Fluidic mixer unit device for nanoparticle production

A computer-implemented method of manufacturing a device, the method being implemented by at least one processor executing software instructions, the device including a microplate having a plurality of fluidic mixing units arranged in an array, each fluidic mixing unit defining a flowpath with each flowpath having a plurality of fluid inlet channels with each fluid inlet channel including an inlet such that, collectively, the inlets of the plurality of fluid inlet channels define a plurality of inlets of the fluidic mixing unit, and a mixing channel including an outlet that defines a single outlet of the fluidic mixing unit, wherein, along the flowpath, the plurality of fluid inlet channels converge downstream into the mixing channel, and wherein each fluidic mixing unit of the plurality of fluidic mixing units is configured to produce nanoparticles, the method comprising:

• creating, by the at least one processor, a first fluidic mixing unit object having a first configuration of the flowpath;
• creating, by the at least one processor, a second fluidic mixing unit object having a second configuration of the flowpath, the first configuration being different from the second configuration;
• assembling, by the at least one processor, at least a first set of a plurality of the first fluidic mixing unit objects and a second set of a plurality of the second fluidic mixing unit objects into an array object;
• and
• 3D printing the device using the array object.

A method for producing lipid nanoparticles with a device, the device including a microplate having a plurality of fluidic mixing units arranged in an array, each fluidic mixing unit defining a flowpath with each flowpath having a plurality of fluid inlet channels with each fluid inlet channel including an inlet such that, collectively, the inlets of the plurality of fluid inlet channels define a plurality of inlets of the fluidic mixing unit, and a mixing channel including an outlet that defines a single outlet of the fluidic mixing unit, wherein, along the flowpath, the plurality of fluid inlet channels converge downstream into the mixing channel, and wherein each fluidic mixing unit of the plurality of fluidic mixing units is configured to produce nanoparticles, the method comprising:

• injecting a lipid solution into a first inlet of the plurality of inlets of each fluidic mixing unit;
• injecting an mRNA solution into a second inlet and a third inlet of the plurality of inlets of each fluidic mixing unit;
• and
• mixing the lipid solution and the mRNA solution within the mixing channel of each fluidic mixing unit for a time sufficient to form lipid nanoparticles, wherein after mixing, the lipid nanoparticles formed exits the single outlet of each fluidic mixing unit.

A method of evaluating lipid nanoparticle production with a device, the device including a microplate having a plurality of fluidic mixing units arranged in an array, each fluidic mixing unit defining a flowpath with each flowpath having a plurality of fluid inlet channels with each fluid inlet channel including an inlet such that, collectively, the inlets of the plurality of fluid inlet channels define a plurality of inlets of the fluidic mixing unit, and a mixing channel including an outlet that defines a single outlet of the fluidic mixing unit, wherein, along the flowpath, the plurality of fluid inlet channels converge downstream into the mixing channel, and wherein the array of the plurality of fluidic mixing units includes at least a first set of fluidic mixing units having a first configuration of the flowpath, and a second set of fluidic mixing units having a second configuration of the flowpath, wherein the first configuration is different from the second configuration, and wherein each fluidic mixing unit of the plurality of fluidic mixing units is configured to produce nanoparticles, the method comprising:

• injecting a first lipid solution into a first inlet and mRNA into a second inlet and a third inlet of each fluidic mixing unit of the first set of fluidic mixing units;
• injecting a second lipid solution into a first inlet and mRNA into a second inlet and a third inlet of each fluidic mixing unit of the second set of fluidic mixing units;
• mixing the first lipid solution and mRNA within the mixing channel of each fluidic mixing unit of the first set of fluidic mixing units for a time sufficient to form lipid nanoparticles, wherein after mixing, the lipid nanoparticles formed exits the device through the single outlet of each fluidic mixing unit;
• mixing the second lipid solution and mRNA within the mixing channel of each fluidic mixing unit of the second set of fluidic mixing units for a time sufficient to form lipid nanoparticles, wherein after mixing, the lipid nanoparticles formed exits the device through the single outlet of each fluidic mixing unit;
• evaluating nanoparticles formed from the first set of fluidic mixing units;
• and
• evaluating nanoparticles formed from the second set of fluidic mixing units.

A method of evaluating lipid nanoparticle production with a device, the device including a microplate having a plurality of fluidic mixing units arranged in an array, each fluidic mixing unit defining a flowpath with each flowpath having a plurality of fluid inlet channels with each fluid inlet channel including an inlet such that, collectively, the inlets of the plurality of fluid inlet channels define a plurality of inlets of the fluidic mixing unit, and a mixing channel including an outlet that defines a single outlet of the fluidic mixing unit, wherein, along the flowpath, the plurality of fluid inlet channels converge downstream into the mixing channel, and wherein the array of the plurality of fluidic mixing units includes at least a first set of fluidic mixing units and a second set of fluidic mixing units, and wherein each fluidic mixing unit of the plurality of fluidic mixing units is configured to produce nanoparticles, the method comprising:

• injecting a first lipid solution into a first inlet and mRNA into a second inlet and a third inlet of each fluidic mixing unit of the first set of fluidic mixing units;
• injecting a second lipid solution into a first inlet and mRNA into a second inlet and a third inlet of each fluidic mixing unit of the second set of fluidic mixing units, wherein the first lipid solution is different from the second lipid solution;
• mixing the first lipid solution and the mRNA within the mixing channel of each fluidic mixing unit of the first set of fluidic mixing units for a time sufficient to form lipid nanoparticles, wherein after mixing, the lipid nanoparticles formed exits the device through the single outlet of each fluidic mixing unit;
• mixing the second lipid solution and the mRNA within the mixing channel of each fluidic mixing unit of the second set of fluidic mixing units for a time sufficient to form lipid nanoparticles, wherein after mixing, the lipid nanoparticles formed exits the device through the single outlet of each fluidic mixing unit;
• evaluating nanoparticles formed from the first set of fluidic mixing units;
• and
• evaluating nanoparticles formed from the second set of fluidic mixing units.