Publications

2015
Bannwarth, M. B. ; Utech, S. ; Ebert, S. ; Weitz, D. A. ; Crespy, D. ; Landfester, K. Colloidal Polymers with Controlled Sequence and Branching Constructed from Magnetic Field Assembled Nanoparticles. ACS Nano 2015, 9 2720-2728. Publisher's VersionAbstract

The assembly of nanoparticles into polymer-like architectures is challenging and usually requires highly defined colloidal building blocks. Here, we show that the broad size-distribution of a simple dispersion of magnetic nanocolloids can be exploited to obtain various polymer-like architectures. The particles are assembled under an external magnetic field and permanently linked by thermal sintering. The remarkable variety of polymer–analogue architectures that arises from this simple process ranges from statistical and block copolymer-like sequencing to branched chains and networks. This library of architectures can be realized by controlling the sequencing of the particles and the junction points via a size-dependent self-assembly of the single building blocks.

2015_acsnano_bannwarth.pdf
Kanai, T. ; Boon, N. ; Lu, P. J. ; Sloutskin, E. ; Schofield, A. B. ; Smallenburg, F. ; van Roij, R. ; Dijkstra, M. ; Weitz, D. A. Crystallization and reentrant melting of charged colloids in nonpolar solvents. Phys. Rev. E 2015, 91, 030301. Publisher's VersionAbstract

We explore the crystallization of charged colloidal particles in a nonpolar solvent mixture. We simultaneously charge the particles and add counterions to the solution with aerosol-OT (AOT) reverse micelles. At low AOT concentrations, the charged particles crystallize into body-centered-cubic (bcc) or face-centered-cubic (fcc) Wigner crystals; at high AOT concentrations, the increased screening drives a thus far unobserved reentrant melting transition. We observe an unexpected scaling of the data with particle size, and account for all behavior with a model that quantitatively predicts both the reentrant melting and the data collapse.

    2015_pre_kanai.pdf
    Lee, W. C. ; Kim, K. ; Park, J. ; Koo, J. ; Jeong, H. Y. ; Lee, H. ; Weitz, D. A. ; Zettl, A. ; Takeuchi, S. Graphene-templated directional growth of an inorganic nanowire. Nature Nanotechnology 2015, 10, 423-428. Publisher's VersionAbstract

    Assembling inorganic nanomaterials on graphene is of interest in the development of nanodevices and nanocomposite materials, and the ability to align such inorganic nanomaterials on the graphene surface is expected to lead to improved functionalities, as has previously been demonstrated with organic nanomaterials epitaxially aligned on graphitic surfaces. However, because graphene is chemically inert, it is difficult to precisely assemble inorganic nanomaterials on pristine graphene. Previous techniques based on dangling bonds of damaged graphene, intermediate seed materials and vapour-phase deposition at high temperature have only formed randomly oriented or poorly aligned inorganic nanostructures. Here, we show that inorganic nanowires of gold(I) cyanide can grow directly on pristine graphene, aligning themselves with the zigzag lattice directions of the graphene. The nanowires are synthesized through a self-organized growth process in aqueous solution at room temperature, which indicates that the inorganic material spontaneously binds to the pristine graphene surface. First-principles calculations suggest that this assembly originates from lattice matching and π interaction to gold atoms. Using the synthesized nanowires as templates, we also fabricate nanostructures with controlled crystal orientations such as graphene nanoribbons with zigzag-edged directions.

    lee2015.pdf
    Fischer, A. E. ; Wu, S. K. ; Proescher, J. B. G. ; Rotem, A. ; Chang, C. B. ; Zhang, H. ; Tao, Y. ; Mehoke, T. S. ; Thielen, P. M. ; Kolawole, A. O. ; et al. A high-throughput drop microfluidic system for virus culture and analysis. Journal of Virological Methods 2015, 213, 111-117. Publisher's VersionAbstract

