Room-Temperature Phosphorescence Nanoparticles for Retinal Hypoxia Imaging

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Solution Overview

Problem

Current methods for detecting ischemia-induced retinal hypoxia, such as oxygen-sensitive microelectrodes, MRI, dual wavelength retinal oximetry, and fluorescence/phosphorescence imaging, have limitations including invasive procedures, insufficient resolution, and inability to measure oxygen tension outside retinal blood vessels, leading to a need for a non-destructive, effective method for long-term visualization and quantification of tissue hypoxia.

Innovation Solution

Development of room-temperature phosphorescence nanoparticles with a metal-free organic phosphor embedded in a hydrophobic, glassy, and oxygen-permeable polymer core, surrounded by a lipid shell, allowing for real-time visualization of chorioretinal tissue hypoxia with high spatiotemporal resolution and biocompatibility.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If oxygen-sensitive microelectrodes are used for hypoxia detection, then measurement precision is improved, but the procedure becomes invasive and requires implantation

Engineering Contradiction:

Improvehypoxia detection precisionVSAvoidinvasiveness

Core Design Contradiction:

Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The patent replaces the mechanical microelectrode implantation system with an optical imaging system using phosphorescent nanoparticles. The nanoparticles are administered systemically and accumulate in target tissues, where their phosphorescence signal is detected optically to map oxygen tension distributions without mechanical intrusion into the tissue.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent introduces phosphorescent nanoparticles as an intermediary substance that mediates between the oxygen environment and the detection system. These nanoparticles serve as oxygen-sensitive probes that can be administered non-invasively and provide optical signals proportional to local oxygen tension, eliminating the need for direct electrode-tissue contact.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Area of stationary object

If MRI is used for hypoxia imaging, then field of view and depth information are improved, but resolution is insufficient to identify small areas of focal hypoxia

Engineering Contradiction:

Improvefield of viewVSAvoidspatial resolution

Core Design Contradiction:

Area of stationary objectVSMeasurement precision

Solution Approach 1:

The patent changes the detection parameter from MRI's macroscopic magnetic resonance signals to optical phosphorescence signals at the nanoscale. This parameter change enables much higher spatial resolution because optical detection can resolve fine structural details that are below the diffraction limit of MRI, while still providing tissue-wide coverage through appropriate nanoparticle distribution.

Inventive Principle:

Principle #35Parameter changes

3Measurement precision

If retinal oximetry is used to measure oxygen saturation, then accuracy in large vessels is improved, but it cannot detect dynamic changes in microaneurysms or capillaries

Engineering Contradiction:

Improveoxygen saturation measurement accuracyVSAvoidapplicability to microvasculature

Core Design Contradiction:

Measurement precisionVSAdaptability or versatility

Solution Approach 1:

The patent segments the measurement approach by using nanoparticle probes that can access and report oxygen tension in individual microvascular units, capillaries, and tissue compartments separately. This segmentation enables independent measurement of oxygen dynamics in different vascular beds and tissue regions, providing versatility across multiple scales from large vessels to microaneurysms.

Inventive Principle:

Principle #1Segmentation

4Measurement precision

If fluorescence and phosphorescence imaging is used for oxygen tension measurement, then optical resolution is improved, but long-term visualization is not possible due to rapid clearance of small molecule dyes

Engineering Contradiction:

Improveoxygen tension measurement precisionVSAvoidlong-term visualization capability

Core Design Contradiction:

Measurement precisionVSDuration of action of stationary object

Solution Approach 1:

The patent uses composite nanoparticle materials consisting of phosphorescent probes embedded in biocompatible polymer matrices or lipid structures. This composite design combines the oxygen-sensing capability of phosphorescent molecules with the extended circulation half-life and reduced clearance characteristics of nanoparticle carriers, enabling long-term in vivo imaging while maintaining measurement precision.

Inventive Principle:

Principle #40Composite materials

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 nanoparticles enable non-destructive, real-time imaging of retinal tissue hypoxia with high signal-to-noise ratio and long-term stability, effectively detecting oxygen gradients and tissue hypoxia, overcoming the limitations of existing techniques.

Implementation Method 1

based on oxygen-dependent quenching of fluorescence or phosphorescence

Methodology Applied

Scientific EffectOxygen-dependent quenching of phosphorescence: Phosphorescence

Implementation Method 2

hydrophobic, glassy, and oxygen-permeable polymer

Methodology Applied

Scientific EffectPermeation: Permeation

Data Source

PatentUS20240000976A1Room-temperature phosphorescence nanoparticles and methods of making the same

Publication Date: 2024.01.04 THE RGT UNIV OF MICHIGAN

AI summary

Provided herein are room-temperature phosphorescence nanoparticles, methods of preparing the same, and uses of the same.