An Accessible and Scalable Pipette-Driven Microfluidic Platform for Lipid Nanoparticle Formulation
- 1Sartorius Stedim North America Inc.
Abstract
Advances in lipid nanoparticle (LNP) technology have increased the need for accessible and scalable methods that accelerate low-volume formulation screening. Here, we describe a disposable microfluidic mixer actuated by a positive-displacement pipette equipped with dual-chamber pipette tip, providing volumetric control at a fixed flow rate ratio without external microfluidic pumps. Computational fluid dynamics analysis predicted shorter micromixing times in the high-shear spiral channel than in the low-shear design. Across three benchmark lipid formulations, the high-shear mixer reproducibly generated smaller LNPs with higher mRNA encapsulation efficiency than the low-shear mixer or manual pipetting. Orthogonal characterization further revealed higher particle concentrations, structural features consistent with compact particles, more uniform mRNA loading, and a lower empty-particle fraction. LNPs prepared using the selected high-shear mixer mediated functional mRNA delivery in 2D cell cultures, a 3D human liver tissue model, and mice. Integration with a liquid-handling robot enabled automated screening of formulation parameters. Dimensionless mixing-time analysis guided enlargement of the mixer geometry for a separate production system, which produced 75 mL preparations at 150 mL/min with particle size and mRNA encapsulation efficiency comparable to those obtained with the small-scale mixer. This platform provides an accessible, automation-compatible approach to LNP formulation screening and a route to larger-scale production.
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BibTeX
@misc{takeda2026accessible,
title = {{An Accessible and Scalable Pipette-Driven Microfluidic Platform for Lipid Nanoparticle Formulation}},
author = {Y. S. Takeda and F. Wang and X. Gu and J. Forster and H. Hou and P. Hemmati and B. Partopour and L. Maugeri and Y. Kim and S. Apel and R. Norton and J. Finelli and P. Molaei and S. Shafiee and S. Li and J. Lin and C.-w. Chiang and M. Mayo and S. Ayehunie and S. Akbari and H.-Q. Mao and T.-H. Wang and M. Dehghani},
howpublished = {bioRxiv},
year = {2026},
month = nov,
doi = {10.64898/2026.11.06.757988},
url = {https://www.biorxiv.org/content/10.64898/2026.11.06.757988v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - An Accessible and Scalable Pipette-Driven Microfluidic Platform for Lipid Nanoparticle Formulation
AU - Y. S. Takeda
AU - F. Wang
AU - X. Gu
AU - J. Forster
AU - H. Hou
AU - P. Hemmati
AU - B. Partopour
AU - L. Maugeri
AU - Y. Kim
AU - S. Apel
AU - R. Norton
AU - J. Finelli
AU - P. Molaei
AU - S. Shafiee
AU - S. Li
AU - J. Lin
AU - C.-w. Chiang
AU - M. Mayo
AU - S. Ayehunie
AU - S. Akbari
AU - H.-Q. Mao
AU - T.-H. Wang
AU - M. Dehghani
PY - 2026
DA - 2026/11/06
PB - bioRxiv
DO - 10.64898/2026.11.06.757988
UR - https://www.biorxiv.org/content/10.64898/2026.11.06.757988v1
AB - Advances in lipid nanoparticle (LNP) technology have increased the need for accessible and scalable methods that accelerate low-volume formulation screening. Here, we describe a disposable microfluidic mixer actuated by a positive-displacement pipette equipped with dual-chamber pipette tip, providing volumetric control at a fixed flow rate ratio without external microfluidic pumps. Computational fluid dynamics analysis predicted shorter micromixing times in the high-shear spiral channel than in the low-shear design. Across three benchmark lipid formulations, the high-shear mixer reproducibly generated smaller LNPs with higher mRNA encapsulation efficiency than the low-shear mixer or manual pipetting. Orthogonal characterization further revealed higher particle concentrations, structural features consistent with compact particles, more uniform mRNA loading, and a lower empty-particle fraction. LNPs prepared using the selected high-shear mixer mediated functional mRNA delivery in 2D cell cultures, a 3D human liver tissue model, and mice. Integration with a liquid-handling robot enabled automated screening of formulation parameters. Dimensionless mixing-time analysis guided enlargement of the mixer geometry for a separate production system, which produced 75 mL preparations at 150 mL/min with particle size and mRNA encapsulation efficiency comparable to those obtained with the small-scale mixer. This platform provides an accessible, automation-compatible approach to LNP formulation screening and a route to larger-scale production.
ER -