Chen, R. ; Liu, J. ; Yang, C. ; Weitz, D. A. ; He, H. ; Li, D. ; Chen, D. ; Liu, K. ; Bai, H. Transparent Impact-Resistant Composite Films with Bioinspired Hierarchical Structure. ACS Applied Materials & Interfaces 2019, 11, 23616-23622. Publisher's VersionAbstract
Inspired by the helicoidally organized microstructure of stomatopods’ smasher dactyl club, a type of impact-resistant composite film reinforced with periodic helicoidal nanofibers is designed and fabricated, which reproduces the structural complexity of the natural material. To periodically align nanofibers in a helicoidal structure, an electrospinning system is developed to better control the alignment of electrospun nanofibers. When the nanofiber scaffold is embedded in an epoxy matrix, the presence of a hierarchical structure allows the composite films to achieve properties well beyond their constituents. The composite film exhibits excellent optical transparency and mechanical properties, such as enhanced tensile strength, ductility, and defect tolerance. With elegant design mimicking nature’s hierarchical structure at multilength scales, the composite films could effectively release the impact energy and greatly increase the impact resistance, suggesting that the transparent composite films are promising protective layers suitable for various applications.
Kong, L. ; Chen, R. ; Wang, X. ; Zhao, C. - X. ; Chen, Q. ; Hai, M. ; Chen, D. ; Yang, Z. ; Weitz, D. A. Controlled co-precipitation of biocompatible colorant-loaded nanoparticles by microfluidics for natural color drinks. Lab Chip 2019, 19, 2089-2095. Publisher's VersionAbstract
Natural colorants, which impart a vivid color to food and add additional health benefits, are favored over synthetic colorants; however, their applications are limited by their low solubility in water and low stability. Here, we develop a versatile microfluidic strategy to incorporate natural colorants in shellac nanoparticles with controlled physicochemical properties. The rapid mixing in the microfluidic channels ensures that the mixing time is shorter than the aggregation time, thus providing control over the co-precipitation of the colorant and the polymer. By introducing molecular interactions, colorant nanoaggregates are efficiently embedded in the polymer matrix, forming hierarchical colorant-loaded nanoparticles. The colorant-loaded nanoparticles dispersed in water are transparent and stable over a wide pH range and their polymer matrix also provides a favorable microenvironment that greatly improves the shelf life of the colorants. The improved solubility, stability and bioavailability of the natural colorants suggest that shellac nanoparticles are ideal carriers and the stable, transparent dispersions of biocompatible colorant-loaded nanoparticles in water are well-suited for the development of functional foods, such as natural color drinks.
Hwang, H. ; Weitz, D. A. ; Spaepen, F. Direct observation of crystallization and melting with colloids. Proc. Natl. Acad. Sci. U.S.A. 2019, 116, 1180–1184. Publisher's VersionAbstract
