Du, J. S. ; Park, J. ; Kim, Q. H. ; Jhe, W. ; Dravid, V. P. ; Yang, D. ; Weitz, D. A. Multistage Transformation and Lattice Fluctuation at AgCl–Ag Interface. J. Phys. Chem. Lett. 2017, 8 5853–5860. Publisher's VersionAbstract
Solid-state transformation between different materials is often accompanied by mechanical expansion and compression due to their volume change and structural evolution at interfaces. However, these two types of dynamics are usually difficult to monitor in the same time. In this work, we use in situ transmission electron microscopy to directly study the reduction transformation at the AgCl–Ag interface. Three stages of lattice fluctuations were identified and correlated to the structural evolution. During the steady state, a quasi-layered growth mode of Ag in both vertical and lateral directions were observed due to the confinement of AgCl lattices. The development of planar defects and depletion of AgCl are respectively associated with lattice compression and relaxation. Topography and structure of decomposing AgCl was further monitored by in situ scanning transmission electron microscopy. Silver species are suggested to originate from both the surface and the interior of AgCl, and be transported to the interface. Such mass transport may have enabled the steady state and lattice compression in this volume-shrinking transformation.
Wang, L. ; Chen, D. ; Gutierrez-Cuevas, K. G. ; Bisoyi, H. K. ; Fan, J. ; Zola, R. S. ; Li, G. ; Urbas, A. M. ; Bunning, T. J. ; Weitz, D. A. ; et al. Optically reconfigurable chiral microspheres of self-organized helical superstructures with handedness inversion. Mater. Horiz. 2017, 4 1190–1195. Publisher's VersionAbstract
Optically reconfigurable monodisperse chiral microspheres of self-organized helical superstructures with dynamic chirality were fabricated via a capillary-based microfluidic technique. Light-driven handedness-invertible transformations between different configurations of microspheres were vividly observed and optically tunable RGB photonic cross-communications among the microspheres were demonstrated.
Weitz, D. A. Perspective on droplet-based single-cell sequencing. Lab Chip 2017, 17, 2539. Publisher's Version weitz2017.pdf
Shi, W. ; Weitz, D. A. Polymer Phase Separation in a Microcapsule Shell. Macromolecules 2017, 50, 7681–7686. Publisher's VersionAbstract
Phase separation has been used for engineering microscale fluids and particles with designed structures. But it is challenging to use phase separation to create complicated microcapsules because phase separation in the shell correlates with applied osmotic pressure and affects capsule stability significantly. Here we employ two biodegradable polymers to study the phase separation in microcapsule shells and its effect on the mechanical stability. The dynamic process reveals that phase separation creates a patchy shell with distinct regions transiently, then transports the discrete domains across the shell, and coalesces them at the surface. The equilibrium structure with balanced osmotic pressure is a Janus shell, where one component forms the shell and the other component dewets on the surface. Under slight osmotic pressure to the shell, phase separation reaches a different Janus shape, which consists of two partial shells of each component. We can in further take advantage of phase separation and osmotic pressure to rupture microcapsules at specific locations. Phase separation in the shell provides a facile approach to create versatile capsule structures and affords a reliable strategy to harness the shell mechanics.
Egan, P. F. ; Moore, J. R. ; Ehrlicher, A. J. ; Weitz, D. A. ; Schunn, C. ; Cagan, J. ; LeDuc, P. Robust mechanobiological behavior emerges in heterogeneous myosin systems. Proc. Natl. Acad. Sci. U.S.A. 2017, 114, E8147-E8154. Publisher's VersionAbstract
Biological complexity presents challenges for understanding natural phenomenon and engineering new technologies, particularly in systems with molecular heterogeneity. Such complexity is present in myosin motor protein systems, and computational modeling is essential for determining how collective myosin interactions produce emergent system behavior. We develop a computational approach for altering myosin isoform parameters and their collective organization, and support predictions with in vitro experiments of motility assays with α-actinins as molecular force sensors. The computational approach models variations in single myosin molecular structure, system organization, and force stimuli to predict system behavior for filament velocity, energy consumption, and robustness. Robustness is the range of forces where a filament is expected to have continuous velocity and depends on used myosin system energy. Myosin systems are shown to have highly nonlinear behavior across force conditions that may be exploited at a systems level by combining slow and fast myosin isoforms heterogeneously. Results suggest some heterogeneous systems have lower energy use near stall conditions and greater energy consumption when unloaded, therefore promoting robustness. These heterogeneous system capabilities are unique in comparison with homogenous systems and potentially advantageous for high performance bionanotechnologies. Findings open doors at the intersections of mechanics and biology, particularly for understanding and treating myosin-related diseases and developing approaches for motor molecule-based technologies.
Alim, K. ; Parsa, S. ; Weitz, D. A. ; Brenner, M. P. Local Pore Size Correlations Determine Flow Distributions in Porous Media. Physical Review Letters 2017, 119, 144501. Publisher's VersionAbstract
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.
Zhang, H. ; Qu, X. ; Chen, H. ; Kong, H. ; Ding, R. ; Chen, D. ; Zhang, X. ; Pei, H. ; Santos, H. A. ; Hai, M. ; et al. Fabrication of Calcium Phosphate-Based Nanocomposites Incorporating DNA Origami, Gold Nanorods, and Anticancer drugs for Biomedical Applications. Advanced Healthcare Materials 2017, 6 1700664. Publisher's VersionAbstract
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.
Wu, J. ; Cai, L. - H. ; Weitz, D. A. Tough Self-Healing Elastomers by Molecular Enforced Integration of Covalent and Reversible Networks. Advanced Materials 2017, 29, 1702616. Publisher's VersionAbstract
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.
Pegoraro, A. F. ; Janmey, P. ; Weitz, D. A. Mechanical Properties of the Cytoskeleton and Cells. Cold Spring Harbor-Perspectives in Biology 2017, 9 1-12. Publisher's VersionAbstract

