Coated Bismuth Nanoparticles for Stable X-ray Contrast

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Solution Overview

Problem

Current X-ray contrast agents, particularly gold nanoparticles, face challenges due to high cost, biological and environmental toxicity, and instability in aqueous environments, making them unsuitable for large-scale medical use. Additionally, existing radiopaque materials like iopromide, barium sulfate, tin, and lead have limitations, especially in particle form and stability.

Innovation Solution

Development of radiopaque bismuth particles with an elemental core coated with hydrophilic, hydrophobic, or amphiphilic agents to enhance stability and dispersion in various matrices, using either 'top-down' or 'bottom-up' synthesis methods, which include mechanical mixing or solubilization with reducing agents to form coated bismuth particles suitable for biomedical and industrial applications.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If gold nanoparticles are used as X-ray contrast agents, then ease of synthesis and morphological control are improved, but cost increases and biological toxicity risks worsen

Engineering Contradiction:
Improveease of synthesisVSAvoidbiological toxicity
Core Design Contradiction:
Ease of manufactureVSObject-affected harmful factors

Solution Approach 1:

The patent changes the material parameter from gold to bismuth, maintaining the nanoparticle form factor while altering the elemental composition to achieve lower toxicity and cost. This parameter substitution resolves the contradiction by preserving the beneficial ease of synthesis while eliminating the harmful biological toxicity associated with gold nanoparticles.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent employs bismuth nanoparticles as a cheaper alternative to gold nanoparticles. Bismuth is significantly less expensive than gold while providing comparable X-ray attenuation properties. The nanoparticles are designed to be biodegradable and excretable, replacing the persistent gold nanoparticles that pose long-term toxicity risks.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

2Quantity of substance

If gold nanoparticles larger than 5 nm are used, then X-ray attenuation capability is improved, but biological and environmental toxicity risk worsens due to bio-accumulation

Engineering Contradiction:
ImproveX-ray attenuation capabilityVSAvoidbio-accumulation toxicity
Core Design Contradiction:
Quantity of substanceVSObject-affected harmful factors

Solution Approach 1:

The patent changes the material parameter from gold to bismuth while maintaining nanoparticle sizes larger than 5 nm for optimal X-ray attenuation. Bismuth's higher atomic number (Z=83) compared to gold (Z=79) provides superior X-ray attenuation per unit mass, allowing the use of larger particles that can be more easily cleared by biological systems without accumulating.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent designs bismuth nanoparticles to be transient rather than persistent in biological systems. Unlike gold nanoparticles that accumulate indefinitely, bismuth nanoparticles are engineered to be biodegradable and excretable, with a finite lifetime in the body that prevents bio-accumulation while maintaining sufficient X-ray attenuation during the imaging window.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

3Area of moving object

If nanosize particles are used to increase surface area, then unique properties are improved, but stability in aqueous environments worsens due to oxidative degradation

Engineering Contradiction:
Improvesurface areaVSAvoidaqueous stability
Core Design Contradiction:
Area of moving objectVSStability of the object's composition

Solution Approach 1:

The patent creates a composite structure consisting of a bismuth nanoparticle core coated with a protective shell. The core provides the desired high surface area for unique properties, while the protective coating (such as polymers, surfactants, or oxides) forms a barrier that prevents direct contact between the bismuth surface and aqueous environment, thereby preventing oxidative degradation while preserving the beneficial high surface area characteristics.

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 coated bismuth particles provide stable, tunable, and highly X-ray attenuating dispersions, suitable for biomedical imaging and industrial uses, offering biocompatibility, cost-effectiveness, and improved stability in aqueous environments, overcoming the limitations of existing contrast agents.

Implementation Method 1

The coating agents are alcohols, aliphatic compounds, alkylquinolinium cations, amines, aryl compounds, carbohydrates, carboxylic acids, ketones, aldehydes, thiocarboxylic acids, organothiols, polymers, perhalogenated alkyl phosphonates, perhalogenated alkyl siloxanes and combinations thereof. In some embodiments, the coating agents stabilize the nanoparticle against oxidative degradation

Methodology Applied
Scientific EffectAdsorption: Adsorption

Implementation Method 2

most metals are susceptible to the formation of oxides on their surface, which can lead to the eventual oxidative degradation of the material. This makes the stabilization of aqueous metal nanomaterials difficult

Methodology Applied
Scientific EffectOxidation: Oxidation

Implementation Method 3

adding a reducing agent to the solubilized bismuth solution to reduce bismuth ions and form elemental bismuth particles

Methodology Applied
Scientific EffectRedox Reactions: Redox Reactions

Data Source

PatentEP3492116B1Bismuth particle x-ray contrast agents
Publication Date: 2022.03.23 PORTLAND STATE UNIV
  • EP3492116B1 patent drawingFigure 1a~3
  • EP3492116B1 patent drawingFigure 4~6
  • EP3492116B1 patent drawingFigure 7~8

AI summary

Radiopaque bismuth particles and methods of making and using the radiopaque bismuth particles are disclosed. The radiopaque bismuth particles include an elemental bismuth core and an outer coating comprising one or more coating agents. Disclosed radiopaque bismuth particles are suitable for use in surgical sponges and plastic objects.