Composite Probe for Enzyme Metallographic Detection

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Solution Overview

Problem

Current biological detection methods face challenges in visualizing multiple targets simultaneously due to the limitations of black metallographic signals, which obscure overlapping stains, and the need for multiple labeling and detection procedures, compromising specimen integrity and resolution.

Innovation Solution

A composite probe comprising a directing agent, gold nanoparticles, and a redox active enzyme, which reacts with an enzyme substrate to produce a visible signal, allowing for simultaneous enzymatic and gold labeling in a single procedure, enabling enhanced sensitivity and correlation of information at different resolution levels.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If metallographic labeling is used for detection, then sensitivity and specificity are improved, but the black opaque signal obscures overlapping stains and prevents spectral imaging

Engineering Contradiction:
Improvedetection sensitivityVSAvoidspectral imaging capability
Core Design Contradiction:
Measurement precisionVSAdaptability or versatility

Solution Approach 1:

The patent applies color changes by using gold nanoparticles that can be visualized at different wavelengths. The gold nanoparticles provide a spectral signal that can be detected across multiple wavelengths, allowing the system to distinguish between different targets based on their spectral signatures rather than relying on opaque black deposits. This enables spectral imaging while maintaining the high sensitivity of metallographic detection.

Inventive Principle:
Principle #32Color changes

2Adaptability or versatility

If multiple labeling and detection procedures are used to detect multiple targets, then detection capability is improved, but specimen integrity is compromised and resolution is reduced

Engineering Contradiction:
Improvemulti-target detection capabilityVSAvoidspecimen integrity
Core Design Contradiction:
Adaptability or versatilityVSManufacturing precision

Solution Approach 1:

The patent merges multiple labeling and detection procedures into a single procedure by using composite probes that combine gold nanoparticles with enzymes or other detection molecules. This allows multiple targets to be detected simultaneously in one labeling step, maintaining specimen integrity and resolution while improving multi-target detection capability.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The patent applies universality by creating multi-functional probes that can detect multiple targets simultaneously. The gold nanoparticle-based probes can be designed to recognize different antigens or molecular targets, allowing a single probe system to perform multiple detection functions without requiring separate labeling procedures for each target.

Inventive Principle:
Principle #6Universality (Multi-functionality)

3Measurement precision

If black metallographic signals are used for visualization, then detection sensitivity is improved, but overlapping targets cannot be resolved spectrally

Engineering Contradiction:
Improvedetection sensitivityVSAvoidspectral resolution of overlapping signals
Core Design Contradiction:
Measurement precisionVSDifficulty of detecting and measuring

Solution Approach 1:

The patent uses gold nanoparticles that exhibit characteristic spectral properties rather than producing opaque black signals. The gold nanoparticles can be detected across multiple wavelengths, creating a spectral signature that enables differentiation between overlapping targets based on their wavelength-specific signals, thus resolving the spectral resolution problem while maintaining detection sensitivity.

Inventive Principle:
Principle #32Color 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

This approach facilitates the detection of multiple targets with increased sensitivity and resolution, allowing for correlative fluorescence or brightfield optical staining and electron microscopic labeling, without requiring multiple labeling operations, and provides higher detection sensitivity and improved visualization of biological targets.

Implementation Method 1

a redox active enzyme, for reacting with an enzyme substrate after the composite probe is bound to the target

Methodology Applied
Scientific EffectRedox reactions: Redox Reactions

Implementation Method 2

at least one nanoparticle conjugated to the at least one directing agent, the at least one nanoparticle comprising a plurality of gold atoms

Methodology Applied
Scientific EffectLight absorption: Absorption (EM radiation)

Data Source

PatentEP2269065B1Methods and reagents to increase the sensitivity of enzyme metallographic detection
Publication Date: 2017.11.22 NANOPROBES
  • EP2269065B1 patent drawingFigure 1~2b
  • EP2269065B1 patent drawingFigure 3a~3d
  • EP2269065B1 patent drawingFigure 4a~4b

AI summary

A test agent includes a composite probe having at least one nanoparticle having multiple metal atoms, a directing agent, and an enzyme. The directing agent attaches the probe to a target in a test sample. The test sample and bound probe are then treated with an enzyme substrate. A method of detecting a target in a test sample includes exposing the test sample to the probe, then treating the test sample with an enhancement or development solution to deposit at least one of a fluorophore, a chromgen, or a metal.