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

Nikita Joseph, Marzieh Mirzamani, Tarfah Abudiyah, Ahmed Hussein Mohammed Al-Antaki, Matt Jellicoe, David P. Harvey, Emily Crawley, Clarence Chuah, Andrew E. Whitten, Elliot Paul Gilbert, Shuo Qian, Lilin He, Michael Z. Michael, Harshita Kumari, Colin L. Raston

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Abstract

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 ∼110 nm diameter liposomes. The high yielding and high throughput continuous flow process has a 45° 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 ∼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 ∼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 ∼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.

Original languageEnglish
Pages (from-to)1202-1212
Number of pages11
JournalNanoscale Advances
Volume6
Issue number4
DOIs
Publication statusPublished - 18 Jan 2024

Keywords

  • Liposomes
  • Vortex fluidic device
  • Microfluidic platforms

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