Zhou, S. ; Fan, J. ; Datta, S. S. ; Guo, M. ; Guo, X. ; Weitz, D. A. Thermally switched release from nanoparticle colloidosomes. Advanced Functional Materials 2013, 23, 5925-5929.Abstract

Nanoparticle colloidosomes, whose release can be switched on and off in response to a temperature change, are fabricated. Unlike in other systems, the switchable release does not require the colloidosome shell to deform; it instead occurs due to the adsorption or desorption of a block copolymer, dissolved in the core, at the inner surface of the colloidosome shell, concomitantly blocking or unblocking the pores in the shell. The colloidosomes are prepared using double emulsion templates produced by microfluidics, and are thus highly monodisperse; moreover, they are mechanically stable and consist of biocompatible components, making them suitable for the encapsulation, delivery, and release of a broad range of active materials.

Abbaspourrad, A. ; Carroll, N. J. ; Kim, S. - H. ; Weitz, D. A. Polymer microcapsules with programmable active release. Journal of the American Chemical Society 2013, 135, 7744-7750.Abstract

We present a new type of microcapsule programmed with a tunable active release mechanism. The capsules are triggered by a plasticizing stimulus that induces a phase change transition of the polymeric membrane from a solid to a fluidized form; thereafter, the cargo is actively driven out of the capsule through a defect at the capsule wall with controllable release kinetics. Tuning the degree of membrane fluidity by tailoring the amount of plasticizing stimulus present allows us to obtain temporal variation of the release kinetics from a subsecond abrupt burst release to a slow sustained release of encapsulant over many minutes. Moreover, we demonstrate tuning of the collective capsule triggering response by adjusting stimulus content, polymer molecular weight, and capsule membrane thickness. For this model system, we use a microfluidic approach to fabricate polystyrene capsules triggered by a toluene stimulus. However, this active release approach is general and is applicable to diverse polymeric capsule systems; this versatility is demonstrated by extension of our trigger-release scheme to capsules fabricated from a rubberlike block copolymer. The utility of our technique further enhances the potential of these active release capsules for practical application.

van Steijn, V. ; Korczyk, P. M. ; Derzsi, L. ; Abate, A. R. ; Weitz, D. A. ; Garstecki, P. Block-and-break generation of microdroplets with fixed volume. Biomicrofluidics 2013, 7.Abstract

We introduce a novel type of droplet generator that produces droplets of a volume set by the geometry of the droplet generator and not by the flow rates of the liquids. The generator consists of a classic T-junction with a bypass channel. This bypass directs the continuous fluid around the forming droplets, so that they can fill the space between the inlet of the dispersed phase and the exit of the bypass without breaking. Once filled, the dispersed phase blocks the exit of the bypass and is squeezed by the continuous fluid and broken off from the junction. We demonstrate the fixed-volume droplet generator for (i) the formation of monodisperse droplets from a source of varying flow rates, (ii) the formation of monodisperse droplets containing a gradation of solute concentration, and (iii) the parallel production of monodisperse droplets. (C) 2013 AIP Publishing LLC. []

Zidovska, A. ; Weitz, D. A. ; Mitchison, T. J. Micron-scale coherence in interphase chromatin dynamics. Proceedings of the National Academy of Sciences of the United States of America 2013, 110, 15555-15560.Abstract

Chromatin structure and dynamics control all aspects of DNA biology yet are poorly understood, especially at large length scales. We developed an approach, displacement correlation spectroscopy based on time-resolved image correlation analysis, to map chromatin dynamics simultaneously across the whole nucleus in cultured human cells. This method revealed that chromatin movement was coherent across large regions (4-5 mu m) for several seconds. Regions of coherent motion extended beyond the boundaries of single-chromosome territories, suggesting elastic coupling of motion over length scales much larger than those of genes. These large-scale, coupled motions were ATP dependent and unidirectional for several seconds, perhaps accounting for ATP-dependent directed movement of single genes. Perturbation of major nuclear ATPases such as DNA polymerase, RNA polymerase II, and topoisomerase II eliminated micron-scale coherence, while causing rapid, local movement to increase; i.e., local motions accelerated but became uncoupled from their neighbors. We observe similar trends in chromatin dynamics upon inducing a direct DNA damage; thus we hypothesize that this may be due to DNA damage responses that physically relax chromatin and block long-distance communication of forces.

Lu, P. J. ; Weitz, D. A. ; Langer, J. S. Colloidal particles: Crystals, glasses, and gels. In Annual Review of Condensed Matter Physics, Vol 4; 2013; Vol. 4, pp. 217-233.Abstract

Colloidal particles are microscopic solid particles suspended in a fluid. Colloids are small enough that thermal energy drives their dynamics and ensures equilibration with the suspending fluid; they are also large enough that their positions and motions can be measured precisely using optical methods, such as light scattering and laser-scanning confocal fluorescence microscopy. Colloidal suspensions are a powerful model system for the study of other phenomena in condensed matter physics, where the collective phase behavior of the solid particles mimics that of other condensed systems. We review three classes of interacting colloidal particles, crystals, glasses, and gels, each of which represents fascinating properties of colloidal particles as well as a model for more general types of materials and their behavior.