We study the kinetics of crystal growth and melting of two types of colloidal crystals: body-centered cubic (BCC) crystals and face-centered cubic (FCC) crystals. A dielectrophoretic “electric bottle” confines colloids, enabling precise control of the motion of the interface. We track the particle motion, and by introducing a structural order parameter, we measure the jump frequencies of particles to and from the crystal and determine from these the free-energy difference between the phases and the interface mobility. We find that the interface is rough in both BCC and FCC cases. Moreover, the jump frequencies correspond to those expected from the random walk of the particles, which translates to collision-limited growth in metallic systems. The mobility of the BCC interface is greater than that of the FCC interface. In addition, contrary to the prediction of some early computer simulations, we show that there is no significant asymmetry between the mobilities for crystallization and melting.
Zhu, H. ; Nawar, S. ; Werner, J. G. ; Liu, J. ; Huang, G. S. ; Mei, Y. F. ; Weitz, D. A. ; Solovev, A. A. Hydrogel micromotors with catalyst-containing liquid core and shell. J. Phys.: Condens. Matter 2019, 31, 214004. Publisher's VersionAbstract
Methacrylic anhydride-derived hydrogel microcapsules have unique properties, including reversibly tunable permeation, purification, and separation of dissolved molecular species. Endowing these dynamic encapsulant systems with autonomous motion will significantly enhance their efficiency and applicability. Here, hydrogel micromotors are realized using complex water-in-oil-in-water double emulsion drops and oil-in-water emulsion drops from glass capillary microfluidics and subsequent photopolymerization. Three hydrogel micromotor strategies are explored: microcapsules with thin shells and liquid cores with dispersed catalytic Pt nanoparticles, as well as water-cored microcapsules and homogeneous microparticles selectively coated with Ti/Pt catalytic layers. Autonomous motion of hydrogel particles and capsules is realized in hydrogen peroxide solutions, where generated oxygen microbubbles propel the dynamically responsive micromotors. The micromotors are balanced by weight, buoyancy, lateral capillary forces and show specific autonomous behaviours that significantly extend short range dynamic responses of hydrogels. Drop-based microfluidics represent a paradigm shift in the integration of multifunctional subsystems and high-throughput design of chemical micromachines in reasonable quantities towards their desired biomedical, environmental and flow/diffusion microreactor applications.
Montessori, A. ; Lauricella, M. ; Stolovicki, E. ; Weitz, D. A. ; Succi, S. Jetting to dripping transition: Critical aspect ratio in step emulsifiers. Physics of Fluids 2019, 31, 021703. Publisher's VersionAbstract
Fully three-dimensional, time-dependent, direct simulations of the non-ideal Navier-Stokes equations for a two-component fluid shed light into the mechanism which inhibits droplet breakup in step emulsifiers below a critical threshold of the width-to-height (w/h) ratio of the microfluidic nozzle. Below w/h ∼ 2.6, the simulations provide evidence of a smooth topological transition of the fluid from the confined rectangular channel geometry to an isotropic (spherical) expansion of the fluid downstream the nozzle step. Above such threshold, the transition from the inner to the outer space involves a series of dynamical rearrangements which keep the free surface in mechanical balance. Such rearrangements also induce a backflow of the ambient fluid which, in turn, leads to jet pinching and ultimately to its rupture, namely, droplet formation. The simulations show remarkable agreement with the experimental value of the threshold, which is found around w/h ∼ 2.56.
Haney, B. ; Chen, D. ; Cai, L. - H. ; Weitz, D. ; Ramakrishnan, S. Millimeter-Size Pickering Emulsions Stabilized with Janus Microparticles. Langmuir 2019, 35, 4693–4701. Publisher's VersionAbstract

