A review of confined impinging jet reactor (CIJR) with a perspective of mRNA-LNP vaccine production

In the spotlight of successful breakthrough of the COVID-19 mRNA vaccines, lipid nanoparticles are becoming an important vehicle to deliver a variety of therapeutics. The encapsulation of mRNA using lipids is a self-organizing process that necessitates fast mixing to achieve uniform supersaturation. This is achieved in a confined impinging jet reactor (CIJR) where two input jets collide and fast mix in the mixing chamber. While CIJR is not a new mixing technology, it stands out for its capability to achieve mixing times below a millisecond. This study presents a critical review of major studies concerning CIJRs, starting with the CIJRs' structures and flow characterization, through experimental and numerical studies, and closing with successful applications in a wide range of chemical/pharmaceutical processes. The detailed mixing principles, scaling-up, and mechanisms of making nanoparticles are discussed focusing mainly on the hydrodynamic aspect. The objective of the review is to supply essential information for the optimized design and operation of CIJRs, catering to both industry and academia.