Behavioral universality across size scales: Glassy materials are characterized by a lack of long-range order, whether at the atomic level or at much larger length scales. But to what extent is their commonality in the behavior retained at these different scales? Cubuk et al. used experiments and simulations to show universality across seven orders of magnitude in length. Particle rearrangements in such systems are mediated by defects that are on the order of a few particle diameters. These rearrangements correlate with the material's softness and yielding behavior. Science , this issue p. 1033
Nucleic acids, such as messenger RNAs, antisense oligonucleotides, and short interfering RNAs, hold great promise for treating previously ‘undruggable’ diseases. However, there are numerous biological barriers that hinder nucleic acid delivery to target cells and tissues. While lipid nanoparticles (LNPs) have been developed to protect nucleic acids from degradation and mediate their intracellular delivery, it is challenging to predict how alterations in LNP formulation parameters influence delivery to different organs. In this study, we utilized high-throughput in vivo screening to probe for structure–function relationships of intravenously administered LNPs along with quartz crystal microbalance with dissipation monitoring (QCM-D) to measure the binding affinity of LNPs to apolipoprotein E (ApoE), a protein implicated in the clearance and uptake of lipoproteins by the liver. High-throughput in vivo screening of a library consisting of 96 LNPs identified several formulations containing the helper lipid 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) that preferentially accumulated in the liver, while identical LNPs that substituted DOPE with the helper lipid 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) preferentially accumulated in the spleen. Using QCM-D, it was found that one DOPE-containing LNP formulation (LNP 42) had stronger interactions with ApoE than an identical LNP formulation that substituted DOPE with DSPC (LNP 90). In order to further validate our findings, we formulated LNP 42 and LNP 90 to encapsulate Cy3-siRNA or mRNA encoding for firefly luciferase. The DSPC-containing LNP (LNP 90) was found to increase delivery to the spleen for both siRNA (two-fold) and mRNA (five-fold). In terms of liver delivery, the DOPE-containing LNP (LNP 42) enhanced mRNA delivery to the liver by two-fold and improved liver transfection by three-fold. Understanding the role of the helper lipid in LNP biodistribution and ApoE adsorption may aid in the future design of LNPs for nucleic acid therapeutics.
Janus particles are colloids that have both hydrophilic and hydrophobic faces. Recent advances in particle synthesis enable the generation of geometrically and chemically anisotropic Janus particles with high uniformity and precision. These amphiphilic particles are similar to molecular surfactants in many aspects; they self-assemble in bulk media and also readily attach to fluid interfaces. These particles, just like molecular surfactants, could potentially function as effective stabilizers for various multiphasic systems such as emulsions and foams. In particular, just as the shape and chemical composition have a significant impact on the surfactancy of molecular amphiphiles, the ability to control the shape and wetting properties of Janus particles could provide a unique opportunity to control their surface activity. In this review, we first examine the recent developments in using amphiphilic Janus particles as colloid surfactants to stabilize multiphasic mixtures such as emulsions. These results have motivated a number of detailed investigations aimed at understanding the behaviour of Janus particles at fluid–fluid interfaces at the microscopic level, which we highlight. This review also discusses the importance of controlling the shape of Janus particles, which has a drastic impact on their behaviour at fluid interfaces. We conclude this review by presenting outlook on the future directions and outstanding problems that warrant further study to fully enable the utilization of Janus particles as colloid surfactants in practical applications.
We study the behaviour of Janus particles at an oil–water interface. Amphiphilic Janus particles exhibit attractive interactions at the fluid–fluid interface. The attractive interactions are likely due to the pinning of contact line around the diffuse boundary between the two hemispheres. The undulation of the three-phase contact line around Janus particles leads to quadrupolar capillary interactions, which we confirm by measuring the interparticle forces. We also show that Janus particles with two negatively charged-hydrophilic hemispheres show repulsive interactions.
Droplet-based microfluidics has led to transformational new approaches in diverse areas including materials synthesis and high-throughput biological assays. However, the translation of droplet microfluidics technology into commercial applications requires scale-up of droplet generation from the laboratory (<10 mL h−1) to the industrial (>1 L h−1) scale. To address this challenge, we develop a three-dimensional monolithic elastomer device (3D MED) for mass production of monodisperse emulsion droplets. Using double-sided imprinting, 3D microchannels are formed in a single elastomer piece that has 1000 parallel flow focusing generators (k-FFGs). Compared to previous work that parallelizes droplet generation, the 3D MED eliminates the needs for alignment and bonding of multiple pieces and thus makes it possible to achieve the high flow rates and pressure necessary for the kilo-scale generation of droplets. Using this approach, we demonstrate mass production of water-in-oil (W/O) emulsion droplets at production rates as high as 1.5 L h−1 (>30 billion 45 μm diameter droplets per hour), with a coefficient of variation of droplet diameter of only 6.6%. Because of the simplicity, robustness, and manufacturability of our 3D MED architecture, it is well suited to bridge the gap between the continuously growing library of promising microfluidic technologies to generate microparticles that have been demonstrated in laboratory settings and their successful application in industry.