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

Herein, a high‐throughput microfluidic platform is presented that addresses the challenges in lipid nanoparticles (LNPs) formulation screening and scale‐up through the design of micromixers with unique aerofoil structures. These structures are optimized to enhance mixing and LNP formation across a wide flow rate range (0.2–50 mL min −1 ), using minimal reagent volumes (as low as 0.1 mL) up to liter‐scale production. A high‐throughput formulation screening instrument named MiNANO‐form and a microfluidic cartridge with eight parallel channels is introduced, which enables simultaneous synthesis of multiple LNP formulations with excellent quality (size 38–150 nm and polydispersity index (PDI), PDI < 0.2) and reproducibility. In addition, for a seamless scale‐up, the platform consists of a custom‐made modular microfluidic unit, named MiNANO‐scale, capable of continuous LNP production at up to 50 mL min −1 . The platform's performance is validated through mRNA and pDNA transfection, as well as siRNA uptake studies in HEK293, A549, and CFBE cells.