The ability to make stable water-in-oil and oil-in-water millimeter-size Pickering emulsions is demonstrated using Janus particles—particles with distinct surface chemistries. The use of a highly cross-linked hydrophobic polymer network and the excellent water-wetting nature of a hydrogel as the hydrophobic and hydrophilic sides, respectively, permit distinct wettability on the Janus particle. Glass capillary microfluidics allows the synthesis of Janus particles with controlled sizes between 128 and 440 μm and control over the hydrophilic-to-hydrophobic domain volume ratio of the particle from 0.36 to 12.77 for a given size. It is shown that the Janus particle size controls the size of the emulsion drops, thus providing the ability to tune the structure and stability of the resulting emulsions. Stability investigations using centrifugation reveal that particles with the smallest size and a balanced hydrophilic-to-hydrophobic volume ratio (Janus ratio) form emulsions with the greatest stability against coalescence. Particles eventually jam at the interface to form nonspherical droplets. This effect is more pronounced as the hydrogel volume is increased. The large Janus particles permit facile visualization of particle-stabilized emulsions, which result in a better understanding of particle stabilization mechanisms of formed emulsions.

Zhang, H. ; Cui, W. ; Qu, X. ; Wu, H. ; Qu, L. ; Zhang, X. ; Makila, E. ; Salonen, J. ; Zhu, Y. ; Yang, Z. ; et al. Photothermal-responsive nanosized hybrid polymersome as versatile therapeutics codelivery nanovehicle for effective tumor suppression. Proc. Natl. Acad. Sci. U.S.A. 2019, 116, 7744–7749. Publisher's VersionAbstract

Effective cancer therapies often demand delivery of combinations of drugs to inhibit multidrug resistance through synergism, and the development of multifunctional nanovehicles with enhanced drug loading and delivery efficiency for combination therapy is currently a major challenge in nanotechnology. However, such combinations are more challenging to administer than single drugs and can require multipronged approaches to delivery. In addition to being stable and biodegradable, vehicles for such therapies must be compatible with both hydrophobic and hydrophilic drugs, and release drugs at sustained therapeutic levels. Here, we report synthesis of porous silicon nanoparticles conjugated with gold nanorods [composite nanoparticles (cNPs)] and encapsulate them within a hybrid polymersome using double-emulsion templates on a microfluidic chip to create a versatile nanovehicle. This nanovehicle has high loading capacities for both hydrophobic and hydrophilic drugs, and improves drug delivery efficiency by accumulating at the tumor after i.v. injection in mice. Importantly, a triple-drug combination suppresses breast tumors by 94% and 87% at total dosages of 5 and 2.5 mg/kg, respectively, through synergy. Moreover, the cNPs retain their photothermal properties, which can be used to significantly inhibit multidrug resistance upon near-infrared laser irradiation. Overall, this work shows that our nanovehicle has great potential as a drug codelivery nanoplatform for effective combination therapy that is adaptable to other cancer types and to molecular targets associated with disease progression.

Vahabikashi, A. ; Park, C. Y. ; Perkumas, K. ; Zhang, Z. ; Deurloo, E. K. ; Wu, H. ; Weitz, D. A. ; Stamer, W. D. ; Goldman, R. D. ; Fredberg, J. J. ; et al. Probe Sensitivity to Cortical versus Intracellular Cytoskeletal Network Stiffness. Biophys. J. 2019, 116, 518–529. Publisher's VersionAbstract

In development, wound healing, and pathology, cell biomechanical properties are increasingly recognized as being of central importance. To measure these properties, experimental probes of various types have been developed, but how each probe reflects the properties of heterogeneous cell regions has remained obscure. To better understand differences attributable to the probe technology, as well as to define the relative sensitivity of each probe to different cellular structures, here we took a comprehensive approach. We studied two cell types—Schlemm’s canal endothelial cells and mouse embryonic fibroblasts (MEFs)—using four different probe technologies: 1) atomic force microscopy (AFM) with sharp tip, 2) AFM with round tip, 3) optical magnetic twisting cytometry (OMTC), and 4) traction microscopy (TM). Perturbation of Schlemm’s canal cells with dexamethasone treatment, α-actinin overexpression, or RhoA overexpression caused increases in traction reported by TM and stiffness reported by sharp-tip AFM as compared to corresponding controls. By contrast, under these same experimental conditions, stiffness reported by round-tip AFM and by OMTC indicated little change. Knockout (KO) of vimentin in MEFs caused a diminution of traction reported by TM, as well as stiffness reported by sharp-tip and round-tip AFM. However, stiffness reported by OMTC in vimentin-KO MEFs was greater than in wild type. Finite-element analysis demonstrated that this paradoxical OMTC result in vimentin-KO MEFs could be attributed to reduced cell thickness. Our results also suggest that vimentin contributes not only to intracellular network stiffness but also cortex stiffness. Taken together, this evidence suggests that AFM sharp tip and TM emphasize properties of the actin-rich shell of the cell, whereas round-tip AFM and OMTC emphasize those of the noncortical intracellular network.

Cao, T. ; Wang, Y. ; Zhao, L. ; Wang, Y. ; Tao, Y. ; Heyman, J. A. ; Weitz, D. A. ; Zhou, Y. ; Zhang, X. A simple mix-and-read bacteria detection system based on DNAzyme and molecular beacon. Chem. Commun. 2019, 55, 7358-7361. Publisher's VersionAbstract

Here, we describe a simple mix-and-read method for the detection of specific bacterial strains that uses a DNAzyme and a molecular beacon to generate a signal. We have greatly improved upon the previously described DNAzyme-based bacteria detection method by eliminating a tedious preparation step while maintaining detection sensitivity.

