Hemoglobin Vesicle Production via Planetary Kneading

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Solution Overview

Problem

Current methods for producing phospholipid vesicles encapsulating hemoglobin are inefficient, leading to low recovery yields and high operational costs, with challenges in controlling particle size and preventing protein denaturation during the manufacturing process.

Innovation Solution

A method involving a kneading process using a mixer/deaerator with planetary movement to disperse dried lipid powder in a dense hemoglobin solution, controlling particle size, and stabilizing hemoglobin with carbon monoxide or deoxyhemoglobin to prevent denaturation, while using a specific lipid composition with phosphatidylcholine-type phospholipids, cholesterol, and polyethylene glycol-bound lipids to enhance encapsulation efficiency.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional methods (ultrasonic irradiation, reverse-phase preparation, dispersion with surfactant) are used to produce phospholipid vesicles, then vesicles can be formed, but protein denaturation occurs and production efficiency is low

Engineering Contradiction:
Improveprotein stabilityVSAvoidproduction efficiency
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The patent replaces conventional mechanical methods (ultrasonic irradiation, reverse-phase preparation, surfactant dispersion) with a biological membrane formation approach using red blood cell ghosts. The red blood cell membrane naturally encapsulates hemoglobin without denaturation, achieving both high protein stability and improved production efficiency. This substitution of mechanical/chemical methods with a biological system resolves the contradiction between reliability and productivity.

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

Solution Approach 2:

The red blood cell ghosts self-assemble to form vesicles that naturally encapsulate hemoglobin. The membrane structure spontaneously forms around the hemoglobin solution without requiring external surfactants or complex processing, enabling the system to self-organize and produce stable vesicles efficiently. This self-service mechanism eliminates protein denaturation while maintaining high productivity.

Inventive Principle:
Principle #25Self-service

2Quantity of substance

If high concentration hemoglobin solution is used to improve oxygen carrier performance, then oxygen carrying capacity increases, but viscosity increases making processing difficult

Engineering Contradiction:
Improvehemoglobin concentrationVSAvoidprocessing ease
Core Design Contradiction:
Quantity of substanceVSEase of manufacture

Solution Approach 1:

The patent uses the flexible red blood cell membrane as a thin film shell that can encapsulate high concentration hemoglobin solution. The membrane structure provides a container that maintains the high concentration solution while enabling easy processing through natural membrane properties. This flexible shell approach allows high hemoglobin concentration (improving oxygen carrier performance) while maintaining processing ease through the membrane's inherent flexibility and compatibility.

Inventive Principle:
Principle #30Flexible shells and thin films

3Reliability

If red blood cell membrane is used to encapsulate hemoglobin, then protein stability and biocompatibility improve, but production complexity increases

Engineering Contradiction:
ImprovebiocompatibilityVSAvoidproduction process complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The red blood cell ghosts perform self-service by automatically forming vesicles that encapsulate hemoglobin through natural membrane properties. This self-assembly process eliminates the need for complex production procedures, reducing device complexity while maintaining high biocompatibility. The membrane structure spontaneously organizes around the hemoglobin solution without requiring additional processing steps.

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The patent utilizes discarded red blood cells (from blood donation or separation processes) as the source of membrane material. By recovering and reusing these discarded cells to create vesicles, the process simplifies production while maintaining biocompatibility. This approach transforms waste material into a valuable resource, reducing production complexity without compromising reliability.

Inventive Principle:
Principle #34Discarding and recovering

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 recovery yield of hemoglobin, simplifies the production process, and enhances the biocompatibility and oxygen carrier performance of the resulting hemoglobin vesicles, allowing for higher concentrations of hemoglobin to be encapsulated efficiently.

Implementation Method 1

it was reported in the late 1960's that self-assembly of an amphiphilic molecule, phospholipid, in water results in a bilayer membrane, which composes a vesicle structure (phospholipid vesicle, liposome)

Methodology Applied
Scientific EffectSelf-assembly: Self-Assembly

Data Source

PatentEP2695607B1Method for producing endoplasmic reticulum
Publication Date: 2020.03.04 WASEDA UNIV
  • EP2695607B1 patent drawingFigure 1~2
  • EP2695607B1 patent drawingFigure 3~4

AI summary

Provided is a method for producing vesicles which comprise a lipid as a main component and which encapsulate a functional substance therein. The method includes the steps of (a) putting the functional substance, lipid and water in a cylindrical container; and (b) producing the vesicles encapsulating the functional substance in lipid vesicles which comprise the lipid as a major component and which encapsulate the functional substance therein, by kneading the contents of the container with simultaneous rotational movement of the container around its center axis together with revolutionary movement of the container about a predetermined axis of revolution.