Fluorocarbon Microbubble Preparation with Narrow Size Distribution

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Current microbubble preparations for biomedical applications lack uniformity in size distribution and acoustic properties, making them inefficient for targeted therapeutic and diagnostic uses, as they often contain a non-homogenous mixture of microbubbles with varying diameters and acoustic responses to ultrasound.

Innovation Solution

A method for preparing fluorocarbon gas-filled microbubbles with a narrow size distribution and defined acoustic performance, involving the saturation of a serum albumin and dextrose solution with perfluorocarbon gas and the application of controlled ultrasound energy to produce microbubbles with specific diameter ranges and acoustic collapse thresholds.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If conventional microbubble preparation methods are used, then microbubbles can be produced quickly, but the size distribution is non-homogenous and acoustic properties vary

Engineering Contradiction:

Improvemicrobubble production speedVSAvoidsize distribution uniformity

Core Design Contradiction:

ProductivityVSManufacturing precision

Solution Approach 1:

The preparation method is divided into distinct sequential steps: gas saturation phase followed by ultrasonic exposure phase. This segmentation allows independent optimization of each phase - the saturation phase ensures uniform gas distribution throughout the solution, while the ultrasonic phase creates consistent microbubbles, thereby achieving narrow size distribution without sacrificing production efficiency

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The solution is pre-saturated with perfluorocarbon gas before ultrasonic exposure. This preliminary action ensures that gas is uniformly distributed and available throughout the solution during microbubble formation, leading to consistent nucleation and growth conditions that produce homogeneous microbubble sizes while maintaining high production rates

Inventive Principle:

Principle #10Preliminary action

2Manufacturing precision

If microbubbles are made with narrow size distribution, then acoustic performance is improved, but production complexity increases

Engineering Contradiction:

Improvesize distribution uniformityVSAvoidpreparation process complexity

Core Design Contradiction:

Manufacturing precisionVSDevice complexity

Solution Approach 1:

The method utilizes the inherent properties of the perfluorocarbon gas and the ultrasonic field to self-organize into uniform microbubbles. The gas saturation creates a uniform supersaturated solution that, when exposed to ultrasound, naturally forms microbubbles with consistent sizes through controlled cavitation, eliminating the need for complex external control mechanisms

Inventive Principle:

Principle #25Self-service

Solution Approach 2:

The method controls microbubble size and distribution by adjusting ultrasonic parameters (power level of 400-500 W, frequency of about 20 kHz, exposure duration) and gas saturation conditions. These parameter changes provide a simple yet effective means to achieve narrow size distribution without adding mechanical or procedural complexity to the system

Inventive Principle:

Principle #35Parameter changes

3Productivity

If microbubbles are exposed to ultrasonic energy, then microbubbles are formed, but acoustic collapse threshold varies

Engineering Contradiction:

Improvemicrobubble formation efficiencyVSAvoidacoustic collapse threshold consistency

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The method applies ultrasonic energy continuously for a defined period (20-30 seconds) at controlled power levels. This continuous exposure ensures complete and uniform cavitation throughout the saturated solution, forming microbubbles with consistent acoustic properties and collapse thresholds, while maintaining high formation efficiency through sustained energy input

Inventive Principle:

Principle #20Continuity of useful action

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 method results in microbubbles with a narrow size distribution and tailored acoustic properties, enabling them to withstand acoustic-induced collapse and maintain stability for extended periods, enhancing their effectiveness as therapeutic and diagnostic agents.

Implementation Method 1

saturating a solution comprising serum albumin and dextrose with the perfluorocarbon gas

Methodology Applied

Scientific EffectGas saturation: Absorption (physical)

Implementation Method 2

delivering a first round of ultrasound energy within the solution

Methodology Applied

Scientific EffectAcoustic cavitation: Acoustic Cavitation

Implementation Method 3

acoustic-induced collapse

Methodology Applied

Scientific EffectCavitation: Cavitation

Data Source

PatentUS9023321B2Methods for producing microbubbles

Publication Date: 2015.05.05 BIOVENTURES LLC

AI summary

The present invention provides methods for the preparation of gas-filled microbubbles, and methods of using for therapeutic and/or diagnostic applications. In particular, the methods of the invention allow for the preparation of gas-filled microbubbles having narrow size distributions and defined ultrasonic properties.