Microfluidic Mixing

Make high quality lipid nanoparticles

Bring it all together

Lipid nanoparticles (LNPs) can be made in a wide range of sizes and are made up of an outer layer of lipids and an inner core that carries a payload. These three main characteristics of the LNP affect its functionality. The lipids selected must be solubilized in an organic solute, usually ethanol - your organic formulation. The payload, which can be mRNA, siRNA, proteins, etc., is prepared in an aqueous buffer — your aqueous formulation. Once you’ve chosen all your LNP parts, it’s time to mix them together.

Microfluidic mixing makes it easy to formulate monodispersed lipid nanoparticles (LNPs) quickly. Properly designed microfluidic mixers can produce 1 to hundreds of milliliters of LNPs. This simple workflow utilizes a bottom-up approach to LNP synthesis which traps payloads inside nanoparticles by rapid mixing of an aqueous phase and an organic phase in a series of microfluidic channels and wells.

Here’s how it works:

Lock and load
Load your aqueous and organic formulations into containers appropriate for your next step - usually syringes.
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Mix it up

Plug your syringes into a microfluidic mixing chip to start making your LNPs. Pressure moves the aqueous and organic formulations through the channels where they are mixed in microfluidic traps using Dean vortices. These traps are arranged in series where bifurcation allows a portion of the fluid to bypass the trap and recombine with the rest of the material downstream.

This controlled, rapid, chaotic mixing occurs simultaneously in all wells creating consistent, predictable, and high-quality LNPs.

 

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Find your size

Making changes to the flow rate ratio (FRR) and the total flow rate (TFR) lets you control the size of your LNP. This can be an iterative process until you find the settings that are needed to make the right size LNP for the target application.

You can use analytical methods like DLS to check size and polydispersity and a payload-specific assay to look at encapsulation efficiency.

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Same batch to batch

Once you’ve optimized your flow rate, microfluidic mixing tools can make a wide range of volumes with high accuracy and reproducibility.

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Nunchuck

Nunchuck is the first and only platform that combines two key steps needed to make the perfectly-sized LNP – total flow rate screening and LNP formulation. Screen 8 total flow rates (TFRs) in just 10 minutes to find your sweet spot fast, then jump straight into making 0.5 to 200 mL of your LNPs. Dump the one‑flow-rate-at-a-time, back and forth workflows for the ultimate one‑and‑done LNP maker.

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More info

Lipid nanoparticle researchers can now get total flow rate screening and large volume LNP formulation from the same easy-to-use solution, Nunchuck. Have a question or ready to find out more?