    High mutation rates and short replication times lead to rapid evolution in RNA viruses. New tools for high-throughput culture and analysis of viral phenotypes will enable more effective studies of viral evolutionary processes. A water-in-oil drop microfluidic system to study virus–cell interactions at the single event level on a massively parallel scale is described here. Murine norovirus (MNV-1) particles were co-encapsulated with individual RAW 264.7 cells in 65 pL aqueous drops formed by flow focusing in 50 μm microchannels. At low multiplicity of infection (MOI), viral titers increased greatly, reaching a maximum 18 h post-encapsulation. This system was employed to evaluate MNV-1 escape from a neutralizing monoclonal antibody (clone A6.2). Further, the system was validated as a means for testing escape from antibody neutralization using a series of viral point mutants. Finally, the replicative capacity of single viral particles in drops under antibody stress was tested. Under standard conditions, many RNA virus stocks harbor minority populations of genotypic and phenotypic variants, resulting in quasispecies. These data show that when single cells are encapsulated with single viral particles under antibody stress without competition from other virions, the number of resulting infectious particles is nearly equivalent to the number of viral genomes present. These findings suggest that lower fitness virions can infect cells successfully and replicate, indicating that the microfluidics system may serve as an effective tool for isolating mutants that escape evolutionary stressors.

    fischer2015.pdf
    Köster, S. ; Weitz, D. A. ; Goldman, R. D. ; Aebi, U. ; Herrmann, H. Intermediate filament mechanics in vitro and in the cell: from coiled coils to filaments, fibers and networks. Current Opinion in Cell Biology 2015, 32, 82-91. Publisher's VersionAbstract

    Intermediate filament proteins form filaments, fibers and networks both in the cytoplasm and the nucleus of metazoan cells. Their general structural building plan accommodates highly varying amino acid sequences to yield extended dimeric α-helical coiled coils of highly conserved design. These ‘rod’ particles are the basic building blocks of intrinsically flexible, filamentous structures that are able to resist high mechanical stresses, that is, bending and stretching to a considerable degree, both in vitro and in the cell. Biophysical and computer modeling studies are beginning to unfold detailed structural and mechanical insights into these major supramolecular assemblies of cell architecture, not only in the ‘test tube’ but also in the cellular and tissue context.

    koster2015.pdf
    Jensen, M. H. ; Morris, E. J. ; Goldman, R. D. ; Weitz, D. A. Emergent properties of composite semiflexible biopolymer networks. BioArchitecture 2015, 4 138-143. Publisher's VersionAbstract

    The semiflexible polymers filamentous actin (F-actin) and intermediate filaments (IF) both form complex networks within the cell, and together are key determinants of cellular stiffness. While the mechanics of F-actin networks together with stiff microtubules have been characterized, the interplay between F-actin and IF networks is largely unknown, necessitating the study of composite networks using mixtures of semiflexible biopolymers. We employ bulk rheology in a simplified in vitro system to uncover the fundamental mechanical interactions between networks of the 2 semiflexible polymers, F-actin and vimentin IF. Surprisingly, co-polymerization of actin and vimentin can produce composite networks either stronger or weaker than pure F-actin networks. We show that this effect occurs through steric constraints imposed by IF on F-actin during network formation and filament crosslinking, highlighting novel emergent behavior in composite semiflexible networks.

    jensen2015.pdf

    [*Equal contribution]

    Zieringer, M. A. ; Carroll, N. J. ; Abbaspourrad, A. ; Koehler, S. A. ; Weitz, D. A. Microcapsules for Enhanced Cargo Retention and Diversity. Small 2015, 11, 2903-2909. Publisher's VersionAbstract

