Transient Microbubble Generation for Precision Drug Delivery

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Solution Overview

Problem

Current acoustically activated drug delivery systems lack flexibility for administering various drugs or drug combinations on short notice with improved drug uptake and reduced side effects, particularly in treating drug-resistant cancers and deep-tissue diseases.

Innovation Solution

A medical device and method for generating transient micro or nano bubbles using in-line capillary tubes and cross flow bubble generation, with stabilization through rectified diffusion, enabling precision direct drug delivery, combined inertial and non-inertial acoustic activation, and enhanced ultrasound ablation for localized treatment.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If persistent hard-shelled gas microbubbles are used for drug delivery, then the bubbles can maintain integrity through transportation and storage, but they require complex polymer formulations and must dissipate or degrade in the patient with minimal negative side effects

Engineering Contradiction:

Improvebubble integrity during storage and transportationVSAvoidcomplex polymer formulation and processing features

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent employs transient microbubbles that are generated immediately before administration and dissipate quickly in the patient's body. These short-living bubbles eliminate the need for complex persistent formulations, using simple gas-liquid mixtures instead of polymer-based systems. The transient nature of the bubbles means they don't require the same level of structural integrity maintenance during storage and transportation.

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

Solution Approach 2:

The patent pre-mixes gas and liquid components in a sealed container before administration, creating a stable mixture that can be stored and transported. The actual bubble formation occurs only when the mixture is administered to the patient and exposed to ultrasound activation, eliminating the need for complex formulations to maintain bubble integrity throughout the entire storage and transportation period.

Inventive Principle:

Principle #10Preliminary action

2Manufacturing precision

If transient microbubbles are generated using in-line capillary tubes and cross flow bubble generation, then uniform bubbles can be produced for enhanced ultrasound activation, but the system requires precise control of fluid flow and bubble formation

Engineering Contradiction:

Improvebubble size uniformity and homogeneityVSAvoidprecise control systems for fluid flow and bubble generation

Core Design Contradiction:

Manufacturing precisionVSDevice complexity

Solution Approach 1:

The patent utilizes pneumatic and hydraulic principles to control bubble formation. Gas flow through capillary tubes and cross-flow channels creates uniform bubbles through pressure differential and flow dynamics. The system uses simple fluid pressure control rather than complex electronic control systems to achieve precise bubble size uniformity, leveraging the natural behavior of fluids under pressure to generate homogeneous bubble distributions.

Inventive Principle:

Principle #29Pneumatics and hydraulics

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 system allows for flexible, precise, and effective delivery of therapeutic agents with reduced side effects by generating uniform bubbles for enhanced ultrasound activation, improving treatment efficacy and expanding the use of photodynamic drugs and high-intensity focused ultrasound treatments.

Implementation Method 1

a fluid delivery means operatively connected to the fluid vessel for applying a pressure and causing the fluid to travel a flow path

Methodology Applied

Scientific EffectPressure gradient: Pressure Gradient

Implementation Method 2

bubble stability through rectified diffusion

Methodology Applied

Scientific EffectRectified diffusion: Diffusion

Implementation Method 3

Ultrasound energy may cause gas microbubbles to resonate or burst into smaller fragments, and may induce cavitation, microstreaming, or the perforation of cell membranes

Methodology Applied

Scientific EffectAcoustic cavitation: Acoustic Cavitation

Implementation Method 4

Bubble resonance is typically described as sonoporation or non-inertial cavitation

Methodology Applied

Scientific EffectResonance: Resonance

Implementation Method 5

Acoustic activation or sonoporation of the bubbles, through the application of ultrasound energy, increases cell permeability and improves drug uptake and treatment efficacy

Methodology Applied

Scientific EffectSonoporation:

Data Source

PatentUS8679051B2Microbubble medical devices

Publication Date: 2014.03.25 ARTENGA

AI summary

Method and medical devices for generating and stabilizing micro- or nano-bubbles, and systems and methods for therapeutic applications using the bubbles, are provided. The micro-bubbles may be used to enhance therapeutic benefits such as ultrasound-guided precision drug delivery and real-time verification, acoustic activation of large tumor masses, enhanced acoustic activation through longer retention of therapeutic agents at the point of interest, enhancement of high intensity focused ultrasound treatments, light activation of photodynamic drugs at a depth within a patient using extracorporeal light sources, probes, or sonoluminescence, and initiation of time reversal acoustics focused ultrasound to permit highly localized treatment.