Arriaga, L. R. ; Huang, Y. ; Kim, S. - H. ; Aragones, J. L. ; Ziblat, R. ; Koehler, S. A. ; Weitz, D. A. Single-step assembly of asymmetric vesicles. Lab Chip 2019, 19, 749–756. Publisher's VersionAbstract

Asymmetric vesicles are membranes in which amphiphiles are asymmetrically distributed between each membrane leaflet. This asymmetry dictates chemical and physical properties of these vesicles, enabling their use as more realistic models of biological cell membranes, which also are asymmetric, and improves their potential for drug delivery and cosmetic applications. However, their fabrication is difficult as the self-assembly of amphiphiles always leads to symmetric vesicles. Here, we report the use of water-in-oil-in-oil-in-water triple emulsion drops to direct the assembly of the two leaflets to form asymmetric vesicles. Different compositions of amphiphiles are dissolved in each of the two oil shells of the triple emulsion; the amphiphiles diffuse to the interfaces and adsorb differentially at each of the two oil/water interfaces of the triple emulsion. These middle oil phases dewet from the innermost water cores of the triple emulsion drops, leading to the formation of membranes with degrees of asymmetry up to 70%. The triple emulsion drops are fabricated using capillary microfluidics, enabling production of highly monodisperse drops at rates as high as 300 Hz. Vesicles produced by this method can very efficiently encapsulate many different ingredients; this further enhances the utility of asymmetric vesicles as artificial cells, bioreactors and delivery vehicles.

Michelon, M. ; Huang, Y. ; de la Torre, L. G. ; Weitz, D. A. ; Cunha, R. L. Single-step microfluidic production of W/O/W double emulsions as templates for β-carotene-loaded giant liposomes formation. Chemical Engineering Journal 2019, 366, 27–32. Publisher's VersionAbstract

We demonstrated the microfluidic production of W/O/W double emulsion droplets aiming formation of β-carotene-incorporated giant liposomes for food and/or pharmaceutical applications. For this purpose, glass-capillary microfluidic devices were fabricated to create a truly three-dimensional flow aiming production of giant unilamellar liposomes by solvent evaporation process after W/O/W double emulsion droplet templates formation. A great challenge of microfluidic production of monodisperse and stable W/O/W double emulsion templates for this proposal is the replacement of organic solvents potentially toxic for phospholipids dissolution. Besides, the high cost of several semi-synthetic phospholipids commonly used for giant liposome formation remains as a major technological challenge to be overcome. Thus, β-carotene-incorporated giant liposomes were generated using biocompatible solvents with low toxic potential (ethyl acetate and pentane) and non-purified soybean lecithin - a food-grade phospholipid mixture with low cost - by dewetting and evaporation of the solvents forming the oily intermediate phase of W/O/W double emulsion droplet templates. Our results showed monodisperse β-carotene-loaded giant liposomes with diameter ranging between 100 μm and 180 μm and a stability of approximately 7 days. In this way, a single-step microfluidic process with highly accurate control of size distribution was developed. This microfluidic process proposed is potentially useful for a broad range of applications in protection and delivery of active compounds.

Pei, H. ; Abbaspourrad, A. ; Zhang, W. ; Wu, Z. ; Weitz, D. A. Water-Triggered Rapid Release of Biocide with Enhanced Antimicrobial Activity in Biodiesel. Macromol. Mater. Eng. 2019, 304, 1900156. Publisher's VersionAbstract
Biodiesel inherently contains more water than mineral diesel and as a result microbial contamination is a major problem that hinders its widespread application. The current method of removing the microbial contamination is direct addition of biocide. However, this method cannot enrich the water phase with biocide rapidly enough, leading to unavoidable overdosing of biocide and environmental issues. Here, biocide is encapsulated within hydrogel microparticles with a water‐triggered release feature to improve antimicrobial efficiency of biocide in biodiesel. To demonstrate the water‐triggered release mechanism, a green dye is encapsulated within the microparticles. The encapsulated dye remains inside the microparticles for more than 6 weeks when the microparticles are stored in oil phase; however, the dye releases in 4 min when the microparticles contact water. Using this water‐triggered release strategy, biocide is successfully delivered to the water phase in biodiesel. The encapsulated biocide shows higher antimicrobial efficacy than that of free biocide, in both short‐term and long‐term experiments. The possibility of scaling up the production of hydrogel microparticles using bulk emulsification method is also explored. Moreover, the water‐triggered release strategy can be used for releasing other water‐soluble functional materials. This opens opportunities for a wide range of encapsulation and controlled delivery applications.
Kim, Q. H. ; Shin, D. ; Park, J. ; Weitz, D. A. ; Jhe, W. Initial growth dynamics of 10 nm nanobubbles in the graphene liquid cell. Appl. Nanosci. 2018. Publisher's VersionAbstract

