Microfluidic Mixing and the Formation of Nanoscale Lipid Vesicles

Abstract

We investigate the formation of unilamellar lipid vesicles (liposomes) with diameters of tens of nanometers by controlled microfluidic mixing and nanoparticle determination (COMMAND). Our study includes liposome synthesis experiments and numerical modeling of our microfluidic implementation of the batch solvent injection method. We consider microfluidic liposome formation from the perspective of fluid interfaces and convective-diffusive mixing, as we find that bulk fluid flow parameters including hydrodynamically focused alcohol stream width, final alcohol concentration, and shear stress do not primarily determine the vesicle formation process. Microfluidic device geometry in conjunction with hydrodynamic flow focusing strongly influences vesicle size distributions, providing a coarse method to control liposome size, while total flow rate allows fine-tuning the vesicle size in certain focusing regimes. Although microfluidic liposome synthesis is relatively simple to implement experimentally, numerical simulations of the mixing process reveal a complex system of fluid flow and mass transfer determining the formation of nonequilibrium vesicles. These results expand our understanding of the microfluidic environment that controls liposome self-assembly and yield several technological advances for the on-chip synthesis of nanoscale lipid vesicles.

Preparation of biodegradable polymeric nanoparticles for pharmaceutical applications using glass capillary microfluidics

“…Triple runs were carried out on each experiment to check reproducibility of the particle sizes and only small within-runs variations were observed, as indicated by small error bars. The opposite results were obtained by Jahn et al (2010) in microfluidic preparation of liposomes, with smaller vesicle sizes obtained at smaller total flow rates. The minimum size of both PLA and PCL particles in a coflow device was less than 250 nm and was achieved at or aq Q Q / =10 and for a 60-m orifice size.…”

“…Therefore, a larger number of nuclei will lead to smaller size of NPs. The smaller particle sizes at higher aqueous-to-organic volume ratios were also obtained by Laouini et al (2013aLaouini et al ( , 2013bLaouini et al ( , 2013c in the production of liposomes and polymeric micelles in membrane contactors and by Jahn et al (2010) in the formation of liposomes in planar flow focusing microfluidic mixers.…”

Microfluidic synthesis of multifunctional liposomes for tumour targeting

“…Subsequently, these lipid discs bend to reduce the exposure of the hydrophobic lipid chain to the hydrophilic buffer and finally close into spherical liposomes [11]. This single-step method offers better control over the properties of liposomes, such as particle size, size distribution and surface properties (PEGylation and targeting ligand) [11][12][13][14]. More importantly, this method can be easily scaled up.…”

Microfluidic hydrodynamic focusing based synthesis of POPC liposomes for model biological systems

“…More recently, a new approach based on hydrodynamic focusing in micro-channels [24] has been developed and successfully applied in synthesis of vesicles of various lipids, as well as other types on nanoparticles [25][26][27][28][29][30]. Microfluidic hydrodynamic focusing (MHF) is conducted by introducing the lipid solution through a central inlet channel of a microfluidic device, and focusing this central stream by the flow of an aqueous solution through two or more side channels [24].…”