Significance: Microfluidic systems promise to improve the analysis and synthesis of materials, biological or otherwise, by lowering the required volume of fluid samples, offering a tightly controlled fluid-handling environment, and simultaneously integrating various chemical processes. To build these systems, designers depend on microfabrication techniques that restrict them to arranging their designs in two dimensions and completely fabricating their design in a single step. This study introduces modular, reconfigurable components containing fluidic and sensor elements adaptable to many different microfluidic circuits. These elements can be assembled to allow for 3D routing of channels. This assembly approach allows for the application of network analysis techniques like those used in classical electronic circuit design, facilitating the straightforward design of predictable flow systems.
Oxidation of unsaturated lipids in cellular membranes has been shown to cause severe membrane damage and potentially cell death. The presence of oxidized lipid species in the membrane is known to cause changes in membrane properties, such as decreased fluidity. This study uses giant unilamellar vesicles (GUVs) to measure passive transport across membranes containing defined concentrations of oxidized lipid species. GUVs consisting of a saturated phospholipid, an unsaturated phospholipid, and cholesterol were used as model membranes. By replacing defined amounts of the unsaturated lipid with a corresponding oxidized product, the oxidation process could be mimicked, yielding vesicles of varying oxidized lipid concentration. Oxidized lipid concentration was varied from 0 mol% to 18 mol% of the total lipid concentration. Passive transport of PEG12-NBD, an uncharged fluorescent molecule, was measured using a microfluidic trap to capture the GUVs and spinning disk confocal microscopy (SDCM) to track the transport of a fluorescent species in the equatorial plane of each GUV. Membrane permeability was determined by fitting the resulting concentration profiles to a finite difference model of diffusion and permeation around and through the membrane. Experiments showed three permeability regimes. Without oxidation, transport was slow, with a measured permeability on the order of 1.5 × 10−6 cm s−1. At 2.5–10% oxidized species permeation was fast (1.5 × 10−5 cm s−1). Above 12.5% oxidized species, the bilayer was disrupted by the formation of pore defects. As passive transport is an important mechanism for drug delivery, understanding the relationship between oxidation and permeation could provide insight into the pharmaceutical characteristics of tissues with oxidative damage.
2 January 2020 in Journal of the American Chemical Society
Synthetic lipid bilayers in a giant unilamellar vesicle (GUV) format were used to study potentially harmful interactions between nanoparticles and biomembranes. Confocal fluorescence microscopy shows that 20 nm polystyrene nanoparticles with cationic surfaces adhere strongly to these lipid bilayer membranes. This adhesion is sensitive to the ionic strength of the surrounding medium and is independent of the lipid composition of the membrane, indicating that it is driven by nonspecific electrostatic interactions. Nanoparticles bound to the GUV membrane form extended protrusions that incorporate the membrane lipids. As the membrane material is pulled into these protrusions, the diameter of the GUV shrinks. This process is accompanied by the formation of transient pores in the membrane, as indicated by the leakage of high-molecular weight polymers from the GUV interior. There is an upper limit to the molecular weight of polymer that will leak through these pores; based on this size limit, the pore diameter can be estimated as 18–27 nm. These results suggest that nanoparticle adhesion imposes surface tension on biomembranes via a steric crowding mechanism, leading to poration. The phenomenon is potentially a physiologically relevant mode of interaction between nanoparticles and biomembranes, and may help explain observed plasma membrane permeabilization in the presence of broad classes of nanoparticles.
The translation of batch chemistries onto continuous flow platforms requires addressing the issues of consistent fluidic behaviour, channel fouling and high-throughput processing. Droplet microfluidic technologies reduce channel fouling and provide an improved level of control over heat and mass transfer to control reaction kinetics. However, in conventional geometries, the droplet size is sensitive to changes in flow rates. Here we report a three-dimensional droplet generating device that exhibits flow invariant behaviour and is robust to fluctuations in flow rate. In addition, the droplet generator is capable of producing droplet volumes spanning four orders of magnitude. We apply this device in a parallel network to synthesize platinum nanoparticles using an ionic liquid solvent, demonstrate reproducible synthesis after recycling the ionic liquid, and double the reaction yield compared with an analogous batch synthesis.