The relationship between the microstructure of a porous medium and the observed flow distribution is still a puzzle. We resolve it with an analytical model, where the local correlations between adjacent pores, which determine the distribution of flows propagated from one pore downstream, predict the flow distribution. Numerical simulations of a two-dimensional porous medium verify the model and clearly show the transition of flow distributions from δ-function-like via Gaussians to exponential with increasing disorder. Comparison to experimental data further verifies our numerical approach.

DNA origami is designed by folding DNA strands at the nanoscale with arbitrary control. Due to its inherent biological nature, DNA origami is used in drug delivery for enhancement of synergism and multidrug resistance inhibition, cancer diagnosis, and many other biomedical applications, where it shows great potential. However, the inherent instability and low payload capacity of DNA origami restrict its biomedical applications. Here, this paper reports the fabrication of an advanced biocompatible nano‐in‐nanocomposite, which protects DNA origami from degradation and facilities drug loading. The DNA origami, gold nanorods, and molecular targeted drugs are co‐incorporated into pH responsive calcium phosphate [Ca3(PO4)2] nanoparticles. Subsequently, a thin layer of phospholipid is coated onto the Ca3(PO4)2 nanoparticle to offer better biocompatibility. The fabricated nanocomposite shows high drug loading capacity, good biocompatibility, and a photothermal and pH‐responsive payload release profile and it fully protects DNA origami from degradation. The codelivery of DNA origami with cancer drugs synergistically induces cancer cell apoptosis, reduces the multidrug resistance, and enhances the targeted killing efficiency toward human epidermal growth factor receptor 2 positive cells. This nanocomposite is foreseen to open new horizons for a variety of clinical and biomedical applications.

Self‐healing polymers crosslinked by solely reversible bonds are intrinsically weaker than common covalently crosslinked networks. Introducing covalent crosslinks into a reversible network would improve mechanical strength. It is challenging, however, to apply this concept to “dry” elastomers, largely because reversible crosslinks such as hydrogen bonds are often polar motifs, whereas covalent crosslinks are nonpolar motifs. These two types of bonds are intrinsically immiscible without cosolvents. Here, we design and fabricate a hybrid polymer network by crosslinking randomly branched polymers carrying motifs that can form both reversible hydrogen bonds and permanent covalent crosslinks. The randomly branched polymer links such two types of bonds and forces them to mix on the molecular level without cosolvents. This enables a hybrid “dry” elastomer that is very tough with fracture energy 13500 Jm−2 comparable to that of natural rubber. Moreover, the elastomer can self‐heal at room temperature with a recovered tensile strength 4 MPa, which is 30% of its original value, yet comparable to the pristine strength of existing self‐healing polymers. The concept of forcing covalent and reversible bonds to mix at molecular scale to create a homogenous network is quite general and should enable development of tough, self‐healing polymers of practical usage.

The cytoskeleton is the major mechanical structure of the cell; it is a complex, dynamic
biopolymer network comprising microtubules, actin, and intermediate filaments. Both the
individual filaments and the entire network are not simple elastic solids but are instead highly nonlinear structures. Appreciating the mechanics of biopolymer networks is key to under-
standing the mechanics of cells. Here, we review the mechanical properties of cytoskeletal polymers and discuss the implications for the behavior of cells.

We demonstrate an acoustic wave driven microfluidic cell sorter that combines advantages of multilayer device fabrication with planar surface acoustic wave excitation. We harness the strong vertical component of the refracted acoustic wave to enhance cell actuation by using an asymmetric flow field to increase cell deflection. Precise control of the 3-dimensional flow is realized by topographical structures implemented on the top of the microchannel. We experimentally quantify the effect of the structure dimensions and acoustic parameter. The design attains cell sorting rates and purities approaching those of state of the art fluorescence-activated cell sorters with all the advantages of microfluidic cell sorting.