Jensen, K. E. ; Pennachio, D. ; Recht, D. ; Weitz, D. A. ; Spaepen, F. Rapid growth of large, defect-free colloidal crystals. Soft Matter 2013, 9 320-328.Abstract

We demonstrate controlled growth of face-centered cubic (FCC), monodisperse hard-sphere colloidal crystals by centrifugation at up to 3000g onto FCC (100) templates. Such rapid deposition rates often result in an amorphous sediment. Surprisingly, however, growth onto (100) templates results only in single crystals with few or no extended defects. By contrast, deposition onto flat, (111), or (110) templates causes rapid disordering to an amorphous sediment if the dimensionless flux (particle volume fraction x Peclet number) exceeds a critical value. This crystalline-to-amorphous crossover results from the degeneracy of possible stacking positions for these orientations. No such degeneracy exists for growth onto (100). After growth, extended defects can nucleate and grow only if the crystal exceeds a critical thickness that depends on the lattice misfit with the template spacing. The experimental observations of the density of misfit dislocations are accounted for by the Frank-van der Merwe theory, adapted for the depth-dependent variation of lattice spacing and elastic constants that results from the gravitational pressure.

Yao, N. Y. ; Broedersz, C. P. ; Depken, M. ; Becker, D. J. ; Pollak, M. R. ; MacKintosh, F. C. ; Weitz, D. A. Stress-enhanced gelation: A dynamic nonlinearity of elasticity. Physical Review Letters 2013, 110.Abstract

A hallmark of biopolymer networks is their sensitivity to stress, reflected by pronounced nonlinear elastic stiffening. Here, we demonstrate a distinct dynamical nonlinearity in biopolymer networks consisting of filamentous actin cross-linked by alpha-actinin-4. Applied stress delays the onset of relaxation and flow, markedly enhancing gelation and extending the regime of solidlike behavior to much lower frequencies. We show that this macroscopic network response can be accounted for at the single molecule level by the increased binding affinity of the cross-linker under load, characteristic of catch-bond-like behavior. DOI: 10.1103/PhysRevLett.110.018103

Datta, S. S. ; Weitz, D. A. Drainage in a model stratified porous medium. Epl 2013, 101.Abstract

We show that when a non-wetting fluid drains a stratified porous medium at sufficiently small capillary numbers Ca, it flows only through the coarsest stratum of the medium; by contrast, above a threshold Ca, the non-wetting fluid is also forced laterally, into part of the adjacent, finer strata. The spatial extent of this partial invasion increases with Ca. We quantitatively understand this behavior by balancing the stratum-scale viscous pressure driving the flow with the capillary pressure required to invade individual pores. Because geological formations are frequently stratified, we anticipate that our results will be relevant to a number of important applications, including understanding oil migration, preventing groundwater contamination, and sub-surface CO2 storage. Copyright (C) EPLA, 2013

Lin, T. ; Kodger, T. E. ; Weitz, D. A. Transport of charged colloids in a nonpolar solvent. Soft Matter 2013, 9 5173-5177.Abstract

In nonpolar solvents, surfactants stabilize charge through the formation of reverse micelles; this enables the dissociation of charge from the surfaces of particles, thereby charge-stabilizing particle suspensions. We investigate the dynamics of such charged particles by directly visualizing their motion across a microfluidic channel in response to an external electric field. The presence of the reverse micelles has a significant effect on particle motion: in a constant field, the particles initially move, then slow down exponentially, and eventually stop. This is due to the accumulation of reverse micelles at the channel walls, which screens the applied field, leading to the subsequent decay of the internal electric field. The time constant of decay depends on the electrical conductivity of the particle suspension and the width of the channel; this behavior is modeled as an equivalent RC circuit.

