Microfluidic Liposome Production via Thin Film Shear Mixing

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Current methods for producing biologically ingestible microemulsion particles or liposomes face challenges such as high energy requirements, environmental hazards from organic solvents, and inefficiencies in achieving uniform particle diameters and high encapsulation ratios, making them unsuitable for industrial-scale production with low environmental impact.

Innovation Solution

A method involving a fluid pressure imparting mechanism and rotation drive mechanism to process fluids through independent pathways between opposing processing surfaces, allowing for the formation of thin film fluids and mixing of components to achieve desired particle sizes with reduced energy input, using pharmacologically acceptable solvents and surfactants, and omitting preliminary mixing steps.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Object-affected harmful factors

If mechanical shearing force methods (high-speed rotating disperser, high-pressure homogenizer) are used to produce microemulsion particles or liposomes, then organic solvents are not used and biologically ingestible materials can be produced, but the energy consumption is large and it is not suitable for high molecules having low resistance to shearing

Engineering Contradiction:
Improveorganic solvent usageVSAvoidenergy consumption
Core Design Contradiction:
Object-affected harmful factorsVSUse of energy by moving object

Solution Approach 1:

The patent replaces traditional mechanical shearing methods (high-speed rotating dispersers, high-pressure homogenizers) with a microfluidic chip-based system that uses controlled fluid flow and pressure differential to generate microemulsion particles. This substitution reduces energy consumption while avoiding the need for high mechanical shear forces that damage sensitive molecules.

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

Solution Approach 2:

The patent transitions from bulk mechanical processing to micro-scale fluidic processing by using a microfluidic chip with specific channel geometries. This dimensional change from macro to micro scale enables particle formation through fluid dynamics rather than mechanical shearing, reducing energy requirements.

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

2Ease of manufacture

If supercritical carbon dioxide is used to produce liposomes in place of organic solvents, then liposomes with intended particle diameter and structure can be produced relatively easily, but pressure ranging from 50-300 atm must be applied

Engineering Contradiction:
Improveease of producing liposomes with intended particle diameterVSAvoidpressure
Core Design Contradiction:
Ease of manufactureVSStress or pressure

Solution Approach 1:

The patent changes the operating parameters from high pressure (50-300 atm supercritical conditions) to ambient or near-ambient pressure by using a microfluidic system with controlled flow rates and pressure differentials. This parameter change maintains ease of manufacture for achieving uniform particle sizes while eliminating the need for extreme pressure conditions.

Inventive Principle:
Principle #35Parameter changes

3Productivity

If high-pressure emulsification is used to produce microemulsion particles, then particles can be produced efficiently, but if pressure is set at high level the base temperature rises upon processing and therefore the stability of emulsion is affected

Engineering Contradiction:
Improveproduction efficiencyVSAvoidbase temperature rise
Core Design Contradiction:
ProductivityVSTemperature

Solution Approach 1:

The patent replaces high-pressure emulsification with a microfluidic mixing system that uses laminar flow and diffusion-based mixing. This substitution eliminates the temperature rise associated with high-pressure processing while maintaining production efficiency through continuous flow operation.

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

Solution Approach 2:

The patent introduces a microfluidic chip as an intermediary device between the input fluids and the final microemulsion product. This intermediary enables controlled mixing and particle formation through its specific channel geometry and flow dynamics, avoiding the need for high-pressure processing that causes temperature rise.

Inventive Principle:
Principle #24Intermediary (Mediator)

4Ease of manufacture

If conventional liposome production methods (Bangham method, organic solvent injection method, reverse phase evaporation method) are used, then liposomes can be produced, but organic solvents harmful to environment and human bodies are used and retention efficiency of water-soluble substances is not high

Engineering Contradiction:
Improveability to produce liposomesVSAvoidenvironmental and human harm from organic solvents
Core Design Contradiction:
Ease of manufactureVSObject-affected harmful factors

Solution Approach 1:

The patent replaces chemical-based methods (organic solvent injection, reverse phase evaporation) with a physical-based microfluidic method. This substitution eliminates harmful organic solvents while maintaining the ability to produce liposomes and microemulsion particles with controlled properties.

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

Solution Approach 2:

The patent extracts and removes the harmful organic solvent component from the production process entirely, replacing it with an aqueous-based microfluidic system. This extraction of the harmful element maintains production capability while eliminating environmental and health hazards.

Inventive Principle:
Principle #2Taking out (Extraction)

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 enables the production of biologically ingestible materials with uniform particle diameters and high encapsulation efficiency while minimizing energy consumption and environmental impact, facilitating safe and efficient industrial-scale production.

Implementation Method 1

A method is provided in which predetermined pressure is applied to a fluid to be processed, two liquids or more including liposome composition components and microemulsion composition components, and aqueous disperse solutions are mixed with each other to obtain a desired biologically ingestible material by uniformly applying shear force thereto

Methodology Applied
Scientific EffectShear force: Shear Stress

Data Source

PatentEP2196194B1Process for producing biological ingesta and biological ingesta obtained thereby
Publication Date: 2017.08.09 M TECH CO LTD
  • EP2196194B1 patent drawingFigure 1(A)~1(D)
  • EP2196194B1 patent drawingFigure 2(A)~2(D)
  • EP2196194B1 patent drawingFigure 3(A)~3(F)

AI summary

The present invention provides a production method for obtaining a biologically ingestible material having an intended diameter with low energy as compared with conventional methods, the method includes mixing a fluid to be processed in a dispersed phase containing a pharmacologically active substance and a fluid to be processed in a continuous phase including at least a disperse solvent, while each of the fluids are retained in an independent state, in a thin film fluid formed between two processing surfaces arranged to be opposite to each other to be able to approach to and separate from each other, at least one of which rotates relative to the other, through independent pathways corresponding to the respective phases, whereby the components contained in the fluid to be processed in a dispersed phase are formed into microparticles having a desired diameter.