Lipid nanoparticles (LNPs) have become major delivery vehicles for RNA and other polynucleotides. Yet their manufacturing and storage still rely heavily on empirical approaches: their structure emerges within milliseconds during mixing, but may also reorganise when the continuous phase is changed, and may continue to evolve as the formulation is concentrated. Better control of these trajectories is essential to obtain robust and reproducible LNPs.

The PROSALIDE project combines microfluidics, soft-matter physical chemistry and structural characterisation to connect formulation conditions, structure and metastability. The Colloids and Complex Fluids team at the Laboratoire de Génie Chimique in Toulouse conducts the project, funded by the French National Research Agency (ANR) since 2023.

Over the past three years, the team has developed tools to rapidly mix the fluids used to form LNPs, characterise their structures using X-ray and neutron scattering, and investigate the drying of model and real fluids in confined geometries. The position builds on these advances and will address two specific challenges: (1) implementing multi-stage synthesis strategies and (2) systematically studying particle compression by drying.

(1) The team already has functional microfluidic chips for the rapid mixing required to produce LNPs. The successful candidate will learn their fabrication method and experimental operation, contribute to further optimisation, and support the formulation experiments currently conducted in the laboratory in collaboration with the PhD students involved in the project. More specifically, the work will focus on developing multi-stage mixing architectures to explore new LNP formation conditions. Structural characterisation by light, X-ray and neutron scattering will be carried out, partly at large-scale research facilities.

(2) The team has developped microfluidic drying cells that can be used to concentrate colloid systems, such as LNP dispersions. The objective will be to investigate changes in LNP structure and metastability during compression, including at high concentrations and in the presence of other solutes. These experiments will provide insight into LNP behaviour under conditions relevant to storage. Monitoring will rely primarily on Raman spectroscopy, complemented by scattering techniques.