The unexpected long lifetime of nanobubble against the large Laplace pressure is one of the important issues in nanobubble research and a few models have been proposed to explain it. Most studies, however, have been focused on the observation of relatively large nanobubbles over 100 nm and are limited to the equilibrium state phenomena. The study on the sub-100 nm sized nanobubble is still lacking due to the limitation of imaging methods which overcomes the optical resolution limit. Here, we demonstrate the observation of growth dynamics of 10 nm nanobubbles confined in the graphene liquid cell using transmission electron microscopy (TEM). We modified the classical diffusion theory by considering the finite size of the confined system of graphene liquid cell (GLC), successfully describing the temporal growth of nanobubble. Our study shows that the growth of nanobubble is determined by the gas oversaturation, which is affected by the size of GLC.

Li, Q. ; Zhang, Y. - W. ; Wang, C. - F. ; Weitz, D. A. ; Chen, S. Macroscopic Self-Assembly: Versatile Hydrogel Ensembles with Macroscopic Multidimensions (Adv. Mater. 52/2018). Adv. Mater. 2018, 30, 1870400. Publisher's VersionAbstract

A new microfluidic‐assisted self‐healing‐driven assembly strategy enabling continuous and controllable construction of programmed ordered assemblies is developed by Su Chen and co‐workers in article number 1803475. This allows self‐assembly to be carried out on the macroscopic scale toward tissue materials and light‐emitting diode devices.

