Magnetic Microbubble Thrombolysis via Rotational Field

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Solution Overview

Problem

Current ultrasound thrombolysis methods using microbubbles have low efficiency due to low microbubble concentration at the clot region caused by reduced blood flow, limiting the effectiveness of clot dissolution in blood vessels.

Innovation Solution

The use of magnetic microbubbles (MMBs) with a gas core and a layer of superparamagnetic nanoparticles, combined with a rotational magnetic field and ultrasound transducer, to enhance cavitation and accumulation of MMBs at the clot site, along with nanodroplets for improved thrombolysis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If conventional microbubbles are used for ultrasound thrombolysis, then the treatment can be administered, but the microbubble concentration at the clot region is low due to reduced blood flow, resulting in low lysis efficiency

Engineering Contradiction:

Improvethrombolysis rateVSAvoidmicrobubble concentration at clot region

Core Design Contradiction:

ProductivityVSQuantity of substance

Solution Approach 1:

Magnetic microbubbles serve as an intermediary carrier that can be actively transported to the clot region using external magnetic fields, overcoming the limitation of passive blood flow. The magnetic nanoparticles embedded in the microbubble shell enable responsive accumulation at the target site, significantly increasing local concentration and subsequent lysis efficiency.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

External magnetic fields are applied in advance to pre-accumulate magnetic microbubbles at the clot region before ultrasound activation. This preliminary positioning ensures high microbubble concentration is achieved at the target site, resolving the issue of low concentration caused by reduced blood flow.

Inventive Principle:

Principle #10Preliminary action

2Quantity of substance

If higher microbubble concentration is achieved through passive blood flow, then more microbubbles reach the clot, but reduced blood flow in the vessel limits the concentration that can be achieved

Engineering Contradiction:

Improvemicrobubble concentrationVSAvoidblood flow speed

Core Design Contradiction:

Quantity of substanceVSSpeed

Solution Approach 1:

Magnetic fields act as an intermediary force to transport microbubbles to the clot region, replacing reliance on blood flow speed. This external force mechanism enables high concentration accumulation independent of the reduced blood flow conditions in occluded vessels.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The natural mechanical blood flow system is replaced with an external magnetic field system for microbubble transport. This substitution allows precise control of microbubble delivery to the clot region without being constrained by the speed or volume of blood flow.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

3Productivity

If rt-PA is used for thrombolysis, then clot dissolution can be achieved, but off-target effects such as increased risk of intracranial hemorrhage occur

Engineering Contradiction:

Improveclot dissolution effectivenessVSAvoidrisk of intracranial hemorrhage

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The magnetic microbubble system enables localized thrombolysis by concentrating microbubbles specifically at the clot region using external magnetic fields. This spatially selective approach ensures that ultrasound activation and subsequent clot dissolution occur only at the target site, preventing systemic off-target effects such as intracranial hemorrhage.

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

Magnetic fields serve as a localized intermediary that delivers therapeutic effect precisely to the clot region without affecting other areas of the body. This targeted delivery mechanism replaces the systemic action of rt-PA with a localized physical field approach, eliminating harmful off-target effects.

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

This approach significantly increases the thrombolysis rate by enhancing microbubble cavitation and nanodroplet permeation into the clot fibrin network, achieving partial or complete clot dissolution with lower ultrasound exposure.

Implementation Method 1

a rotational magnetic field generator effective to accumulate MMBs in a target region

Methodology Applied

Scientific EffectMagnetic field: Magnetic Field

Implementation Method 2

an ultrasound transducer effective to induce cavitation of the MMBs

Methodology Applied

Scientific EffectAcoustic cavitation: Acoustic Cavitation

Implementation Method 3

increase cavitation of the MMBs induced by the ultrasound transducer

Methodology Applied

Scientific EffectMagnetic field: Magnetic Field

Data Source

PatentUS11883679B2Systems and methods for ultrasound induced thrombolysis with magnetic microbubbles, optional nanodroplets, and a rotational magnetic field

Publication Date: 2024.01.30 NORTH CAROLINA STATE UNIV

AI summary

The disclosure provides systems for ultrasound-induced thrombolysis with magnetic microbubbles under a rotational/alternating magnetic field, sonothrombolysis systems with magnetic microbubbles and optional nanodroplets for inducing thrombolysis under an acoustic field, and a rotational/alternating magnetic field, and methods of treating patients with blood clots using the sonothrombolysis systems of the present disclosure.