Fluorescent Gold Nanocluster Microbubble Contrast Agent

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Solution Overview

Problem

Current medical contrast agents for biomedical imaging, such as microbubbles, lack multifunctionality and advanced imaging capabilities, particularly in enhancing contrast for both ultrasonography and fluorescein angiography.

Innovation Solution

Development of microbubbles with a shell composed of fluorescent Au nanoclusters surrounded by albumin layers, which can be further protected by additional ligands, allowing for enhanced fluorescence and improved imaging capabilities.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If traditional microbubbles with albumin or lipid shells are used, then ultrasonography contrast enhancement is achieved, but fluorescence imaging capability is lacking

Engineering Contradiction:
Improveimaging modality versatilityVSAvoidcontrast enhancement reliability
Core Design Contradiction:
Adaptability or versatilityVSReliability

Solution Approach 1:

The microbubble shell is designed to contain both albumin molecules and fluorescent Au nanoclusters, enabling the single contrast agent to function in both ultrasonography (via microbubble backscattering) and fluorescence imaging (via Au nanocluster fluorescence), thus achieving multi-functionality and resolving the contradiction between versatility and reliability

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

Solution Approach 2:

The shell comprises a composite structure integrating albumin proteins with fluorescent Au nanoclusters, combining the acoustic scattering properties of traditional microbubbles with the fluorescent properties of gold nanoclusters, thereby maintaining reliable ultrasonography contrast while adding fluorescence imaging capability

Inventive Principle:
Principle #40Composite materials

2Adaptability or versatility

If Au nanoclusters are incorporated into the microbubble shell, then fluorescence imaging capability is enhanced, but shell stability may be compromised

Engineering Contradiction:
Improvefluorescence imaging capabilityVSAvoidshell structural stability
Core Design Contradiction:
Adaptability or versatilityVSStability of the object's composition

Solution Approach 1:

The Au nanoclusters are nested within the albumin shell structure, with each nanocluster surrounded by albumin molecules that provide structural support and stability. This nested configuration allows the fluorescent nanoclusters to be protected while maintaining the overall shell integrity for reliable ultrasonography

Inventive Principle:
Principle #7Nested doll (Nesting)

Solution Approach 2:

Albumin molecules serve as intermediary structures that bind to and stabilize the Au nanoclusters within the shell, mediating between the nanoclusters and the microbubble structure to maintain shell stability while enabling fluorescence imaging functionality

Inventive Principle:
Principle #24Intermediary (Mediator)

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 microbubbles provide enhanced contrast for both ultrasonography and fluorescein angiography, offering improved imaging capabilities and potential for multifunctional biomedical applications.

Implementation Method 1

Au3+ is reduced by adding a base into the mixing solution to form the Au nanocluster-albumin complex

Methodology Applied
Scientific EffectReduction: Reduction

Implementation Method 2

The dispersed solution is sonicated at an ultrasound intensity of about 11-24 watts for about 1-3 minutes to form microbubbles

Methodology Applied
Scientific EffectUltrasonic vibration: Ultrasonic Vibration

Implementation Method 3

The density on the interface between the gas in the bubble and the surrounding liquid strongly scatters and reflects the ultrasound back to the probe

Methodology Applied
Scientific EffectBackscattering: Scattering

Implementation Method 4

microbubbles containing fluorescent Au nanoclusters

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Data Source

PatentUS9523032B2Medical contrast agent made of microbubbles containing fluorescent gold nanoclusters
Publication Date: 2016.12.20 CHUNG YUAN CHRISTIAN UNIVERSITY
  • US9523032B2 patent drawing
  • US9523032B2 patent drawing
  • US9523032B2 patent drawing

AI summary

A medical contrast agent made of microbubbles containing Au nanoclusters is provided. The shell of the microbubbles contains fluorescent Au nanocluster-albumin complex, and the core contains air or fluorocarbons. The method for preparing the microbubbles is also disclosed.