Unique Aerofoil-Structured Microfluidics for High Throughput Lipid Nanoparticle Formulation Screening and Scale-up

Area of Science:

• Biotechnology and Biomedical Engineering
• Nanotechnology
• Chemical Engineering

Background:

• Lipid nanoparticles (LNPs) are crucial for nucleic acid delivery but face challenges in formulation screening and scale-up.
• Existing methods often require large reagent volumes and lack high-throughput capabilities.

Purpose of the Study:

• To develop a high-throughput microfluidic platform for efficient LNP formulation screening and seamless scale-up.
• To address limitations in mixing efficiency and LNP quality control during LNP production.

Main Methods:

• Design of micromixers with aerofoil structures for enhanced mixing across a wide flow rate range (0.2-50 mL min⁻¹).
• Development of a high-throughput screening instrument (MiNANO-form) with parallel microfluidic channels.
• Implementation of a modular microfluidic unit (MiNANO-scale) for continuous, scalable LNP production.

Main Results:

• Achieved consistent LNP formation with sizes ranging from 38-150 nm and polydispersity index (PDI) < 0.2.
• Demonstrated high-throughput screening using minimal reagent volumes (as low as 0.1 mL).
• Validated scalable production up to liter-scale (50 mL min⁻¹) and successful transfection/uptake studies in various cell lines.

Conclusions:

• The developed microfluidic platform enables rapid optimization and scalable manufacturing of high-quality lipid nanoparticles.
• This technology significantly advances LNP formulation and production for therapeutic applications.
• The platform's versatility is confirmed by successful mRNA, pDNA, and siRNA delivery studies.