Wikinventia — Atlas of discoveries and inventions · Digital Age

Scalable T-junction mixing method for lipid nanoparticles — Jeffs, MacLachlan et al.

2005 AD · Transmission: Global
BiologyTechnologyMethodNorth American

Lloyd B. Jeffs, Lorne R. Palmer, Ellen G. Ambegia, Cory Giesbrecht, Shannon Ewanick, and Ian MacLachlan (Protiva Biotherapeutics Inc., Burnaby, British Columbia) develop an extrusion-free method for manufacturing lipid nanoparticles: instead of the slow process of forcing liposomes through calibrated membranes (extrusion), they combine a flow of lipids dissolved in ethanol with an aqueous flow of nucleic acid in a T-shaped mixing chamber. Instantaneous dilution of the ethanol below the lipid-solubility threshold generates monodisperse vesicles (under 200 nm) with encapsulation efficiencies above 80%, quickly, reproducibly, and — crucially — scalably to industrial volumes. The original paper encapsulates DNA plasmids, not messenger RNA. However, the T-junction mixing method described here is, according to direct references in later literature on manufacturing mRNA vaccines against COVID-19, the technical basis of the mixing process by which the lipid nanoparticles carrying mRNA in those vaccines are assembled today — later scaled up with microfluidic devices, but preserving the same principle of instantaneous dilution via an ethanol jet.

InstitutionProtiva Biotherapeutics Inc.
Historical regionCanada
Primary sourceJeffs, L.B., Palmer, L.R., Ambegia, E.G., Giesbrecht, C., Ewanick, S., MacLachlan, I. — "A Scalable, Extrusion-Free Method for Efficient Liposomal Encapsulation of Plasmid DNA". Pharmaceutical Research 22(3) (2005), 362–372.
Original languageEnglish
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