Understanding the influence microfluidic reactor geometry on mRNA lipid nanoparticle assembly using in situ neutron scattering

The assembly of lipid nanoparticles is critical for the successful delivery of messenger RNA therapies, enabling the treatment of previously undruggable diseases and enhancing immunization against emerging pathogens. These nanoparticles are essential due to their role in protecting the mRNA and facilitating efficient delivery to target tissues and cells after administration. To enable scale up friendly discovery of LNPs formulations, these nanoparticles are typically fabricated using microfluidic mixing due to the high mixing dependency of the flash precipitation process. We recently conducted a first-in-class experiment to measure how LNP structure evolves during fabrication in situ via SANS directly on a microfluidic chip. As microfluidic assembly of LNPs is dependent on mixing properties, we now wish to further explore this space by evaluating the effect of mixing junction geometry on the evolution on LNP structure. We will evaluate geometries such as cross mixers, T-junctions, micromixers and staggered herringbone which are well established in the LNP field yielding information which will be impactful across the research field. The experiment will be supported by molecular dynamics simulations to aid with fitting, as well as advanced characterisation of the micro- and macro-mixing properties of the reactor designs. The outcomes of this experiment will support further development of new microfluidic chip and provide new insights into the LNP manufacturing processes.