    Prevention of undesired leakage of encapsulated materials prior to triggered release presents a technological challenge for the practical application of microcapsule technologies in agriculture, drug delivery, and cosmetics. A microfluidic approach is reported to fabricate perfluoropolyether (PFPE)‐based microcapsules with a high core‐shell ratio that show enhanced retention of encapsulated actives. For the PFPE capsules, less than 2% leakage of encapsulated model compounds, including Allura Red and CaCl2, over a four week trial period is observed. In addition, PFPE capsules allow cargo diversity by the fabrication of capsules with either a water‐in‐oil emulsion or an organic solvent as core. Capsules with a toluene‐based core begin a sustained release of hydrophobic model encapsulants immediately upon immersion in an organic continuous phase. The major contribution on the release kinetics stems from the toluene in the core. Furthermore, degradable silica particles are incorporated to confer porosity and functionality to the otherwise chemically inert PFPE‐based polymer shell. These results demonstrate the capability of PFPE capsules with large core–shell ratios to retain diverse sets of cargo for extended periods and make them valuable for controlled release applications that require a low residual footprint of the shell material.

    zieringer2015.pdf
    Polenz, I. ; Weitz, D. A. ; Baret, J. - C. Polyurea Microcapsules in Microfluidics: Surfactant Control of Soft Membranes. Langmuir 2015, 31, 1127–1134. Publisher's VersionAbstract

    Interfacial polymerization techniques offer a versatile route for microcapsule synthesis. We designed a microfluidic process to synthesize monodisperse polyurea microcapsules (PUMCs); the microcapsules are formed by an interfacial polymerization of isocyanate dissolved in the oil and an amine dissolved in water. We measure the mechanical properties of the capsule as well as transport properties through the membrane using two microfluidic methods. We show that the elasticity and the permeability of the shell are controlled by surfactant additives, added during the synthesis. The control of the nanostructure of the shell by surfactants provides new means to design encapsulation systems with tailored mechanical and physicochemical properties.

    polenz2015.pdf
    Akartuna, I. ; Aubrecht, D. M. ; Kodger, T. E. ; Weitz, D. A. Chemically induced coalescence in droplet-based microfluidics. Lab Chip 2015, 15, 1140-1144. Publisher's VersionAbstract

    We present a new microfluidic method to coalesce pairs of surfactant-stabilized water-in-fluorocarbon oil droplets. We achieve this through the local addition of a poor solvent for the surfactant{,} perfluorobutanol{,} which induces cohesion between droplet interfaces causing them to merge. The efficiency of this technique is comparable to existing techniques providing an alternative method to coalesce pairs of droplets.

    akartuna2015.pdf
    Shimanovich, U. ; Efimov, I. ; Mason, T. O. ; Flagmeier, P. ; Buell, A. K. ; Gedanken, A. ; Linse, S. ; Åkerfeldt, K. S. ; Dobson, C. M. ; Weitz, D. A. ; et al. Protein Microgels from Amyloid Fibril Networks. ACS Nano 2015, 9 43–51. Publisher's VersionAbstract

    Nanofibrillar forms of proteins were initially recognized in the context of pathology, but more recently have been discovered in a range of functional roles in nature, including as active catalytic scaffolds and bacterial coatings. Here we show that protein nanofibrils can be used to form the basis of monodisperse microgels and gel shells composed of naturally occurring proteins. We explore the potential of these protein microgels to act as drug carrier agents, and demonstrate the controlled release of four different encapsulated drug-like small molecules, as well as the component proteins themselves. Furthermore, we show that protein nanofibril self-assembly can continue after the initial formation of the microgel particles, and that this process results in active materials with network densities that can be modulated in situ. We demonstrate that these materials are nontoxic to human cells and that they can be used to enhance the efficacy of antibiotics relative to delivery in homogeneous solution. Because of the biocompatibility and biodegradability of natural proteins used in the fabrication of the microgels, as well as their ability to control the release of small molecules and biopolymers, protein nanofibril microgels represent a promising class of functional artificial multiscale materials generated from natural building blocks.

