HYPDX-4 Fluorescent Probe for Retinal Hypoxia Imaging
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Solution Overview
Problem
Current methods for detecting retinal hypoxia in living systems are invasive, indirect, or not suitable for real-time imaging, limiting the ability to effectively monitor and treat blinding retinal vascular diseases such as age-related macular degeneration, retinopathy of prematurity, and retinal vein occlusion.
Innovation Solution
Development of hypoxia-sensitive fluorescence imaging agents like HYPDX-4, which are selectively retained in hypoxic retinal cells, allowing for non-invasive, in vivo imaging of retinal hypoxia through dose-dependent fluorescence enhancement and high signal-to-noise ratios, facilitating early detection and monitoring of retinal diseases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If oxygen sensitive electrodes are used to measure retinal oxygen pressure, then reliable data can be acquired, but the method is invasive and cannot be used for rodents due to their small globes
Solution Approach 1:
The patent replaces the mechanical/electrical oxygen electrode system with a fluorescent optical sensing system. The fluorescent probe HYPDX-4 detects oxygen levels through fluorescence intensity changes, eliminating the need for physical electrodes and enabling non-invasive measurements in small animal models while maintaining measurement reliability
Solution Approach 2:
The patent changes the measurement parameter from electrical signal (electrode potential) to optical signal (fluorescence intensity). This parameter transformation allows the use of non-invasive optical methods while preserving the ability to accurately measure oxygen pressure in retinal tissue
2Ease of operation
If nuclear magnetic resonance is used to measure oxygen tension, then the method is minimally invasive, but the resolution is appreciably less than optical methods
Solution Approach 1:
The patent replaces NMR with fluorescent optical sensing, combining the minimally invasive nature of optical methods with superior spatial resolution. The fluorescent probe provides cellular-level resolution while maintaining minimal invasiveness, outperforming both NMR and electrode methods
3Ease of operation
If retinal oximetry or doppler OCT is used to measure oxygen levels, then measurements can be performed in living systems, but the methods are indirect and mathematical modeling is required to estimate perivascular oxygen pressure
Solution Approach 1:
The patent replaces indirect optical methods (oximetry, Doppler OCT) with direct fluorescent sensing at the tissue level. The fluorescent probe HYPDX-4 directly measures interstitial oxygen pressure through fluorescence quenching, eliminating the need for mathematical modeling while maintaining in vivo capability
Solution Approach 2:
The patent introduces a fluorescent probe intermediary that directly interacts with oxygen molecules in the retinal tissue. This probe serves as a direct sensor of oxygen pressure, replacing the indirect hemoglobin-based measurements and eliminating the need for complex mathematical transformations
4Measurement precision
If phosphorescent quenching is used to assess oxygen pressure, then intravascular oxygen levels can be measured, but only limited assessment of oxygen pressure in retinal tissue is provided
Solution Approach 1:
The patent replaces phosphorescent quenching with fluorescent sensing using HYPDX-4. The fluorescent probe provides both accurate oxygen detection and comprehensive tissue coverage, overcoming the limitation of phosphorescent methods that are restricted to intravascular assessment
Solution Approach 2:
The patent changes from phosphorescence to fluorescence detection, utilizing different photophysical properties. The fluorescent probe HYPDX-4 offers both high oxygen sensitivity and the ability to assess oxygen pressure throughout the entire retinal tissue, not just intravascular spaces
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
HYPDX-4 enables non-invasive, real-time imaging of retinal hypoxia in preclinical and human models, providing valuable insights into disease progression and therapy efficacy, while being non-toxic and capable of detecting hypoxia before overt neural or vascular anomalies.
Implementation Method 1
HYPDX-4 is a fluorescent probe that exhibits dose-dependent fluorescence enhancement in response to decreasing oxygen levels
Implementation Method 2
oxygen-dependent molecular phosphorescence quenching
Data Source
AI summary
A compound and method for detecting hypoxic cells and tissue are provided. The compound includes a probe selected from the group consisting of a hypoxia sensitive 2-nitroimidazole containing fluorescence imaging probe, a hypoxia sensitive reversible ON-OFF fluorescence imaging probe, a hypoxia sensitive azo-based fluorescence imaging probe, and combinations thereof. The method includes contacting the cells or tissue with the probe of any one of claims 1-13 and detecting fluorescent intensity of the cell or tissue, wherein increased fluorescent intensity indicates that the cells or tissue is hypoxic. Also provided are a method of synthesizing the compound and a method for synthesizing a therapeutic agent including the compound.