Multiport Valve Priming for Lipid Nanoparticle and Liposome Manufacturing
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Solution Overview
Problem
Existing manufacturing systems for lipid nanoparticles and liposomes face issues with particle size control, clogging of extrusion membranes, and inefficiencies in priming and equilibrating mixing assemblies, leading to material and time wastage during the initiation of the manufacturing process.
Innovation Solution
A system incorporating a multiport switching valve between pumps and a mixing device allows for priming of fluid lines without loss of stock solution, enabling instantaneous switching to mixing mode with precise component proportions and conditions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If continuous addition of both components in fixed proportion is used (in-line mixing), then particle size control is improved, but significant material is discarded during priming of the system
Solution Approach 1:
The system performs preliminary priming action using only the aqueous phase through the mixing chamber before introducing the organic phase. This preliminary action conditions the mixing chamber and flow paths without wasting the valuable organic component, thereby maintaining particle size control precision while reducing material loss during system priming.
2Quantity of substance
If slow addition of one component to another under rapid mixing conditions is used, then particle formation occurs, but the composition of the mixture continually changes during addition
Solution Approach 1:
The system replaces the mechanical addition process with a valve-controlled flow distribution mechanism. The switching valve automatically maintains fixed proportions of organic and aqueous phases by controlling their respective flow paths, eliminating the composition variability inherent in manual or mechanical addition methods while ensuring consistent particle formation.
Solution Approach 2:
The system employs flow sensors and control logic that monitor the actual flow rates of both phases and dynamically adjust the switching valve positions to maintain the target flow ratio. This feedback mechanism ensures that mixture composition remains stable and consistent throughout the manufacturing process, producing uniform particles.
3Manufacturing precision
If extrusion through membranes with well-defined pore sizes is used to reduce particle size, then particle size control is achieved, but clogging of extrusion membranes occurs
Solution Approach 1:
The system extracts and eliminates the extrusion membrane component from the manufacturing process. By using valve-controlled direct mixing of organic and aqueous phases, the system achieves particle size control without requiring membrane extrusion, thereby completely avoiding the clogging problem associated with membranes while maintaining manufacturing precision.
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
Reduces material and time wastage during priming, ensuring consistent particle formation by maintaining target proportions and mixing conditions, enhancing the efficiency of lipid nanoparticle production.
Implementation Method 1
the valve has a first operating position in which the first valve inlet port is fluidically coupled to the first valve outlet port and the second valve inlet port is fluidically coupled to the second valve outlet port and a second operating position in which the first valve inlet port is not fluidically coupled to the first valve outlet port and the second valve inlet port is not fluidically coupled to the second valve outlet port
Implementation Method 2
flowing the organic lipid stock solution through the valve to the first mixing assembly inlet of a mixing assembly and flowing the aqueous nucleic acid stock solution through the valve to the second mixing assembly inlet of a mixing assembly thereby mixing the organic lipid stock solution and the aqueous nucleic acid stock solution within the mixing assembly
Data Source
Figure 1
Figure 2
Figure 3~4B
AI summary
Systems including specific arrangements of pumps, valves, and conduits, such as for mixing precursors to lipid nanoparticles to form the lipid nanoparticles, are provided. Methods of using such systems to manufacture the lipid nanoparticles are also provided.