    shimanovich2015.pdf
    2014
    Fan, J. ; Li, Y. ; Bisoyi, H. K. ; Zola, R. S. ; Yang, Deng-ke, B. T. J. W. D. A. L. Q. Light-Directing Omnidirectional Circularly Polarized Reflection from Liquid-Crystal Droplets. Angewandte Chemie International Edition 2014, 54, 2160-2164. Publisher's VersionAbstract

    Constructing and tuning self‐organized three‐dimensional (3D) superstructures with tailored functionality is crucial in the nanofabrication of smart molecular devices. Herein we fabricate a self‐organized, phototunable 3D photonic superstructure from monodisperse droplets of one‐dimensional cholesteric liquid crystal (CLC) containing a photosensitive chiral molecular switch with high helical twisting power. The droplets are obtained by a glass capillary microfluidic technique by dispersing into PVA solution that facilitates planar anchoring of the liquid‐crystal molecules at the droplet surface, as confirmed by the observation of normal incidence selective circular polarized reflection in all directions from the core of individual droplet. Photoirradiation of the droplets furnishes dynamic reflection colors without thermal relaxation, whose wavelength can be tuned reversibly by variation of the irradiation time. The results provided clear evidence on the phototunable reflection in all directions.

    2014_angew_fan.pdf
    Kim, S. - H. ; Park, J. - G. ; Choi, T. M. ; Manoharan, V. N. ; Weitz, D. A. Osmotic-pressure-controlled concentration of colloidal particles in thin-shelled capsules. Nature communications 2014, 5 3068. Publisher's VersionAbstract

    Colloidal crystals are promising structures for photonic applications requiring dynamic control over optical properties. However, for ease of processing and reconfigurability, the crystals should be encapsulated to form ‘ink’ capsules rather than confined in a thin film. Here we demonstrate a class of encapsulated colloidal photonic structures whose optical properties can be controlled through osmotic pressure. The ordering and separation of the particles within the microfluidically created capsules can be tuned by changing the colloidal concentration through osmotic pressure-induced control of the size of the individual capsules, modulating photonic stop band. The rubber capsules exhibit a reversible change in the diffracted colour, depending on osmotic pressure, a property we call osmochromaticity. The high encapsulation efficiency and capsule uniformity of this microfluidic approach, combined with the highly reconfigurable shapes and the broad control over photonic properties, make this class of structures particularly suitable for photonic applications such as electronic inks and reflective displays.

    2014_natcomm_kim.pdf
    Deng, N. - N. ; Wang, W. ; Ju, X. - J. ; Xie, R. ; Weitz, D. A. ; Chu, L. - Y. Reply to the ‘Comment on “Wetting-induced formation of controllable monodisperse multiple emulsions in microfluidics”’by J. Guzowski and P. Garstecki, Lab Chip, 2014, 14, DOI: 10.1039/C3LC51229K. Lab on a Chip 2014, 14, 1479–1480. Publisher's VersionAbstract

    A graphical abstract is available for this content.

    2014_loc_deng.pdf
    Thon, J. N. ; Mazutis, L. ; Wu, S. ; Sylman, J. L. ; Ehrlicher, A. ; Machlus, K. R. ; Feng, Q. ; Lu, S. ; Lanza, R. ; Neeves, K. B. ; et al. Platelet bioreactor-on-a-chip. Blood 2014, 124, 1857–1867. Publisher's VersionAbstract

