Vortex fluidic regulated phospholipid equilibria involving liposomes down to sub-micelle size assemblies

Conventional channel-based microfluidic platforms have gained prominence in controlling the bottom-up formation of phospholipid based nanostructures including liposomes. However, there are challenges in the production of liposomes from rapidly scalable processes. These have been overcome using a vortex fluidic device (VFD), which is a thin film microfluidic platform rather than channel-based, affording similar to 110 nm diameter liposomes. The high yielding and high throughput continuous flow process has a 45 degrees tilted rapidly rotating glass tube with an inner hydrophobic surface. Processing is also possible in the confined mode of operation which is effective for labelling pre-VFD-prepared liposomes with fluorophore tags for subsequent mechanistic studies on the fate of liposomes under shear stress in the VFD. In situ small-angle neutron scattering (SANS) established the co-existence of liposomes similar to 110 nm with small rafts, micelles, distorted micelles, or sub-micelle size assemblies of phospholipid, for increasing rotation speeds. The equilibria between these smaller entities and similar to 110 nm liposomes for a specific rotational speed of the tube is consistent with the spatial arrangement and dimensionality of topological fluid flow regimes in the VFD. The prevalence for the formation of similar to 110 nm diameter liposomes establishes that this is typically the most stable structure from the bottom-up self-assembly of the phospholipid and is in accord with dimensions of exosomes. Liposomes are formed in high yield under continuous flow in the vortex fluidic device with in situ SANS establishing the co-existence of similar to 110 nm liposomes, rafts, micelles, or sub-micelle size assemblies for increasing rotational speed.