Full-cycle study on developing a novel structured micromixer and evaluating the nanoparticle products as mRNA...

Area of Science:

• Nanotechnology
• Biomedical Engineering
• Materials Science

Background:

• Precise control of nanoparticle size and uniformity is crucial for effective nanoparticle-based therapies.
• Microfluidic synthesis offers reliability but struggles with mixing efficiency and channel clogging, hindering quality control and scalability.
• Existing methods face challenges in achieving the homogeneity required for therapeutic applications.

Purpose of the Study:

• To develop a novel microfluidic mixer for enhanced nanoparticle synthesis.
• To address limitations of current microfluidic devices, specifically mixing efficiency and operational clogging.
• To produce highly uniform nanoparticles for therapeutic applications with improved quality control.

Main Methods:

• Development of a 3D-printed dual vortex mixer (DVM) with hemispherical baffle microstructures.
• Integration of Dean vortices to create intensified secondary flows for rapid mixing.
• Synthesis and characterization of lipids, liposomes, and polymer nanoparticles, including mRNA-loaded lipid nanoparticles.

Main Results:

• The DVM demonstrated rapid mixing and produced highly uniform nanoparticles (50-130 nm) with a polydispersity index (PDI) below 0.15.
• SARS-CoV-2 Spike mRNA-loaded lipid nanoparticles showed comparable in vitro and in vivo protein expression to a commercial mixer.
• The DVM ensured consistent production without internal clogging during a half-day operation, facilitating quality control and scalability.

Conclusions:

• The novel DVM effectively overcomes microfluidic mixing limitations for nanoparticle synthesis.
• This technology enables scalable, clog-free production of highly uniform nanoparticles for therapeutic applications.
• The DVM offers a promising solution for consistent quality control in nanoparticle manufacturing.