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Pharmaceutics
Volume 17
Issue 5
10.3390/pharmaceutics17050566
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Article

Low-Cost Microfluidic Mixers: Are They up to the Task?

by
Jade Forrester
1,
Callum G. Davidson
1,
May Blair
2,
Lynn Donlon
2,
Daragh M. McLoughlin
2,
Chukwuebuka R. Obiora
2,
Heather Stockdale
2,
Ben Thomas
2,
Martina Nutman
3,
Sarah Brockbank
3,
Zahra Rattray
1 and
Yvonne Perrie
1,*
1
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, UK
2
Centre for Process Innovation (CPI), Coxon Building, John Walker Rd., Sedgefield, Stockton-on-Tees TS21 3FE, UK
3
Medicines Discovery Catapult, Alderley Park, Macclesfield SK10 4ZF, UK
*
Author to whom correspondence should be addressed.
Pharmaceutics 2025, 17(5), 566; https://doi.org/10.3390/pharmaceutics17050566
Submission received: 22 March 2025 / Revised: 16 April 2025 / Accepted: 22 April 2025 / Published: 25 April 2025
(This article belongs to the Section Nanomedicine and Nanotechnology)
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Abstract

Background/Objectives: Microfluidic mixing has become the gold standard procedure for manufacturing nucleic acid lipid-based delivery systems, offering precise control over critical process parameters. The choice and design of microfluidic mixers are often seen as a key driving force affecting the critical quality attributes of the resulting lipid nanoparticles (LNPs). Methods: This study aimed to evaluate LNPs manufactured using two low-cost microfluidic mixers alongside manual mixing (pipette mixing (PM)), followed by characterization studies using orthogonal analytics as well as expression studies to establish whether low-cost microfluidic manufacturing methods are suitable for bench-scale and high-throughput research. Results: The results show that all manufacturing methods can produce LNPs with sizes ranging between 95 and 215 nm with high encapsulation (70–100%), and enhanced analytics showed variations between the LNPs produced using the different mixers. Despite these differences, pipette mixing production of LNPs demonstrated its application as a high-throughput screening tool for LNPs, effectively distinguishing between different formulations and predicting consistent expression patterns both in vitro and in vivo. Conclusions: Overall, these results validate the use of low-cost microfluidic mixers without compromising the efficiency and integrity of the resulting LNPs. This study supports the increased accessibility of small-scale LNP manufacturing and high-throughput screening.
Keywords: lipid nanoparticle; mRNA; microfluidic mixing; manufacture; characterization lipid nanoparticle; mRNA; microfluidic mixing; manufacture; characterization
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MDPI and ACS Style

Forrester, J.; Davidson, C.G.; Blair, M.; Donlon, L.; McLoughlin, D.M.; Obiora, C.R.; Stockdale, H.; Thomas, B.; Nutman, M.; Brockbank, S.; et al. Low-Cost Microfluidic Mixers: Are They up to the Task? Pharmaceutics 2025, 17, 566. https://doi.org/10.3390/pharmaceutics17050566

AMA Style

Forrester J, Davidson CG, Blair M, Donlon L, McLoughlin DM, Obiora CR, Stockdale H, Thomas B, Nutman M, Brockbank S, et al. Low-Cost Microfluidic Mixers: Are They up to the Task? Pharmaceutics. 2025; 17(5):566. https://doi.org/10.3390/pharmaceutics17050566

Chicago/Turabian Style

Forrester, Jade, Callum G. Davidson, May Blair, Lynn Donlon, Daragh M. McLoughlin, Chukwuebuka R. Obiora, Heather Stockdale, Ben Thomas, Martina Nutman, Sarah Brockbank, and et al. 2025. "Low-Cost Microfluidic Mixers: Are They up to the Task?" Pharmaceutics 17, no. 5: 566. https://doi.org/10.3390/pharmaceutics17050566

APA Style

Forrester, J., Davidson, C. G., Blair, M., Donlon, L., McLoughlin, D. M., Obiora, C. R., Stockdale, H., Thomas, B., Nutman, M., Brockbank, S., Rattray, Z., & Perrie, Y. (2025). Low-Cost Microfluidic Mixers: Are They up to the Task? Pharmaceutics, 17(5), 566. https://doi.org/10.3390/pharmaceutics17050566

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