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.