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.

Ung, W. L. ; Mutafopulos, K. ; Spink, P. ; Rambach, R. W. ; Franke, T. ; Weitz, D. A. Enhanced Surface Acoustic Wave Cell Sorting by 3D Microfluidic-Chip Design. Lab on a Chip 2017, 17, 4059-4069. Publisher's VersionAbstract
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.
Chaudhuri, M. ; Allahyarov, E. ; Löwen, H. ; Egelhaaf, S. U. ; Weitz, D. A. Triple Junction at the Triple Point Resolved on the Individual Particle Level. Phys. Rev. Lett. 2017, 119, 128001. Publisher's VersionAbstract

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.

    Zhao, C. - X. ; Chen, D. ; Hui, Y. ; Weitz, D. A. ; Middelberg, A. P. J. Controlled Generation of Ultrathin-Shell Double Emulsions and Studies on Their Stability. ChemPhysChem 2017, 18, 1393–1399. Publisher's VersionAbstract
    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.
    Beroz, F. ; Jawerth, L. M. ; Münster, S. ; Weitz, D. A. ; Broedersz, C. P. ; Wingreen, N. S. Physical limits to biomechanical sensing in disordered fibre networks. Nature communications 2017, 8 16096. Publisher's VersionAbstract

    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.

    Kong, L. ; Amstad, E. ; Hai, M. ; Ke, X. ; Chen, D. ; Zhao, C. - X. ; Weitz, D. A. Biocompatible microcapsules with a water core templated from single emulsions. Chinese Chemical Letters 2017, 28, 1897-1900. Publisher's VersionAbstract

    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.

    Fan, J. ; Kim, S. - H. ; Chen, Z. ; Zhou, S. ; Amstad, E. ; Lin, T. ; Weitz, D. A. Creation of Faceted Polyhedral Microgels from Compressed Emulsions. Small 2017, 13, 1701256. Publisher's VersionAbstract
    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.
    Zhang, W. ; Abbaspourrad, A. ; Chen, D. ; Campbell, E. ; Zhao, H. ; Li, Y. ; Li, Q. ; Weitz, D. A. Osmotic Pressure Triggered Rapid Release of Encapsulated Enzymes with Enhanced Activity. Advanced Functional Materials 2017, 27, 1700975. Publisher's VersionAbstract
    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.
    Amstad, E. ; Chen, X. ; Eggersdorfer, M. ; Cohen, N. ; Kodger, T. E. ; Ren, C. L. ; Weitz, D. A. Parallelization of microfluidic flow-focusing devices. Physical Review E 2017, 95, 043105. Publisher's VersionAbstract

    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.

      Kodger, T. E. ; Lu, P. J. ; Wiseman, G. R. ; Weitz, D. A. Stable, fluorescent PMMA particles for long-term observation of slow colloidal dynamics. Langmuir 2017, 33, 6382–6389. Publisher's VersionAbstract

      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.

      Haliburton, J. R. ; Kim, S. C. ; Clark, I. C. ; Sperling, R. A. ; Weitz, D. A. ; Abate, A. R. Efficient extraction of oil from droplet microfluidic emulsions. Biomicrofluidics 2017, 11, 034111. Publisher's VersionAbstract

      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.

      Prakadan, S. M. ; Shalek, A. K. ; Weitz, D. A. Scaling by shrinking: empowering single-cell'omics' with microfluidic devices. Nature Reviews Genetics 2017, 18, 345–361. Publisher's VersionAbstract

      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.