Microfluidic and Turbulent Mixing for mRNA LNP Vaccines.

Abstract

Using lipid nanocarriers to deliver the mRNA of a specific antigen to immune cells is a powerful innovative approach to rapidly develop new safe and effective vaccines. Understanding and optimizing the mixing process necessary for mRNA lipid nanoparticles (LNPs) is the focus of this review. The first objective is to review the fundamentals of microfluidic and turbulent fluid-mixing basics needed to understand the mixing process. The mRNA LNP self-assembly flash nanoprecipitation/self-assembly process will be discussed. Then, some important experimental nanoparticle studies which are the basis for the current understanding of microfluidic and turbulent mRNA LNP mixing process will be reviewed. Finally, the current commercially available LNP mixing technology will be summarized. There appears to be no universally "best" mixing process for formulating nanoparticles or mRNA LNPs. Both chaotic advection and turbulent flow microfluidic mixing devices, using the proper parameters for each device, will formulate similar mRNA LNP vaccines during development research. However, the low fluid output of microfluidic devices may not be practicable at higher fluid flow rates. Larger-scale turbulent mixing devices are more suitable for clinical-scale mRNA LNP production.