Gas Microbubble Preparation via Preheated Protein and Shear Mixing
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Solution Overview
Problem
Existing processes for preparing ultrasound contrast media with gas microbubbles encapsulated by proteins result in a broad size distribution and variable yield, making it difficult to achieve reproducible microbubbles with a narrow size distribution.
Innovation Solution
A process involving the preheating of both the protein solution and gas before mixing, using high shear forces to form microbubbles, which ensures a stable temperature and uniform mixing, thereby achieving a narrow size distribution and improved yield.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If conventional mixing processes are used to prepare gas microbubbles, then the process is simple, but the microbubbles have a broad size distribution and variable yield
Solution Approach 1:
The protein solution is preheated to the denaturation temperature before mixing with the gas. This preliminary thermal treatment ensures that the protein is in the correct state for encapsulation, leading to consistent microbubble formation and narrow size distribution without requiring complex post-processing controls
Solution Approach 2:
The process controls the temperature parameter of the protein solution, heating it to a specific denaturation temperature range before mixing. This parameter change transforms the protein structure to enable proper encapsulation at the gas-liquid interface, resulting in reproducible microbubble sizes
2Productivity
If shaking or sonication is used to produce microbubbles, then the process is straightforward, but the yield varies from batch to batch
Solution Approach 1:
The process changes the temperature parameter of the protein solution to the denaturation temperature, which fundamentally alters the protein's physical state and encapsulation behavior. This standardized parameter change ensures consistent yield and reliability across batches by controlling the protein's interaction with the gas interface
Solution Approach 2:
The invention replaces mechanical mixing methods (shaking, sonication) with a controlled thermal processing approach. By using heat to denature the protein before mixing, the process achieves more reliable and reproducible encapsulation compared to variable mechanical energy input methods
3Manufacturing precision
If a robust process is implemented to achieve narrow size distribution, then the manufacturing precision improves, but the process complexity increases
Solution Approach 1:
Heating the protein solution to denaturation temperature before mixing is a preliminary action that simplifies the overall process. This single pre-treatment step ensures proper protein conformation for encapsulation, achieving narrow size distribution without requiring multiple complex process controls or adjustments
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 process consistently produces microbubbles with a narrow size distribution and low standard deviation, meeting product specifications and reducing material loss, making it economically viable.
Implementation Method 1
an aqueous solution of a heat-denaturable protein is combined with a gas, and these are mixed mechanically using high shear forces. Surprisingly it has been found that before mixing the protein and the gas, both the protein and the gas should be heated, providing a robust process wherein the generated microbubbles have a narrow size distribution.
Implementation Method 2
dispersing the gas into the protein solution by subjecting the gas/liquid mixture to mechanical shear forces to form a composition of gas microbubbles encapsulated by denatured protein
Data Source
AI summary
A process for preparing a composition comprising encapsulated gas microbubbles, the process comprising: providing an aqueous protein solution of a heat-denaturable protein at a temperature necessary to achieve incipient denaturation; heating a gas by using heat from the heated protein solution; mixing the heated gas and the heated protein solution to obtain a gas/liquid mixture; and dispersing the gas into the protein solution by subjecting the gas/liquid mixture to mechanical shear forces to form a composition of gas microbubbles encapsulated by denatured protein.