At the triple point of a repulsive screened Coulomb system, a fcc crystal, a bcc crystal, and a fluid phase coexist. At their intersection, these three phases form a liquid groove, the triple junction. Using confocal microscopy, we resolve the triple junction on a single-particle level in a model system of charged PMMA colloids in a nonpolar solvent. The groove is found to be extremely deep and the incommensurate solid-solid interface to be very broad. Thermal fluctuations hence appear to dominate the solid-solid interface. This indicates a very low interfacial energy. The fcc-bcc interfacial energy is quantitatively determined based on Young’s equation and, indeed, it is only about 1.3 times higher than the fcc-fluid interfacial energy close to the triple point.

Double emulsions with a hierarchical core-shell structure have great potential in various applications, but their broad use is limited by their instability. To improve stability, water-in-oil-in-water (W/O/W) emulsions with an ultrathin oil layer of several hundred nanometres were produced by using a microcapillary device. The effects of various parameters on the generation of ultrathin-shell double emulsions and their droplet size were investigated, including the proper combinations of inner, middle and outer phases, flow rates and surfactants. The surfactant in the middle oil phase was found to be critical for the formation of the ultrathin-shell double emulsions. Furthermore, the stability of these double emulsions can be notably improved by increasing the concentration of the surfactant, and they can be stable for months. This opens up new opportunities for their future applications in cosmetics, foods and pharmaceuticals.

Cells actively probe and respond to the stiffness of their surroundings. Since mechanosensory cells in connective tissue are surrounded by a disordered network of biopolymers, their in vivo mechanical environment can be extremely heterogeneous. Here we investigate how this heterogeneity impacts mechanosensing by modelling the cell as an idealized local stiffness sensor inside a disordered fibre network. For all types of networks we study, including experimentally-imaged collagen and fibrin architectures, we find that measurements applied at different points yield a strikingly broad range of local stiffnesses, spanning roughly two decades. We verify via simulations and scaling arguments that this broad range of local stiffnesses is a generic property of disordered fibre networks. Finally, we show that to obtain optimal, reliable estimates of global tissue stiffness, a cell must adjust its size, shape, and position to integrate multiple stiffness measurements over extended regions of space.

Biocompatible microcapsules with a water core are widely used to encapsulate hydrophilic actives. Here, a facile method to fabricate monodisperse biocompatible microcapsules with a water core in large quantity is reported. Microfluidic technology is utilized to emulsify the inner aqueous phase containing the shell polymer into monodisperse drops in the outer oil phase. As the cosolvent in the inner aqueous phase diffuses into the outer oil phase, the solubility of the shell polymer decreases, which eventually precipitates. Since the shell polymer, shellac, contains both hydrophilic and hydrophobic groups, it tends to wet both the inner aqueous phase and the outer oil phase, thus forming a solid shell at the periphery of the drop. We show that the diffusion rate of hydrophilic molecules encapsulated in the water core decreases as their molecular weight increases and the property of the microcapsules could further be modified by polyelectrolyte multilayer coating. These microcapsules are fabricated using FDA-approved polymer and non-toxic solvents and are of great use in drugs, cosmetics and foods.

Compressed monodisperse emulsions in confined space exhibit highly ordered structures. The influence of the volume fraction and the confinement geometry on the organized structures is investigated and the mechanism by which structural transition occurs is studied. Based on the understanding of ordering behavior of compressed emulsions, a simple and high‐throughput method to fabricate monodisperse polyhedral microgels using the emulsions as the template is developed. By controlling the geometry of the confined spaces, a variety of shapes such as hexagonal prism, Fejes Toth honeycomb prism, truncated octahedron, pyritohedron, and truncated hexagonal trapezohedron are implemented. Moreover, the edge sharpness of each shape is controllable by adjusting the drop volume fraction. This design principle can be readily extended to other shapes and materials, and therefore provides a useful means to create polyhedral microparticles for both fundamental study and practical applications.

In this study, a single‐step microfluidic approach is reported for encapsulation of enzymes within microcapsules with ultrathin polymeric shell for controlled release triggered by an osmotic shock. Using a glass capillary microfluidic device, monodisperse water‐in‐oil‐in‐water double emulsion droplets are fabricated with enzymes in the core and an ultrathin middle oil layer that solidifies to produce a consolidated inert polymeric shell with a thickness of a few tens to hundreds of nanometers. Through careful design of microcapsule membranes, a high percentage of cargo release, over 90%, is achieved, which is triggered by osmotic shock when using poly(methyl methacrylate) as the shell material. Moreover, it is demonstrated that compared to free enzymes, the encapsulated enzyme activity is maintained well for as long as 47 days at room temperature. This study not only extends industrial applications of enzymes, but also offers new opportunities for encapsulation of a wide range of sensitive molecules and biomolecules that can be controllably released upon applying osmotic shock.

