Temperature-Controlled Microparticle Formation via Microfluidic Cooling

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Solution Overview

Problem

Conventional methods for preparing size-controlled microparticles, such as gas-filled microvesicles, face challenges in maintaining monodispersity due to high kinetic energy collisions at high flow rates, leading to coalescence and uncontrollable size distribution.

Innovation Solution

The method involves controlling the temperature of the microparticles by maintaining the initial portion of the outlet channel at a temperature at least 20% lower than the transition temperature of the amphiphilic material and subsequent rapid cooling below the transition temperature to reduce coalescence and maintain desired size and polydispersity index.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If high flow rates are used in flow-focusing devices to achieve high formation rates, then productivity is improved, but coalescence occurs due to high kinetic energy collisions leading to loss of manufacturing precision

Engineering Contradiction:
Improveformation rateVSAvoidsize control
Core Design Contradiction:
ProductivityVSManufacturing precision

Solution Approach 1:

The patent changes the temperature parameter of the continuous phase to match or exceed the transition temperature of the amphiphilic material. This parameter change reduces the surface mobility of the stabilizing layer, thereby reducing coalescence between microparticles even at high flow rates, allowing high productivity while maintaining size control

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent applies preliminary heating to the continuous phase before the microparticles are formed, ensuring that the temperature is already at or above the transition temperature of the amphiphilic material when the microparticles are being formed. This preliminary action prevents coalescence from occurring in the first place during the high-speed formation process

Inventive Principle:
Principle #10Preliminary action

2Ease of manufacture

If conventional emulsification methods are used to prepare microparticles, then ease of manufacture is improved, but polydispersity is high leading to poor manufacturing precision

Engineering Contradiction:
Improvepreparation simplicityVSAvoidsize uniformity
Core Design Contradiction:
Ease of manufactureVSManufacturing precision

Solution Approach 1:

The patent replaces conventional mechanical emulsification methods with a flow-focusing microfluidic system. This substitution uses controlled fluid dynamics and surface tension effects at the orifice to generate monodisperse microparticles, achieving high manufacturing precision while maintaining ease of manufacture through automated flow control

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent transitions from bulk emulsification to microfluidic flow focusing, effectively moving the process to a different dimensional regime. The confinement of flows in micro-scale channels creates precisely controlled collision and breakup dynamics that generate uniform microparticles, solving the polydispersity problem while keeping the process simple

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

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 reduces coalescence, achieving a polydispersity index of less than 10%, preferably less than 5%, and even further minimizes coalescence to less than 1%, ensuring controlled size and stability of the microparticles.

Implementation Method 1

aqueous suspensions of gas-filled microvesicles where the bubbles of gas are bounded, at the gas/liquid interface, by a very thin envelope (film) involving a stabilizing amphiphilic material (typically a phospholipid) disposed at the gas to liquid interface

Methodology Applied
Scientific EffectAmphiphilic material stabilization: Amphiphiles

Implementation Method 2

a flow of a first fluid component (e.g. a gas or an oil) is focused by a flow of a second fluid component through a narrow orifice

Methodology Applied
Scientific EffectFlow focusing: Focusing

Implementation Method 3

Ref. 7 investigates the gas jet breakup and the resulting microbubble formation in a microfluidic flow focusing device

Methodology Applied
Scientific EffectGas jet breakup: Jet

Implementation Method 4

an initial portion of said outlet channel is kept at a temperature (°C) of not less than 20% lower with respect to the transition temperature of the amphiphilic material

Methodology Applied
Scientific EffectTemperature control: Temperature Gradient

Implementation Method 5

The Applicant has now found suitable preparation conditions which may be applied for limiting the coalescence of the microparticles prepared according to microfluidic methods

Methodology Applied
Scientific EffectCoalescence reduction: Cohesion

Data Source

PatentEP3506882B1Preparation of size-controlled microparticles
Publication Date: 2022.01.12 BRACCO SUISSE SA
  • EP3506882B1 patent drawingFigure 1
  • EP3506882B1 patent drawingFigure 2~3
  • EP3506882B1 patent drawingFigure 4a~4e

AI summary

A method for preparing a suspension of size-controlled microparticles stabilized by a layer of amphiphilic material. The method, which may be applied to preparations using microfluidic techniques, comprises controlling the temperature of the microparticles during the preparation process and preferably while collecting the formed microparticles.