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 language | English |
|---|---|
| Pages (from-to) | 1202-1212 |
| Number of pages | 11 |
| Journal | Nanoscale Advances |
| Volume | 6 |
| Issue number | 4 |
| DOIs | |
| State | Published - Jan 18 2024 |
Funding
The authors acknowledge support of this work by the Australian Research Council (DP200101105 and DP200101106) for funding support, Australian Nuclear Science & Technology organization ANSTO for the beamtime (proposals 7015,7402 and 13375) to carry out the experiments and their guidance and support throughout this project. The authors acknowledge the Australian Microscopy and Microanalysis Research Facility (AMMRF) and Australian National Fabrication Facility (AMMRF) for SEM, dual target sputter coater and AFM imaging. A portion of this research used resources at the High Flux Isotope Reactor, a DOE Office of Science User Facility operated by the Oak Ridge National Laboratory. Authors also acknowledge Adelaide Microscopy at The University of Adelaide (UoA), South Australia for TEM imaging and Flinders Centre for Innovation in Cancer (FCIC), South Australia for the guidance and support throughout this project. Funding for Bio-SANS is provided by the Office of Biological & Environmental Research in the U.S. Department of Energy's Office of Science.