(438a) Millifluidic Jet Mixing Reactor for High-Throughput Nanoparticle Manufacturing: A Combined Experimental and Computational Study

Nanoparticles have emerged as transformative agents due to their unique size-dependent physical, chemical, and optical properties. These properties stem primarily from enhanced surface area-to-volume ratios and quantum confinement effects, making size a critical feature of nanoparticle manufacturing. Typically, nanoparticles are produced using batch reactors, where mixing is facilitated through vortexers, sonicators, and magnetic stirrers. However, traditional batch processes often lack proper mixing control, leading to concentration and thermal gradients that result in polydisperse nanoparticles. To produce nanoparticles with low polydispersity, the mixing times should be shorter than reaction times to create conditions that induce homogeneous nucleation followed by limited growth. Continuous processes, such as flash nanoprecipitation [3, 4], offer a path to achieving shorter mixing times and reduced particle polydispersity.

Here, we investigated a Jet Mixing Reactor (JMR) previously employed in gas systems [5, 6] for scalable nanomanufacturing. The JMR consists of two jets impinging on a crossflow with dimensions in the millimeter scale. Larger jet mixers with crossflow have long been operated at high Reynolds (Re) numbers, generating vortical structures whose turbulent decay promotes rapid mixing. In contrast, low Re microfluidic devices using crossflow rely on hydrodynamic focusing or complex internal geometries to create fine multilamellar structures and achieve mixing primarily through diffusion. The JMR, with its millimeter scale dimensions, lies between these two extremes. Thus, it is unclear how changes in characteristic length scales, geometry, and operating conditions relate to mixing times or even whether flow should be treated as laminar, laminar but chaotic, or fully turbulent.

In this work, we combine experimental and computational techniques to characterize mixing in a series of JMRs of decreasing size. The Villermaux-Dushman reactions [1, 2] were used to estimate micro-mixing times as a function of inlet flow rate and reactor size. We complemented experimental mixing time measurements with COMSOL simulations to visualize the flow and concentration fields, calculating mixing times using the mixing index. Under symmetric mixing conditions, mixing times ranged from 5 to 40 milliseconds, showing strong agreement between simulations and experiments (mixing index > 0.95). We then validated our mixing times by synthesizing two nanoparticle systems: polybutylacrylate-b-polyacrylic acid (PBA-PAA) block copolymer micelles and polylactic acid-co-glycolic acid (PLGA) nanoparticles. For PBA-PAA, particle size (~50 nm) became independent of flow at 8mL/min, indicating homogeneous kinetics. The JMR produced PLGA nanoparticles < 300 nm in diameter with high reproducibility and an estimated throughput of 1.3 kg per day. This work establishes a scalable strategy for nanoparticle synthesis using jet-mixing reactors applicable to drug delivery vehicles, core-shell metallic nanoparticles, nanostructured polymers, and quantum dot production, thus advancing the development of next-generation materials for biomedicine, and electronics.

References

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