Jensen, K. E. ; Weitz, D. A. ; Spaepen, F. A three-dimensional calibration device for the confocal microscope. Review of Scientific Instruments 2013, 84.Abstract

Modern confocal microscopes enable high-precision measurement in three dimensions by collecting stacks of 2D (x-y) images that can be assembled digitally into a 3D image. It is difficult, however, to ensure position accuracy, particularly along the optical (z) axis where scanning is performed by a different physical mechanism than in x-y. We describe a simple device to calibrate simultaneously the x, y, and z pixel-to-micrometer conversion factors for a confocal microscope. By taking a known 2D pattern and positioning it at a precise angle with respect to the microscope axes, we created a 3D reference standard. The device is straightforward to construct and easy to use. (C) 2013 American Institute of Physics. []

Windbergs, M. ; Zhao, Y. ; Heyman, J. ; Weitz, D. A. Biodegradable core-shell carriers for simultaneous encapsulation of synergistic actives. Journal of the American Chemical Society 2013, 135, 7933-7937.Abstract

Simultaneous encapsulation of multiple active substances in a single carrier is essential for therapeutic applications of synergistic combinations of drugs. However, traditional carrier systems often lack efficient encapsulation and release of incorporated substances, particularly when combinations of drugs must be released in concentrations of a prescribed ratio. We present a novel biodegradable core shell carrier system fabricated in a one-step, solvent-free process on a microfluidic chip; a hydrophilic active (doxorubicin hydrochloride) is encapsulated in the aqueous core, while a hydrophobic active (paclitaxel) is encapsulated in the solid shell. Particle size and composition can be precisely controlled, and core and shell can be individually loaded with very high efficiency. Drug-loaded particles can be dried and stored as a powder. We demonstrate the efficacy of this system through the simultaneous encapsulation and controlled release of two synergistic anticancer drugs using two cancer-derived value for encapsulation of other active cell lines. This solvent-free platform technology is also of high potential ingredients and chemical reagents.

Abbaspourrad, A. ; Datta, S. S. ; Weitz, D. A. Controlling release from pH-responsive microcapsules. Langmuir 2013, 29, 12697-12702.Abstract

We report a microfluidic approach to produce monodisperse pH-responsive microcapsules with precisely controlled release behavior. The solid microcapsule shells are composed of a biocompatible pH-responsive polymer and robustly encapsulate an active material; however, when exposed to a trigger pH, the shells degrade and ultimately release the microcapsule contents. We control the trigger pH by using polymers that dissolve at different pH values. We independently control the time at which the microcapsule contents are released by carefully controlling the shell thickness. Moreover, we independently control the rate at which the encapsulated contents are released by making hybrid shells composed of a mixture of a pH-responsive polymer and varying proportions of another, solid, pH-unresponsive polymer. This enables us to achieve monodisperse microcapsules that robustly encapsulate an active material, only releasing it when exposed to a desired pH, after a prescribed time delay, and at a prescribed rate.

Abate, A. R. ; Hung, T. ; Sperling, R. A. ; Mary, P. ; Rotem, A. ; Agresti, J. J. ; Weiner, M. A. ; Weitz, D. A. DNA sequence analysis with droplet-based microfluidics. Lab on a Chip 2013, 13, 4864-4869.Abstract

Droplet-based microfluidic techniques can form and process micrometer scale droplets at thousands per second. Each droplet can house an individual biochemical reaction, allowing millions of reactions to be performed in minutes with small amounts of total reagent. This versatile approach has been used for engineering enzymes, quantifying concentrations of DNA in solution, and screening protein crystallization conditions. Here, we use it to read the sequences of DNA molecules with a FRET-based assay. Using probes of different sequences, we interrogate a target DNA molecule for polymorphisms. With a larger probe set, additional polymorphisms can be interrogated as well as targets of arbitrary sequence.

Kim, S. - H. ; Kim, J. W. ; Kim, D. - H. ; Han, S. - H. ; Weitz, D. A. Enhanced-throughput production of polymersomes using a parallelized capillary microfluidic device. Microfluidics and Nanofluidics 2013, 14, 509-514.Abstract

We report a parallelized capillary microfluidic device for enhanced production rate of monodisperse polymersomes. This device consists of four independent capillary microfluidic devices, operated in parallel; each device produces monodisperse water-in-oil-in-water (W/O/W) double-emulsion drops through a single-step emulsification. During generation of the double-emulsion drops, the innermost water drop is formed first and it triggers a breakup of the middle oil phase over wide range of flow rates; this enables robust and stable formation of the double-emulsion drops in all drop makers of the parallelized device. Double-emulsion drops are transformed to polymersomes through a dewetting of the amphiphile-laden middle oil phase on the surface of the innermost water drop, followed by the subsequent separation of the oil drop. Therefore, we can make polymersomes with a production rate enhanced by a factor given by the number of drop makers in the parallelized device.

Rodriguez-Lopez, J. ; Shum, H. C. ; Elvira, L. ; Montero de Espinosa, F. ; Weitz, D. A. Fabrication and manipulation of polymeric magnetic particles with magnetorheological fluid. Journal of Magnetism and Magnetic Materials 2013, 326, 220-224.Abstract

Polymeric magnetic microparticles have been created using a microfluidic device via ultraviolet (UV) polymerization of double emulsions, resulting in cores of magnetorheological (MR) fluids surrounded by polymeric shells. We demonstrate that the resultant particles can be manipulated magnetically to achieve triggered rupture of the capsules. This illustrates the great potential of our capsules for triggered release of active ingredients encapsulated in the polymeric magnetic microparticles. (C) 2012 Elsevier BY. All rights reserved.

