Self-regulating microfluidic system for lipid nanoparticle production

Nov 3, 2025Journal of controlled release : official journal of the Controlled Release Society

Self-controlling microfluidic system for making lipid nanoparticles

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mRNA Technology on OpenScience ↗PubMed ↗DOI ↗

Abstract

Data-driven automation may enable fully automated lipid nanoparticle formulation optimization using microfluidic hardware.

Insights from simulations and microfluidic screenings inform machine learning algorithms that predict size and encapsulation efficiency.
A self-regulating microfluidic device integrates computational and experimental efforts for real-time optimization.
The approach leverages low-cost technology to streamline the complex formulation process of lipid nanoparticles.
This proof-of-concept study highlights the potential for rapid formulation parameterization in nanoparticle design.

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Lipid nanoparticles have emerged as valuable gene delivery systems paving the way for next-generation vaccine and cancer therapeutics. Inevitably, this evolution is carried by dissecting and rationalizing the vehicles' complex formulation process. Given the vast design space, in silico methods resemble an elegant and cost-effective optimization approach. Here, we provide a proof-of-concept study on how data-driven automatization leverages rapid formulation parameterization, using readily obtainable, low-cost microfluidic hardware. Insights gained from both computational fluid dynamics simulations and microfluidic screenings are harnessed to derive and complement machine learning algorithms that predict critical quality attributes, such as size and encapsulation efficiency. Subsequently, these models are used to deploy a self-regulating microfluidic device, thereby bridging the gap between our computational and experimental work and enabling fully automated lipid nanoparticle formulation optimization on the fly, with minimal human intervention required. We envision our approach to accelerate the discovery of optimized nanoparticles in future designs.