Numerical and experimental investigation of chaotic advection and diffusion mixing effects in 3D multihelical microfluidics for liposome synthesis

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 approximate to 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.