Lipid nanoparticles (LNPs) have revolutionized nucleic acid therapeutics but translating a formulation from lab‑scale screening to industrial production presents significant challenges [1]. Early‑stage development typically uses microfluidic micromixers such as T‑junction, herringbone, baffle and toroidal designs to achieve precise control over LNP characteristics. However, these devices lack the throughput needed for clinical or commercial manufacturing. On the other hand, impinging jet mixers (IJMs) support high‑volume operation and produce LNPs but without a clear methodology to carry over microfluidic‑optimized parameters.
Here, we present a direct comparison of LNPs generated in representative microfluidic geometries versus a standard IJM, under matched lipid formulations and process conditions. We evaluate how each mixing platform influences critical quality attributes across a range of aqueous‑to‑ethanol ratios, total flow rates, buffer concentrations, pH and lipid concentrations. This study aims to define the operating windows in which IJMs can reproduce the particle characteristics observed in microfluidic screening, providing a straightforward path to scale up promising formulations with minimal re‑optimization.
By focusing on the core attributes, our comparative framework is designed to accelerate the translation of new LNP formulations from benchtop discovery to high‑throughput manufacturing, supporting the rapid deployment of next‑generation nanoparticle therapeutics.
This research was supported by the U.S. Food and Drug Administration under the FDA BAA-22-00123 program, Award Number 75F40122C00200.
[1] Mehraji, S. et al., Lab on a Chip 24, 1154–1174 (2024).