Microfluidic flow-focusing devices offer excellent control over fluid flow, enabling formation of drops with a narrow size distribution. However, the throughput of microfluidic flow-focusing devices is limited and scale-up through operation of multiple drop makers in parallel often compromises the robustness of their operation. We demonstrate that parallelization is facilitated if the outer phase is injected from the direction opposite to that of the inner phase, because the fluid injection flow rate, where the drop formation transitions from the squeezing into the dripping regime, is shifted towards higher values.

Suspensions of solid micron-scale colloidal particles in liquid solvents are a foundational model system used to explore a wide range of phase transitions, including crystallization, gelation, spinodal decomposition, and the glass transition. One of the most commonly used systems for these investigations is the fluorescent spherical particles of polymethylmethacrylate (PMMA) suspended in a mixture of nonpolar solvents that match the density and the refractive index of the particles to minimize sedimentation and scattering. However, the particles can swell in these solvents, changing their size and density, and may leak the fluorescent dye over days to weeks; this constrains the exploration of slow and kinetically limited processes, such as near-boundary phase separation or the glass transition. In this paper, we produce PMMA colloidal particles that employ polymerizable and photostable cyanine-based fluorescent monomers spanning the range of visible wavelengths and a polymeric stabilizer prepared from polydimethylsiloxane, PDMS-graft-PMMA. Using microcalorimetry, we characterize the thermodynamics of an accelerated equilibration process for these dispersions in the buoyancy- and refractive-index-matching solvents. We use confocal differential dynamic microscopy to demonstrate that they behave as hard spheres. The suspended particles are stable for months to years, maintaining fixed particle size and density, and do not leak dye. Thus, these particles enable longer term experiments than may have been possible earlier; we demonstrate this by observing spinodal decomposition in a mixture of these particles with a depletant polymer in the microgravity environment of the International Space Station. Using fluorescence microscopy, we observe coarsening over several months and measure the growth of the characteristic length scale to be a fraction of a picometer per second; this rate is among the slowest observed in a phase-separating system. Our protocols should facilitate the synthesis of a variety of particles.

Droplet microfluidic techniques can perform large numbers of single molecule and cell reactions but often require controlled, periodic flow to merge, split, and sort droplets. Here, we describe a simple method to convert aperiodic flows into periodic ones. Using an oil extraction module, we efficiently remove oil from emulsions to readjust the droplet volume fraction, velocity, and packing, producing periodic flows. The extractor acts as a universal adaptor to connect microfluidic modules that do not operate under identical flow conditions, such as droplet generators, incubators, and merger devices.

Recent advances in cellular profiling have demonstrated substantial heterogeneity in the behaviour of cells once deemed 'identical', challenging fundamental notions of cell 'type' and 'state'. Not surprisingly, these findings have elicited substantial interest in deeply characterizing the diversity, interrelationships and plasticity among cellular phenotypes. To explore these questions, experimental platforms are needed that can extensively and controllably profile many individual cells. Here, microfluidic structures — whether valve-, droplet- or nanowell-based — have an important role because they can facilitate easy capture and processing of single cells and their components, reducing labour and costs relative to conventional plate-based methods while also improving consistency. In this article, we review the current state-of-the-art methodologies with respect to microfluidics for mammalian single-cell 'omics' and discuss challenges and future opportunities.

Perforated single-layered graphene has demonstrated selectivity and flux that is orders of magnitude greater than state-of-the-art polymer membranes. However, only individual graphene sheets with sizes up to tens of micrometers have been successfully fabricated for pressurized permeation studies. Scaling-up and reinforcement of these atomic membranes with minimum cracks and pinholes remains a major hurdle for practical applications. We develop a large-area in situ, phase-inversion casting technique to create 63 cm² high-quality single-layered perforated graphene membranes for ultrafast nanofiltration that can operate at pressures up to 50 bar. This result demonstrates the feasibility of our technique for creating robust large-area, high quality, single-layered graphene and its potential use as a pressurized nanofiltration membrane.

