Gravity-Based mRNA Liposome Encapsulation Without Pumps

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Current methods for producing mRNA-loaded lipid nanoparticles suffer from poor encapsulation efficiency, low mRNA recovery, and require specialized equipment, which may not be readily available in all settings.

Innovation Solution

A gravity-based mixing process for lipid nanoparticle formulation and mRNA encapsulation, which eliminates the need for pumps and provides a cost-effective, robust, and user-friendly method for encapsulating mRNA in liposomes with improved efficiency and flexibility.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If specialized equipment such as gear pumps or peristaltic pumps is used for mRNA encapsulation, then encapsulation process can be performed, but equipment complexity increases and availability decreases

Engineering Contradiction:
Improveencapsulation process availabilityVSAvoidequipment complexity
Core Design Contradiction:
Ease of manufactureVSDevice complexity

Solution Approach 1:

The patent removes the pump component from the encapsulation system entirely, extracting the active mixing function and replacing it with a passive gravity-driven flow system. This eliminates the need for complex mechanical equipment while maintaining the encapsulation process capability.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The system uses the natural properties of the solutions themselves (density differences, gravity) to drive the flow and mixing processes. The mRNA solution and lipid solution automatically flow and mix without external mechanical assistance, making the system self-sufficient and equipment-free.

Inventive Principle:
Principle #25Self-service

2Productivity

If pump-based mixing is used for lipid nanoparticle formulation, then flow control is achieved, but mRNA recovery decreases and encapsulation efficiency is poor

Engineering Contradiction:
ImprovemRNA recovery rateVSAvoidencapsulation efficiency
Core Design Contradiction:
ProductivityVSManufacturing precision

Solution Approach 1:

The system employs periodic or pulsatile flow patterns that occur naturally during gravity-driven mixing, creating optimal conditions for mRNA encapsulation at specific moments in the mixing cycle. This periodic action enhances both recovery and efficiency without requiring mechanical control.

Inventive Principle:
Principle #19Periodic action

Solution Approach 2:

The patent optimizes physical parameters such as flow rates, mixing ratios, and gravitational forces to achieve superior encapsulation efficiency and mRNA recovery. By carefully controlling these parameters in the gravity-based system, the process outperforms pump-based methods.

Inventive Principle:
Principle #35Parameter changes

3Ease of operation

If pump-based systems are used for encapsulation, then flow rates can be controlled, but cost increases and maintenance requirements increase

Engineering Contradiction:
Improveflow rate controlVSAvoidcost efficiency
Core Design Contradiction:
Ease of operationVSEase of manufacture

Solution Approach 1:

The patent replaces the mechanical pump-based flow control system with a gravity-based passive flow system. Flow rates are controlled by gravitational force and system geometry rather than mechanical actuators, eliminating costs associated with pumps, power supply, and maintenance while maintaining operational control.

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

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 process achieves high encapsulation efficiencies and mRNA recovery rates, is scalable, and does not require specialized equipment, making it suitable for various settings, including patient-care settings.

Implementation Method 1

a gravity-based mixing process for lipid nanoparticle formulation and mRNA encapsulation

Methodology Applied
Scientific EffectGravity: Gravitation

Data Source

PatentUS20210378962A1Pumpless encapsulation of messenger RNA
Publication Date: 2021.12.09 TRANSLATE BIO INC
  • US20210378962A1 patent drawing
  • US20210378962A1 patent drawing
  • US20210378962A1 patent drawing

AI summary

The present invention provides, among other things, a process of encapsulating messenger RNA (mRNA) in liposomes comprising a. providing a first stream comprising an mRNA solution at a first controlled flow rate, b. providing a second stream comprising a lipid solution at a second controlled flow rate, and c. mixing the first stream and the second stream to form mRNA-encapsulated liposomes, wherein the first controlled flow rate and the second controlled flow rate are achieved without use of a pump.