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Related Experiment Video

Updated: Apr 9, 2026

Formulating and Characterizing Lipid Nanoparticles for Gene Delivery using a Microfluidic Mixing Platform
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Microfluidic Mixing: A General Method for Encapsulating Macromolecules in Lipid Nanoparticle Systems.

Alex K K Leung1, Yuen Yi C Tam1, Sam Chen1

  • 1Department of Biochemistry and Molecular Biology, The University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z3.

The Journal of Physical Chemistry. B
|June 19, 2015
PubMed
Summary

Microfluidic mixing efficiently produces lipid nanoparticles (LNP) with tunable structures for small interfering RNA (siRNA). This technique also successfully encapsulates larger molecules like mRNA and DNA, and even gold nanoparticles.

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Area of Science:

  • Biotechnology
  • Materials Science
  • Nanotechnology

Background:

  • Lipid nanoparticles (LNP) are crucial for delivering nucleic acids.
  • Microfluidic mixing is an efficient method for LNP manufacturing.
  • Previous studies indicate nanostructured cores in LNP-siRNA systems.

Purpose of the Study:

  • To investigate how lipid composition affects LNP-siRNA structure.
  • To determine if microfluidic mixing can encapsulate macromolecules larger than siRNA.
  • To demonstrate the versatility of microfluidic mixing for nanoparticle encapsulation.

Main Methods:

  • Microfluidic mixing for LNP production.
  • Cryo-transmission electron microscopy (cryo-TEM) for structural analysis.
  • Molecular simulations for structural prediction.

Main Results:

  • LNP-siRNA structure transitions towards a bilayer as DSPC content increases.
  • Microfluidic mixing successfully encapsulated mRNA (1.7 kb) and plasmid DNA (6 kb).
  • Negatively charged gold nanoparticles (5 nm) were encapsulated, forming a 'currant bun' morphology.

Conclusions:

  • LNP nanostructure is tunable via lipid composition, offering a continuum of structures.
  • Microfluidic mixing is a versatile technique for encapsulating diverse molecules and nanoparticles within LNPs.
  • The 'currant bun' morphology of gold-containing LNP is consistent with predicted LNP-siRNA structures.