Monodisperse microparticles find applications in a wide range of areas. Generation of such particles of several microns in size at a large scale is a difficult task. This paper reports a proof of concept using a microfluidic device that coaxially flows partially miscible liquids for the production of microparticles. The approach makes use of both the physical forces of the process and the chemical properties of the liquid systems that allows for careful control of the mixing and droplet formation processes. Initial results show that, with this approach, particles with a reasonably narrow size distribution can be produced and liquid miscibility can be used as an additional avenue to manipulate the mean particle size and morphology.

Many newly developed active pharmaceutical ingredients (APIs) are poorly soluble in water and thus have a dissolution-limited bioavailability. The bioavailability of Biopharmaceutical Classification System (BCS) class II APIs increases if they dissolve faster; this can be achieved by increasing their surface-to-volume ratio, for example, through formulation as submicron particles. In this paper, we develop a supersonic spray dryer that enables rapid synthesis of submicron-sized APIs at room temperature. Dispersing gas is accelerated to supersonic velocities in the divergent portion of a de Laval nozzle. The API solution is directly injected in the divergent portion and fully nebulized by impinging high velocity gas and pressure gradients across shocks at the exit of the nozzle. In such a device, we produce crystalline danazol particles with a Sauter mean diameter as small as 188 nm at a production rate up to 200 mg/h. The smallest particles with the narrowest size distributions are formed in overexpanded flows with a shock front close to the nozzle exit. Moreover, we demonstrate the scalability up to 1500 mg/h by increasing the danazol solution concentration; in this case, the Sauter mean diameter of the spray-dried particles increases to 772 nm.

Investigation of host-environment interactions in the gut would benefit from a culture system that maintained tissue architecture yet allowed tight experimental control. We devised a microfabricated organ culture system that viably preserves the normal multicellular composition of the mouse intestine, with luminal flow to control perturbations (e.g., microbes, drugs). It enables studying short-term responses of diverse gut components (immune, neuronal, etc.). We focused on the early response to bacteria that induce either Th17 or RORg⁺ T-regulatory (Treg) cells in vivo. Transcriptional responses partially reproduced in vivo signatures, but these microbes elicited diametrically opposite changes in expression of a neuronal-specific gene set, notably nociceptive neuropeptides. We demonstrated activation of sensory neurons by microbes, correlating with RORg⁺ Treg induction. Colonic RORg⁺ Treg frequencies increased in mice lacking TAC1 neuropeptide precursor and decreased in capsaicin-diet fed mice. Thus, differential engagement of the enteric nervous system may partake in bifurcating pro- or anti-inflammatory responses to microbes.

One of the great challenges in cellular studies is to develop a rapid and biocompatible analytical tool for single-cell analysis. We report a rapid, DNA nanostructure-supported aptamer pull-down (DNaPull) assay under convective flux in a glass capillary for analyzing the contents of droplets with nano- or picoliter volumes. We have demonstrated that the scaffolded aptamer can greatly improve the efficiency of target molecules’ pull down. The convective flux allows complete reaction in <5 min, which is an 18-fold improvement compared to purely diffusive flux (traditional model of the stationary case). This established DNaPull assay can serve as a rapid and sensitive analytical platform for analyzing a variety of bioactive molecules, including small molecules [ATP, limit of detecton (LOD) of 1 μM], a drug (cocaine, LOD of 1 μM), and a biomarker (thrombin, LOD of 0.1 nM). Significantly, the designed microfluidic device compartmentalizes live cells into nanoliter-sized droplets to present single-cell samples. As a proof of concept, we demonstrated that cellular molecules (ATP) from a discrete number of HNE1 cells (zero to five cells) lysed inside nanoliter-sized droplets can be analyzed using our DNaPull assay, in which the intracellular ATP level was estimated to be ∼3.4 mM. Given the rapid assay feature and single-cell sample analysis ability, we believe that our analytical platform of convection-driven DNaPull in a glass capillary can provide a new paradigm in biosensor design and will be valuable for single-cell analysis.