Lee, J. Y. ; Hwang, J. W. ; Jung, H. W. ; Kim, S. H. ; Lee, S. J. ; Yoon, K. ; Weitz, D. A. Fast dynamics and relaxation of colloidal drops during the drying process using multispeckle diffusing wave spectroscopy. Langmuir 2013, 29, 861-866.Abstract

The fast dynamics generated by the Brownian motion of particles in colloidal drops, and the related relaxation during drying, which play key roles in suspension systems, were investigated incorporating multispeckle diffusing wave spectroscopy (MSDWS). MSDWS equipment was implemented to analyze the relaxation properties of suspensions under a nonergodic and nonstationary drying process, which cannot be elucidated by conventional light scattering methods, such as dynamic light scattering and diffusing wave spectroscopy. Rapid particle movement can be identified by the characteristic relaxation time, which is closely related to the Brownian motion due to thermal fluctuations of the particles. In the compacting stage of the drying process, the characteristic relaxation time increased gradually with the drying time because the particles in the colloidal drop were constrained by themselves. Moreover, variations of the initial concentration and particle size considerably affected the complete drying time and characteristic relaxation time, producing a shorter relaxation time for a low concentrated suspension with small particles.

Kim, S. - H. ; Nam, J. ; Kim, J. W. ; Kim, D. - H. ; Han, S. - H. ; Weitz, D. A. Formation of polymersomes with double bilayers templated by quadruple emulsions. Lab on a Chip 2013, 13, 1351-1356.Abstract

Polymersomes, vesicles composed of bilayer membranes of amphiphilic block-copolymers, are promising delivery vehicles for long-term storage and controlled release of bioactives; enhanced stability of the membrane makes polymersomes potentially useful in a wide range of biological delivery applications by comparison with liposomes. However, unilamellar structure is intrinsically fragile when subjected to external stress. Here, we report a microfluidic approach to produce polymersomes with double bilayers, providing higher stability and lower permeability than unilamellar polymersomes. To achieve this, we developed a new design of a capillary microfluidic device to produce quadruple-emulsion drops which serve as a template for the polymersomes-in-polymersomes. When two bilayers are attracted by depletion in polymersomes-in-polymersomes, the inner polymersomes protrude and bud, forming double bilayers. We confirm these structures are indeed double bilayers using microaspiration and selective doping of the leaflets with nanoparticles. The resultant polymersomes have great potential as highly stable and biocompatible microcarriers for robust encapsulation and storage of bioactives such as drugs, cosmetics and nutrients.

Chen, H. ; Li, J. ; Wan, J. ; Weitz, D. A. ; Stone, H. A. Gas-core triple emulsions for ultrasound triggered release. Soft Matter 2013, 9 38-42.Abstract

Gas-in-oil-in-water-in-oil triple emulsions are fabricated with a microfluidic method. The encapsulating layers can be triggered for release by ultrasound, owing to the gas core. Due to the stability in the atmosphere, the emulsions are polymerized by using UV light outside the device to fabricate compound particles with a gas-in-liquid-in-solid structure.

Wang, W. ; Zhang, M. - J. ; Xie, R. ; Ju, X. - J. ; Yang, C. ; Mou, C. - L. ; Weitz, D. A. ; Chu, L. - Y. Hole-shell microparticles from controllably evolved double emulsions. Angewandte Chemie-International Edition 2013, 52, 8084-8087. [PDF]
Wilking, J. N. ; Zaburdaev, V. ; De Volder, M. ; Losick, R. ; Brenner, M. P. ; Weitz, D. A. Liquid transport facilitated by channels in Bacillus subtilis biofilms. Proceedings of the National Academy of Sciences of the United States of America 2013, 110, 848-852.Abstract

Many bacteria on earth exist in surface-attached communities known as biofilms. These films are responsible for manifold problems, including hospital-acquired infections and biofouling, but they can also be beneficial. Biofilm growth depends on the transport of nutrients and waste, for which diffusion is thought to be the main source of transport. However, diffusion is ineffective for transport over large distances and thus should limit growth. Nevertheless, biofilms can grow to be very large. Here we report the presence of a remarkable network of well-defined channels that form in wildtype Bacillus subtilis biofilms and provide a system for enhanced transport. We observe that these channels have high permeability to liquid flow and facilitate the transport of liquid through the biofilm. In addition, we find that spatial variations in evaporative flux from the surface of these biofilms provide a driving force for the flow of liquid in the channels. These channels offer a remarkably simple system for liquid transport, and their discovery provides insight into the physiology and growth of biofilms.