Microfluidic apparatus for producing lipid nanoparticles of various sizes, and manufacturing method using the same

Abstract

The present invention relates to a microfluidic apparatus for producing nucleic acid-deliverable lipid nanoparticles, and a method for producing lipid nanoparticles using the same. Using the microfluidic apparatus, lipid nanoparticles of a desired size can be produced by adjusting the molar ratio between compositions and the Reynolds number.

Claims

[Claim 1] Including inflow channels, mixing channels and outflow channels, The aforementioned inflow channels are two or more, The aforementioned mixed channel includes a micropost, The fluids flowing into different inflow channels are made to flow in different directions. The lipid mixture flows into one inflow channel, and the nucleic acids flow into the other inflow channel. The lipid mixture comprises sterols and further comprises at least one selected from the group consisting of ionized lipids, helper lipids, and PEG-modified lipids. The microposts are arranged in one or more rows in the direction of fluid flow, and in one row, one or more microposts are arranged in a direction different from the direction of fluid flow. The aforementioned plurality of microposts are not arranged in a single line in the direction of fluid flow, but are arranged so as to partially or completely cover the gaps between microposts arranged in adjacent rows when viewed from the direction of fluid flow. The Reynolds number for the fluid flow in the mixing channel is 25 to 100. A microfluidic apparatus for producing lipid nanoparticles, wherein the molar ratio of sterols to the lipid mixture is 0.3 to 0.

86. [Claim 2] The microfluidic apparatus for producing lipid nanoparticles according to claim 1, characterized in that the lipid mixture flows in in the same direction as the fluid flow, and the nucleic acids flow in in a direction different from the fluid flow. [Claim 3] The microfluidic apparatus for producing lipid nanoparticles according to claim 2, characterized in that the lipid mixture flows in in the same direction as the fluid flow, and the nucleic acids flow in in a direction perpendicular to the fluid flow. [Claim 4] The microfluidic apparatus for producing lipid nanoparticles according to claim 1, characterized in that the microposts are connected to or not connected to the walls constituting the mixing channel. [Claim 5] The microfluidic apparatus for producing lipid nanoparticles according to claim 1, characterized in that the size of the lipid nanoparticles is adjusted by the molar ratio of the lipid mixture to the sterol.

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