Hydroxyapatite-Selective Fluorescent Dyes for Retinal Deposit Detection

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Solution Overview

Problem

Current diagnostic tools fail to detect age-related macular degeneration (AMD) and Alzheimer's disease before irreversible vision loss occurs, as they cannot identify hydroxyapatite deposits in the retina early enough for effective intervention.

Innovation Solution

The use of hydroxyapatite-selective fluorescent dyes, such as tetracycline derivatives, in combination with fluorescence lifetime imaging devices to detect hydroxyapatite deposits in the retina, which correlate with AMD and Alzheimer's disease, by binding to these deposits and exhibiting a longer fluorescence lifetime signal compared to background tissue.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional diagnostic tools are used, then the diagnostic process is simple and non-invasive, but they cannot detect hydroxyapatite deposits early enough for effective intervention

Engineering Contradiction:
Improvedetection sensitivityVSAvoiddiagnostic system complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent introduces fluorescent dyes as intermediary substances that specifically bind to hydroxyapatite deposits in the retina. These dyes act as mediators between the diagnostic system and the target deposits, enabling detection through fluorescence imaging. The dye molecules accumulate at the deposit sites and provide optical contrast that makes early deposits visible before they cause irreversible damage.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent utilizes fluorescence emission as an optical property change for detection. When fluorescent dyes bind to hydroxyapatite deposits, they emit characteristic fluorescence signals that can be detected by imaging devices. This optical property change allows differentiation between deposits and surrounding tissue, enabling early detection of AMD and Alzheimer's disease markers.

Inventive Principle:
Principle #32Color changes

2Loss of time

If fluorescence lifetime imaging is used to detect hydroxyapatite deposits, then early detection capability is improved, but the device complexity and cost increase

Engineering Contradiction:
Improvetime for early interventionVSAvoidimaging device complexity
Core Design Contradiction:
Loss of timeVSDevice complexity

Solution Approach 1:

The patent applies fluorescent dyes that bind to hydroxyapatite deposits before irreversible vision loss occurs. This preliminary detection allows intervention to be timed optimally - early enough to prevent damage but not so early that treatment would be ineffective. The fluorescence lifetime measurement provides a temporal signature that enables detection at this critical window of opportunity.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent replaces conventional mechanical or electrical diagnostic systems with an optical-based fluorescence lifetime imaging system. By using optical properties (fluorescence emission and lifetime) rather than mechanical or electrical measurements, the system achieves higher sensitivity for detecting early deposits while using non-invasive light-based techniques.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

3Measurement precision

If hydroxyapatite-selective fluorescent dyes are administered, then detection specificity is improved, but the procedure becomes more invasive

Engineering Contradiction:
Improvedetection specificityVSAvoidprocedure simplicity
Core Design Contradiction:
Measurement precisionVSEase of operation

Solution Approach 1:

The patent uses fluorescent dyes that exhibit different fluorescence properties when bound to hydroxyapatite versus when free in solution. This local change in fluorescence characteristics at the deposit sites provides high detection specificity. The dyes concentrate locally at the hydroxyapatite deposits, creating a localized signal that distinguishes deposits from surrounding healthy tissue.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The patent exploits changes in fluorescence lifetime as a parameter to detect hydroxyapatite deposits. When fluorescent dyes bind to hydroxyapatite, their fluorescence lifetime changes in a characteristic manner. By measuring this parameter change rather than just intensity, the system achieves high specificity for detecting deposits while using standard fluorescence imaging equipment.

Inventive Principle:
Principle #35Parameter changes

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

Enables early detection and monitoring of hydroxyapatite deposits, allowing for the prediction and diagnosis of AMD and Alzheimer's disease, potentially enabling timely intervention to prevent vision loss.

Implementation Method 1

hydroxyapatite-selective fluorescent dyes... binding to these deposits and exhibiting a longer fluorescence lifetime signal compared to background tissue

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Implementation Method 2

fluorescence lifetime imaging devices to detect hydroxyapatite deposits in the retina

Methodology Applied
Scientific EffectFluorescence lifetime imaging:

Data Source

PatentEP3504554B1Methods for detecting and/or predicting age-related macular degeneration and/or alzheimer's disease
Publication Date: 2024.04.03 UNIV OF MARYLAND
  • EP3504554B1 patent drawingFigure 1
  • EP3504554B1 patent drawingFigure 1
  • EP3504554B1 patent drawingFigure 2

AI summary

The present invention provides for the use of hydroxyapatite-selective fluorescent dyes in combination with fluorescence lifetime imaging to detect any hydroxyapatite spherules or hydroxyapatite deposits in the retina tissue of a subject, including the peripheral or macula tissue, wherein the hydroxyapatite spherules or hydroxyapatite deposits initiate or support the growth of sub-RPE deposits and correlates with age-related macular degeneration and/or Alzheimer's disease.