Description
Lipid nanoparticles (LNPs) are a key delivery platform for nucleic acid–based therapeutics, yet early-stage formulation development is often constrained by high material consumption and limited throughput. We present two complementary technologies addressing these challenges: FLIPS, an automated low-volume particle formulation system optimized for screening, and FDmiX, a scalable microfluidic mixing platform for reproducible LNP production.
FLIPS is a single-line, semi-automated encapsulation system designed for formulation volumes in the microliter scale. It employs compressed-air–driven fluid transport, fully reusable fluidic components, and an automated cleaning workflow to minimize cross-contamination and downtime. Integration of a proprietary microfluidic platform and a compact filling station enables formulation volumes below 1 mL, reducing material consumption compared with conventional syringe-pump-based systems. FLIPS is engineered to achieve processing times under 120 s per formulation, and material waste below 30 %, supporting efficient and reproducible screening workflows.
In a proof-of-concept study, LNPs formulated from an ionizable lipid system encapsulating eGFP mRNA were produced at a total flow rate of 25 mL∙min-1. From a total formulation volume of 1 mL, 700 µL of product was recovered. Particle characterization by dynamic light scattering and nanoparticle tracking analysis demonstrated narrow size distributions and low polydispersity (Z-average = 65 nm, PDI = 0.05), comparable to LNPs produced using conventional syringe-pump setups. Encapsulation efficiencies exceeded 95 %, indicating that automation and miniaturization did not compromise formulation performance.
The FDmiX microfluidic mixing platform complements FLIPS by providing highly efficient micromixing across a wide flow range (10–1.000 mL∙min-1). This enables consistent control of critical LNP quality attributes from low-volume screening to high-throughput production, facilitating translation between development stages.
Together, the FLIPS and FDmiX systems constitute an integrated, resource-efficient solution for LNP formulation, enabling rapid screening with minimal material use while maintaining scalability and reproducibility suitable for scale up development.