Accessible materials characterization of lipid nanoparticles for nucleic acid delivery

Nucleic acids can revolutionize human health outcomes, as evidenced by mRNA lipid nanoparticle (LNP) vaccines used to combat COVID-19. Despite the success of these non-viral delivery vectors, their physicochemical properties are not well understood, making them difficult to tune and optimize. However, the materials and methods used for their production are expensive, making fundamental studies on them cost prohibitive for many researchers. In this work, we leverage high-throughput methods to prepare a variety of LNP formulations and analyze their structural properties. Our techniques combine open-source liquid handling robots with analysis techniques using well plates such as plate reader fluorescence and UV/Vis assays, as well as small-angle x-ray scattering (SAXS). This platform allows the synthesis and material characterization of a breadth of conditions with minimal reagent volumes, creating an accessible and largely autonomous workflow for fundamental LNP research.