Optimal Self-assembly of Lipid Nanoparticles (LNP) in a Ring Micromixer

This is the authors' abstract. We don't add key points for this paper.

Lipid nanoparticles (LNPs) for RNA and DNA delivery have gained considerable attention to treat a broad range of diseases and to vectorize mRNA for COVID vaccines. LNPs are produced by mixing biomolecules and lipids, which self-assemble to form the desired structure. In this domain, microfluidics shows clear advantages: high mixing quality under low stress conditions added to fast preparation. Studies of LNPs produced in micromixers have revealed, in certain ranges of flow-rates, a degradation of performances in terms of size, size monodispersivity and encapsulation efficiency. In this study we focus on the ring micromixer, well adapted to high throughputs. We reveal three regimes - side-by-side, transitionnal and highly mixed – which control the mixing performance of the device. Further, on using cryo-TEM and biochemical analysis, we show that the mixing performances are strongly correlated to the characteristics of the LNPs we produce. We underline the important role of the flow-rate ratio and propose a physical criterion, based on the onset of temporal instabilities, coupled to a stochiometric one, for producing LNPs with optimal characteristics, in term of geometry, monodispersivity and encapsulation yield. These criteria are general.