We describe the manufacture of low-cost microfluidic systems to produce nanoscale liposomes with highly uniform size distributions (i.e., low polydispersity indexes (PDI)) and acceptable colloidal stability. This was achieved by exploiting a Y-junction device followed by a serpentine micromixer geometry to facilitate the diffusion between the mixing phases (i.e., continuous and dispersed) via advective processes. Two different geometries were studied. In the first one, the microchannels were engraved with a laser cutting machine on a polymethyl methacrylate (PMMA) sheet and covered with another PMMA sheet to form a two-layer device. In the second one, microchannels were not engraved but through-hole cut on a PMMA sheet and encased by a top and a bottom PMMA sheet to form a three-layer device. The devices were tested out by putting in contact lipids dissolved in alcohol as the dispersed phase and water as the continuous phase to self-assemble the liposomes. By fixing the total flow rate (TFR) and varying the flow rate ratio (FRR), we obtained most liposomes with average hydrodynamic diameters ranging from 188 ± 61 to 1312 ± 373 nm and 0.30 ± 0.09 PDI values. Such liposomes were obtained by changing the FRR from 5:1 to 2:1. Our results approached those obtained by conventional bulk synthesis methods such as a thin hydration bilayer and freeze-thaw, which produced liposomes with diameters ranging from 200 ± 38 to 250 ± 38 nm and 0.30 ± 0.05 PDI values. The produced liposomes might find several potential applications in the biomedical field, particularly in encapsulation and drug delivery.

中文翻译：

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低成本微流控系统合成纳米脂质体

我们描述了低成本微流控系统的制造，以生产具有高度均匀的尺寸分布（即低多分散指数（PDI））和可接受的胶体稳定性的纳米级脂质体。这是通过利用Y型结装置和蛇形微混合器的几何形状来实现的，以促进对流过程在混合相（即连续和分散）之间扩散。研究了两种不同的几何形状。在第一个中，将微通道用激光切割机雕刻在聚甲基丙烯酸甲酯（PMMA）板上，并用另一块PMMA板覆盖，以形成两层设备。在第二个中，没有雕刻微通道，而是在PMMA板上切割了通孔，并用顶部和底部的PMMA板包裹起来以形成三层设备。通过将溶解在乙醇中的接触脂质（作为分散相）和水（作为连续相）进行接触，以使脂质体自组装，对设备进行测试。通过固定总流速（TFR）和改变流速比（FRR），我们获得了大多数脂质体，其平均流体动力学直径范围为188±61至1312±373 nm，PDI值为0.30±0.09。通过将FRR从5：1更改为2：1获得此类脂质体。我们的结果接近通过常规本体合成方法（如薄水合双层和冻融）获得的结果，这些方法生产的脂质体直径范围为200±38至250±38 nm，PDI值为0.30±0.05。产生的脂质体可能在生物医学领域，特别是在封装和药物递送中发现几种潜在的应用。