Acoustically Activatable Particles for Ultrasound Imaging
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Solution Overview
Problem
Current microbubble contrast agents for ultrasound imaging are trapped within the circulatory system due to their size, preventing extravasation into interstitial spaces, and require excessive ultrasonic energy for activation, which can cause tissue damage, making them unsuitable for therapeutic and diagnostic applications that require smaller particles for effective tissue imaging and treatment.
Innovation Solution
Development of acoustically activatable nanoparticles and micro-particles using high volatility perfluorocarbons (PFCs) encapsulated in lipid or polymer shells, which remain stable at physiological temperatures and can be activated using clinically relevant ultrasound frequencies, allowing for extravasation and expansion into bubbles for enhanced imaging and therapeutic delivery.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If microbubble contrast agents are used for ultrasound imaging, then imaging capability is improved, but the particles cannot extravasate into interstitial spaces due to their size
Solution Approach 1:
The particles are designed to dynamically change their size in response to acoustic stimulation. They circulate as small nanoparticles (100-750 nm) that can extravasate through endothelial gaps, then expand into larger microbubbles upon ultrasound activation for enhanced imaging and therapeutic effect
Solution Approach 2:
The physical state and dimensions of the particles are changed through acoustic energy input. The transition from nanoparticle to microbubble involves changing key parameters including size, volume, and acoustic impedance to achieve both extravasation capability and imaging performance
2Productivity
If ultrasonic energy is increased to activate particles, then activation efficiency is improved, but tissue damage occurs due to excessive energy
Solution Approach 1:
The particles utilize phase transition from liquid to gas upon acoustic activation. This phase change occurs at lower energy thresholds compared to direct mechanical disruption, enabling efficient activation while reducing the risk of cavitation-induced tissue damage
Solution Approach 2:
The particle shell acts as an intermediary that mediates the energy transfer from ultrasound to the core material. The shell protects surrounding tissue from direct exposure to high-energy cavitation while facilitating controlled activation of the particle
3Length of moving object
If particle size is reduced for extravasation, then tissue penetration is improved, but activation energy requirements increase
Solution Approach 1:
The particles are constructed as composite structures with a core-shell architecture. The core contains the gas-forming material while the shell provides structural stability and acoustic sensitivity, enabling small size for extravasation while maintaining low activation energy requirements through optimized material composition
Solution Approach 2:
Different regions of the particle have specialized properties: the core is designed for low-energy phase transition while the shell provides mechanical stability and acoustic responsiveness. This local differentiation allows the particle to maintain small size without proportionally increasing activation energy requirements
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 approach enables the creation of stable nanoparticles that can extravasate into tissues and be activated with lower energy, providing effective ultrasound contrast and therapeutic delivery while minimizing tissue damage, and can be used for diagnostic imaging, drug delivery, and targeted treatments.
Implementation Method 1
acoustically activatable particles... ADV acoustic droplet vaporization... providing activation energy sufficient to cause the liquid within the encapsulated droplets to change from a liquid phase to a gas phase
Implementation Method 2
A second substance, different from the first substance, encapsulates the first substance to create a droplet or emulsion that is stable at room temperature and atmospheric pressure
Data Source
AI summary
Acoustically activatable particles having low vaporization energy and methods for making and using same are disclosed. A particle of material includes a first substance that includes at least one component that is a gas 25° C. and atmospheric pressure. A second substance, different from the first substance, encapsulates the first substance to create a droplet or emulsion that is stable at room temperature and atmospheric pressure. At least some of the first substance exists in a gaseous phase at the time of encapsulation of the first substance within the second substance to form a bubble. After formation of the bubble, the bubble is condensed into a liquid phase, which causes the bubble to transform into the droplet or emulsion having a core consisting of a liquid. The droplet or emulsion is an activatable phase change agent that remains a droplet having a core consisting of a liquid at 25° C. and atmospheric pressure. The first substance has a boiling point below 25° C. at atmospheric pressure.