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Updated: May 22, 2025
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Formulating and Characterizing Lipid Nanoparticles for Gene Delivery using a Microfluidic Mixing Platform
Published on: February 25, 2021
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Optimizing Microfluidic Channel Design with Tilted Rectangular Baffles for Enhanced mRNA-Lipid Nanoparticle
Mingzhi Yu1, Dongsheng Liu2,3, Pranay Shah1
1Centre of Micro/Nano Manufacturing Technology (MNMT-Dublin), School of Mechanical & Materials Engineering, University College Dublin, Dublin 4 D04 V1W8, Ireland.
ACS Biomaterials Science & Engineering
|May 21, 2025
Summary
Researchers optimized microfluidic chips for producing lipid nanoparticles (LNPs) for RNA therapeutics. A 70° baffle angle and 150 µm length design improved LNP production and transfection efficiency.
Area of Science:
- Biotechnology
- Materials Science
- Chemical Engineering
Background:
- RNA therapeutics offer novel treatment strategies but face challenges in stability and delivery.
- Lipid-based nanoparticles (LNPs) are essential for encapsulating and delivering RNA payloads.
- Microfluidic fabrication offers precise control for LNP production.
Purpose of the Study:
- To design, simulate, and optimize microfluidic chip configurations for efficient LNP fabrication.
- To identify optimal microfluidic channel designs for high mixing efficiency and scalability in LNP production.
- To validate simulation findings through experimental fabrication and assess LNP transfection efficiency.
Main Methods:
- Computational fluid dynamics (CFD) simulations were used to evaluate various microfluidic channel designs with flow focusing and tilted rectangular baffles.
- Poly(dimethylsiloxane) (PDMS) microfluidic chips were fabricated based on simulation results.
- Lipid nanoparticles (LNPs) encapsulating green fluorescent protein mRNA (GFP mRNA) were prepared and their transfection efficiency was evaluated *in vitro*.
Main Results:
- Microfluidic channels with baffle angles between 70-90° showed high mixing efficiency.
- A 70° baffle angle and 150 µm baffle length provided optimal mixing and acceptable pressure drop.
- The optimal microfluidic design yielded LNPs with the highest *in vitro* transfection efficiency at an N/P ratio of 5.6.
Conclusions:
- Optimized microfluidic chip design enhances LNP production for RNA therapeutics.
- The developed method offers a scalable and reproducible approach for LNP fabrication.
- This research facilitates the clinical translation of RNA-based medicines.
