Flow-Driven Control of Lipid Nanoparticle Properties: Performance Assessment of Laminar Micromixers

Micromixing plays a critical role in nanomedicine manufacturing, particularly in the scalable production of lipid nanoparticles (LNPs). While various microfluidic-based mixers have been developed for LNP fabrication, the flow-driven mechanisms that govern stable nanoparticle formation remain poorly understood, especially under high Reynolds number (Re) relevant to industrial throughput. In this study, we present a comprehensive experimental evaluation of three laminar micromixers used for LNP production, combining three complementary optical diagnostics to measure both flow and concentration fields. We employ micro-laser induced fluorescence (µ-LIF) to visualize bulk mixing patterns, and micro-particle image velocimetry (µ-PIV) with frame straddling to resolve high-Re flow structures. To address the limited applicability of concentration measurement in micromixing, we develop and implement a novel micro-background oriented schlieren (µ-BOS) capable of capturing sharp refractive index transitions. Our results reveal distinct flow structures and mixing mechanisms across mixer designs at high Re. The µ-BOS measurements further estimate mixing length and time scales, key parameters that link channel geometry to the kinetics of lipid self-assembly and to LNP size and stability. This integrated experimental framework advances the understanding of micromixing under high Re and provides insights for optimizing mixer design and operating conditions for consistent LNP fabrication.