photostability against biological agents decreases
Solution Approach 1:
The probe incorporates photoprotective groups and steric shielding around the reactive centers before exposure to biological environments. Electron-donating and electron-withdrawing groups are positioned to stabilize the excited state and prevent photo-induced degradation, while bulky substituents provide steric protection against nucleophilic attack by biological agents such as glutathione and esterases.
Solution Approach 2:
The chemical stability parameters of the probe are optimized by selecting substituents with appropriate electron-donating or electron-withdrawing strengths. These parameter adjustments modify the HOMO-LUMO energy gap and reduce the probe's susceptibility to oxidation, reduction, and hydrolysis, thereby enhancing photostability while maintaining synthetic accessibility through well-established substitution reactions.
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 novel NIR dye, XanthCR-880, achieves excellent photostability and detectable photoacoustic signals at depths up to 4 cm in tissue, offering improved imaging capabilities with enhanced molar absorptivity and stability against biological agents like glutathione and esterases.
Implementation Method 1
A state-of-the-art biomedical imaging technique is photoacoustic (PA) tomography that is characterized by the conversion of absorbed light to heat and then ultrasound waves via the photoacoustic effect
Implementation Method 2
Following irradiation of an optical absorber, the excited state can relax at a longer wavelength or lower energy via either by emission of a photon (fluorescence, Fl) or via non-radiative decay (photoacoustic)
Data Source
AI summary
A near infrared dye comprising a counterion and a structure of Formula Iwherein the at least one of R1 and R2are 1-(thiophen-2-yl)piperidine, 1-(thieno[3,2-b]thiophen-2-yl)piperidine or 1-([2,2′-bithiophen]-5-yl)piperidine, and X, R, R3-R4, R19, R20 and R22-R29 are disclosed herein. Materials and compositions comprising the NIR dye can absorb light in the NIR I & II regions and then the energy can be released in the form of light (fluorescence) or heat (non-radiative). The dyes can also convert the absorbed light to heat and ultrasound waves via the photoacoustic effect. The photoacoustic effect can be used in photoacoustic tomography to image biological materials or processes. Methods for synthesizing the NIR dyes and materials comprising the same are also disclosed.