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Mass production system for RNA-loaded lipid nanoparticles using piling up microfluidic devices

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Title: Mass production system for RNA-loaded lipid nanoparticles using piling up microfluidic devices
Authors: Maeki, Masatoshi Browse this author
Okada, Yuto Browse this author
Uno, Shuya Browse this author
Sugiura, Kaisei Browse this author
Suzuki, Yuichi Browse this author
Okuda, Kento Browse this author
Sato, Yusuke Browse this author →KAKEN DB
Ando, Masao Browse this author
Yamazaki, Hiroyuki Browse this author
Takeuchi, Masaki Browse this author
Ishida, Akihiko Browse this author →KAKEN DB
Tani, Hirofumi Browse this author →KAKEN DB
Harashima, Hideyoshi Browse this author →KAKEN DB
Tokeshi, Manabu Browse this author →KAKEN DB
Keywords: Lipid nanoparticles
mRNA vaccines
Microfluidic device
Mass production
Issue Date: Apr-2023
Publisher: Elsevier
Journal Title: Applied materials today
Volume: 31
Start Page: 101754
Publisher DOI: 10.1016/j.apmt.2023.101754
Abstract: Microfluidic devices are widely used in lipid nanoparticle (LNP)-based vaccines and nanomedicine research. These devices should be stiff enough to withstand the high flow rate for the mass production of LNPs, and malleable enough to use when fabricating complicated microchannel or micromixer structures, such as stag-gering herringbone micromixers. Due to the limitations of the available fabrication methods, optimal micro -fluidic devices have not yet been developed. In this study, we report the development of a glass-based microfluidic device based on the invasive Lipid Nanoparticle Production (iLiNP) device (R) reported previously. The LNP size controllability of glass-based iLiNP device was similar to that of the poly(dimethylsiloxane) (PDMS)-based iLiNP device, and the glass-iLiNP device was used for mRNA-loaded LNP production with ionizable lipids used for COVID-19 mRNA vaccines. We also demonstrate a piling-and numbering-up strategy based on glass-iLiNP device. The iLiNP unit composed of five-layered microchannels was fabricated by piling-up each glass-iLiNP device followed by parallelization (numbering-up) for the mass production of LNPs. This iLiNP system can produce LNPs with sizes ranging between 20 and 60 nm at a flow rate of 20-50 mL/min, and its performance is comparable to that of the commercially available microfluidic system like NanoAssemblr (R).
Type: article
Appears in Collections:工学院・工学研究院 (Graduate School of Engineering / Faculty of Engineering) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

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