Zhu, Z. ; Zhang, J. ; Tong, Y. -long; Peng, G. ; Cui, T. ; Wang, C. - F. ; Chen, S. ; Weitz, D. A. Reduced Graphene Oxide Membrane Induced Robust Structural Colors toward Personal Thermal Management. ACS Photonics 2018, 6 116-122. Publisher's VersionAbstract
Angle-independent structural colors are prepared by membrane separation-assisted assembly (MSAA) method with modified reduced graphene oxide (rGO) as the substrate membrane. We show that the wrinkled and crumpled rGO laminates not only ensure uneven morphology of colloidal film but improve color saturation by decreasing coherent scattering. In addition, we study the influence of stopband position on thermal insulation property of the colloidal film for the first time. High absolute temperature difference of 6.9 °C is achieved comparing with control sample. And films with longer stopband positions indicate better thermal insulation performance because of inherent slow photon effect in photonic structure. This general principle of thermal insulation by colloidal films opens the way to a new generation of thermal management materials.
Montessori, A. ; Lauricella, M. ; Stolovicki, E. ; Weitz, D. ; Succi, S. Topological aspects of jetting to dripping transition in step emulsifiers. Physics of Fluids 2018, 31, 021703. Publisher's VersionAbstract
Fully three-dimensional, time-dependent, direct simulations of the non-ideal Navier-Stokes equations for a two-component fluid shed light into the mechanism which inhibits droplet breakup in step emulsifiers below a critical threshold of the width-to-height (w/h) ratio of the microfluidic nozzle. Below w/h ∼ 2.6, the simulations provide evidence of a smooth topological transition of the fluid from the confined rectangular channel geometry to an isotropic (spherical) expansion of the fluid downstream the nozzle step. Above such threshold, the transition from the inner to the outer space involves a series of dynamical rearrangements which keep the free surface in mechanical balance. Such rearrangements also induce a backflow of the ambient fluid which, in turn, leads to jet pinching and ultimately to its rupture, namely, droplet formation. The simulations show remarkable agreement with the experimental value of the threshold, which is found around w/h ∼ 2.56.
Li, Q. ; Zhang, Y. - W. ; Wang, C. - F. ; Weitz, D. A. ; Chen, S. Versatile Hydrogel Ensembles with Macroscopic Multidimensions. Adv. Mater. 2018, 30, 1803475. Publisher's VersionAbstract
Methods allowing construction of macroscopic programmed materials in a flexible and efficient fashion are highly desirable. However, the existing approaches are far removed from such materials. A new self‐healing‐driven assembly (SHDA) strategy to fabricate various programmed materials by using uniform gel beads (microsize of 212 µm or millimeter size of 4 mm) as building blocks is described here. In virtue of hydrogen bonds and host–guest interactions between gel beads, a series of linear, planar, and 3D beaded assemblies are fabricated via SHDA in microfluidic channels in a continuous and controlled manner. From the perspective of practical applications, the use of gel assemblies is exploited for tissue engineering with controlled cells coculture, as well as light conversion materials toward white‐light‐emitting diodes (WLEDs). The SHDA strategy developed in this study gives a new insight into the facile and rapid fabrication of various programmed materials toward biological tissue and optoelectronic device.
Wang, H. - F. ; Ran, R. ; Liu, Y. ; Hui, Y. ; Zeng, B. ; Chen, D. ; Weitz, D. A. ; Zhao, C. - X. Tumor-Vasculature-on-a-Chip for Investigating Nanoparticle Extravasation and Tumor Accumulation. ACS Nano 2018, 12, 11600–11609. Publisher's VersionAbstract
Nanoparticle tumor accumulation relies on a key mechanism, the enhanced permeability and retention (EPR) effect, but it remains challenging to decipher the exact impact of the EPR effect. Animal models in combination with imaging modalities are useful, but it is impossible to delineate the roles of multiple biological barriers involved in nanoparticle tumor accumulation. Here we report a microfluidic tumor-vasculature-on-a-chip (TVOC) mimicking two key biological barriers, namely, tumor leaky vasculature and 3D tumor tissue with dense extracellular matrix (ECM), to study nanoparticle extravasation through leaky vasculature and the following accumulation in tumor tissues. Intact 3D tumor vasculature was developed with selective permeability of small molecules (20 kDa) but not large ones (70 kDa). The permeability was further tuned by cytokine stimulation, demonstrating the independent control of the leaky tumor vasculature. Combined with tumor spheroids in dense ECM, our TVOC model is capable of predicting nanoparticles’ in vivo tumor accumulation, thus providing a powerful platform for nanoparticle evaluation.
Ziblat, R. ; Weaver, J. ; Arriaga, L. R. ; Chong, S. ; Weitz, D. A. Determining the Lipid Specificity of Insoluble Protein Transmembrane Domains. Lab Chip 2018, 18, 3561-3569. Publisher's VersionAbstract
While the specificity of protein–lipid interactions is a key feature in the function of biological membranes, studying the specifics of these interactions is challenging because most membrane proteins are insoluble in water due to the hydrophobic nature of their transmembrane domains (TMDs). Here, we introduce a method that overcomes this solubility limitation and identifies the affinity profile of protein TMDs to specific lipid formulations. Using 5 human TMDs as a sample group, our results demonstrate that TMDs are highly selective and that these specific lipid–TMD interactions can involve either a single lipid, or the combination of multiple lipid species.
Shi, W. ; Didier, J. E. ; Ingber, D. E. ; Weitz, D. A. Collective Shape Actuation of Polymer Double Emulsions by Solvent Evaporation. ACS Applied Materials & Interfaces 2018, 10, 31865–31869. Publisher's VersionAbstract
We demonstrate that the shape actuation of waterin-oil-in-water double emulsion droplets can be achieved by controlling solvent evaporation in a model system, where the oil phase consists of hydrophobic homopolymer/amphiphilic block copolymer/solvent. A gradient of interfacial tension is created in the polymer shell, which drives significant deformation of the droplets in constant volume. The deformed droplets recover to their initial shape spontaneously, and shape actuation of droplets can be further tuned by osmotic pressure. Our model system provides a new prototype for developing shape-responsive droplets in a solvent environment.