Porphyrin-Phospholipid Microbubble Shell Stability and Imaging

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Solution Overview

Problem

Current microbubbles used in ultrasound imaging have stability issues due to the incorporation of fluorophores, which affect the shell's integrity and longevity, and lack optimal multimodal imaging capabilities.

Innovation Solution

Development of microbubbles with a porphyrin-phospholipid shell, where porphyrin is covalently attached to a lipid side chain, forming a monolayer with a PEGylated emulsifier, enhancing stability and multimodal imaging properties.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If fluorophores are incorporated into the microbubble shell to verify binding and disruption, then imaging capability is improved, but microbubble shell stability deteriorates

Engineering Contradiction:
Improveimaging capabilityVSAvoidmicrobubble shell stability
Core Design Contradiction:
Ease of manufactureVSStability of the object's composition

Solution Approach 1:

The patent uses porphyrin-phospholipid conjugates as composite materials that combine the structural properties of phospholipids with the imaging properties of porphyrins. This integration allows the shell to maintain stability while providing robust intrinsic multimodal imaging capabilities through fluorescence, photoacoustic, MR and PET imaging modes.

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

The patent merges the structural function of phospholipid shells with the imaging function of porphyrins by covalently attaching porphyrin to the phospholipid side chain. This creates a unified material that simultaneously provides both shell integrity and imaging capability, eliminating the need to add separate fluorophore molecules that would compromise stability.

Inventive Principle:
Principle #5Merging (Combining)

2Stability of the object's composition

If porphyrin-phospholipid conjugate is used to form the microbubble shell, then stability and shell stiffness are improved, but device complexity increases

Engineering Contradiction:
Improvemicrobubble shell stabilityVSAvoidshell structure complexity
Core Design Contradiction:
Stability of the object's compositionVSDevice complexity

Solution Approach 1:

The patent modifies the chemical structure of phospholipids by attaching porphyrin groups to their side chains at specific positions (sn-1 or sn-2). This parameter change in the molecular structure provides both enhanced stability and imaging capability without fundamentally changing the overall shell architecture or self-assembly behavior of the microbubbles.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The porphyrin-phospholipid conjugates self-assemble into stable monolayer shells through their inherent amphiphilic properties, without requiring complex external stabilization mechanisms. The conjugated structure inherently provides both structural integrity and imaging functionality, making the system self-sufficient.

Inventive Principle:
Principle #25Self-service

3Adaptability or versatility

If porphyrin-phospholipid conjugate is incorporated into the microbubble shell, then multimodal imaging capability is improved, but manufacturing complexity increases

Engineering Contradiction:
Improvemultimodal imaging capabilityVSAvoidmanufacturing process simplicity
Core Design Contradiction:
Adaptability or versatilityVSEase of manufacture

Solution Approach 1:

The porphyrin-phospholipid conjugates are pre-synthesized with porphyrin attached to the phospholipid side chain before microbubble formation. This preliminary preparation ensures that the imaging capability is built-in from the start, eliminating the need for post-formation modification steps and simplifying the overall manufacturing process despite the complexity of the conjugated structure.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The porphyrin-phospholipid conjugate serves multiple functions simultaneously: it provides structural stability as a shell component, enables fluorescence imaging, photoacoustic imaging, MR imaging, and PET imaging. This multi-functionality is achieved through a single material design, reducing the need for multiple separate components and simplifying manufacturing.

Inventive Principle:
Principle #6Universality (Multi-functionality)

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 porphyrin-phospholipid microbubbles demonstrate improved stability, monodispersity, and enhanced ultrasound and photoacoustic imaging capabilities, with a longer half-life in serum and increased shell stiffness, suitable for various clinical and diagnostic applications.

Implementation Method 1

microbubbles are typically formed from fluorinated gases incorporated into a self-assembled phospholipid shell

Methodology Applied
Scientific EffectSelf-assembly: Self-Assembly

Implementation Method 2

the porphyrin-phospholipid microbubbles demonstrate improved stability, monodispersity, and enhanced ultrasound and photoacoustic imaging capabilities, with a longer half-life in serum and increased shell stiffness

Methodology Applied
Scientific EffectSurface tension: Surface Tension

Implementation Method 3

Microbubbles are gas-filled microspheres which confer acoustic contrast for ultrasound imaging

Methodology Applied
Scientific EffectAcoustic cavitation: Cavitation

Implementation Method 4

Ultrasound is one of the most affordable and accessible imaging modalities

Methodology Applied
Scientific EffectUltrasound: Ultrasound

Implementation Method 5

the porphyrin-phospholipid microbubbles demonstrate improved stability, monodispersity, and enhanced ultrasound and photoacoustic imaging capabilities

Methodology Applied
Scientific EffectPhotoacoustic effect: Photoacoustic Effect

Data Source

PatentEP2766051B1Porphyrin-phospholipid conjugate microbubbles and their use as contrast agents.
Publication Date: 2019.12.04 UNIV HEALTH NETWORK
  • EP2766051B1 patent drawingFigure 1a~1c
  • EP2766051B1 patent drawingFigure 2
  • EP2766051B1 patent drawingFigure 3

AI summary

The present invention relates to a microbubble comprising a monolayer of porphyrin-phospholipid conjugate, said microbubble having encapsulated therein, and to the use of said microbubble in ultrasound imaging of a target area in a subject.