The recent advances in nanomaterials’ production by microfluidics with high throughput became critical for industry-scale production. Numerical simulation has been part of this development, allowing faster and more detailed study of the process that would be costly only experimentally. Here, we investigated the diffusion and chaotic advection effects on cationic and stealth liposome production in a 3D multihelical chaotic-advection microfluidic device. Suitable conditions for chaotic advection were primarily investigated with computational fluid dynamics (CFD) assessing diverse flow rate ratio (FRR) and total flow rate (TFR). The results showed that Reynolds ≈ 100 and Dean number > 50 can trigger chaotic advection for this device, corresponding to a TFR of 5 mL/min. We produced the liposomes in the same conditions as the simulations to evaluate the impact of these parameters on the colloidal physicochemical properties. A clear difference was shown between TFR ≤ 1 and TFR ≥ 5 mL/min for size and polydispersity (PDI). An increase in PDI was observed for FRR 10, in which the mixing index (M.I.) played an important role. The effect of composition proved an important factor, as stealth liposomes were not deeply affected by TFR change. Cryo-Transmission Electron Microscopy (Cryo-TEM) analysis showed that both cationic and stealth liposomes resulted in unilamellar liposomes. Coupling numerical simulation with experimental characterization proved an efficient process evaluation in microfluidics. Finally, the high mass throughput (2.8 g/h) with the chaotic advection microfluidic device shows a potential microchip for industrial scale-up and parallelization.

中文翻译：

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用于脂质体合成的 3D 多螺旋微流体中混沌平流和扩散混合效应的数值和实验研究


高通量微流体生产纳米材料的最新进展对于工业规模生产变得至关重要。数值模拟已成为这一发展的一部分，它允许对这一过程进行更快、更详细的研究，而这在实验上成本高昂。在这里，我们研究了 3D 多螺旋混沌平流微流体装置中的扩散和混沌平流对阳离子和隐形脂质体生产的影响。主要通过计算流体动力学（CFD）评估不同的流量比（FRR）和总流量（TFR）来研究混沌平流的合适条件。结果表明，雷诺数 ≈ 100 且 Dean 数 > 50 可以触发该装置的混沌平流，对应于 5 mL/min 的 TFR。我们在与模拟相同的条件下生产脂质体，以评估这些参数对胶体理化性质的影响。 TFR ≤ 1 和 TFR ≥ 5 mL/min 之间的粒径和多分散性 (PDI) 存在明显差异。 FRR 10 中观察到 PDI 增加，其中混合指数 (M.I.) 发挥了重要作用。事实证明，成分的影响是一个重要因素，因为隐形脂质体并未受到 TFR 变化的深刻影响。冷冻透射电子显微镜（Cryo-TEM）分析表明，阳离子脂质体和隐形脂质体均形成单层脂质体。数值模拟与实验表征的结合证明了微流体的有效过程评估。最后，混沌平流微流体装置的高质量吞吐量（2.8 g/h）显示了用于工业放大和并行化的潜在微芯片。