Low-cost microfluidic mixers : are they up to the task?

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Forrester, Jade and Davidson, Callum G. and Blair, May and Donlon, Lynn and McLoughlin, Daragh M. and Obiora, Chukwuebuka R. and Stockdale, Heather and Thomas, Ben and Nutman, Martina and Brockbank, Sarah and Rattray, Zahra and Perrie, Yvonne (2025) Low-cost microfluidic mixers : are they up to the task? Pharmaceutics, 17 (5). 566. ISSN 1999-4923 (https://doi.org/10.3390/pharmaceutics17050566)

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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.

ORCID iDs

Forrester, Jade, Davidson, Callum G. ORCID logoORCID: https://orcid.org/0009-0003-8736-9918, Blair, May, Donlon, Lynn, McLoughlin, Daragh M., Obiora, Chukwuebuka R., Stockdale, Heather, Thomas, Ben, Nutman, Martina, Brockbank, Sarah, Rattray, Zahra ORCID logoORCID: https://orcid.org/0000-0002-8371-8549 and Perrie, Yvonne ORCID logoORCID: https://orcid.org/0000-0001-8497-2541;
CORE (COnnecting REpositories)