    Jonathan N. Thon1,2,3, Linas Mazutis3,4,5, Stephen Wu1, Joanna L. Sylman6, Allen Ehrlicher4,7, Kellie R. Machlus1,2, Qiang Feng8, Shijiang Lu8, Robert Lanza8, Keith B. Neeves6,9, David A. Weitz4, and Joseph E. Italiano Jr1,2,3,101Department of Medicine, Brigham and Women’s Hospital, Boston, MA; 2Harvard Medical School, Boston, MA; 3Platelet BioGenesis, Chestnut Hill, MA; 4School of Engineering and Applied Sciences, Harvard University, Cambridge, MA; 5Institute of Biotechnology, Vilnius University, Vilnius, Lithuania; 6Department of Chemical and Biological Engineering, Colorado School of Mines, Golden, CO; 7Department of Bioengineering, McGill University, Montreal, Canada; 8Advanced Cell Technologies, Marlborough, MA; 9Department of Pediatrics, University of Colorado, Denver, Aurora, CO; and 10Department of Surgery, Vascular Biology Program, Boston Children’s Hospital, Boston, MAKey PointsWe have developed a biomimetic microfluidic platelet bioreactor that recapitulates bone marrow and blood vessel microenvironments.Application of shear stress in this bioreactor triggers physiological proplatelet production, and platelet release.AbstractPlatelet transfusions total >2.17 million apheresis-equivalent units per year in the United States and are derived entirely from human donors, despite clinically significant immunogenicity, associated risk of sepsis, and inventory shortages due to high demand and 5-day shelf life. To take advantage of known physiological drivers of thrombopoiesis, we have developed a microfluidic human platelet bioreactor that recapitulates bone marrow stiffness, extracellular matrix composition, micro-channel size, hemodynamic vascular shear stress, and endothelial cell contacts, and it supports high-resolution live-cell microscopy and quantification of platelet production. Physiological shear stresses triggered proplatelet initiation, reproduced ex vivo bone marrow proplatelet production, and generated functional platelets. Modeling human bone marrow composition and hemodynamics in vitro obviates risks associated with platelet procurement and storage to help meet growing transfusion needs.Submitted May 9, 2014.Accepted July 8, 2014.© 2014 by The American Society of Hematology

    thon2014.pdf
    Schmid, L. ; Weitz, D. A. ; Franke, T. Sorting drops and cells with acoustics: acoustic microfluidic fluorescence-activated cell sorter. Lab Chip 2014, 14, 3710-3718. Publisher's VersionAbstract

    We describe a versatile microfluidic fluorescence-activated cell sorter that uses acoustic actuation to sort cells or drops at ultra-high rates. Our acoustic sorter combines the advantages of traditional fluorescence-activated cell (FACS) and droplet sorting (FADS) and is applicable for a multitude of objects. We sort aqueous droplets{,} at rates as high as several kHz{,} into two or even more outlet channels. We can also sort cells directly from the medium without prior encapsulation into drops; we demonstrate this by sorting fluorescently labeled mouse melanoma cells in a single phase fluid. Our acoustic microfluidic FACS is compatible with standard cell sorting cytometers{,} yet{,} at the same time{,} enables a rich variety of more sophisticated applications.

    schmid2014.pdf
    Lin, T. ; Rubinstein, S. M. ; Korchev, A. ; Weitz, D. A. Pattern Formation of Charged Particles in an Electric Field. Langmuir 2014, 30, 12119-12123. Publisher's VersionAbstract

    The application of an electric field to a suspension of charged particles can lead to the formation of patterns due to electrohydrodynamic instabilities which remain poorly understood. We elucidate this behavior by visualizing the dynamics of charged carbon black particles suspended in a nonpolar solvent in response to an electric field. As the particles are transported across a microfluidic channel, an instability occurs in which the initially uniform, rapidly advancing particle front develops fingers. Furthermore, when the direction of the applied field is repeatedly switched, the particles localize into a remarkably well-defined periodic pattern which reflects an interplay between the fingering instability and particle diffusion.

    lin2014.pdf
    Polenz, I. ; Datta, S. S. ; Weitz, D. A. Controlling the Morphology of Polyurea Microcapsules Using Microfluidics. Langmuir 2014, 30, 13405–13410. Publisher's VersionAbstract

    We use microfluidics to continuously produce monodisperse polyurea microcapsules (PUMCs) having either aqueous or nonaqueous cores. The microcapsule shells are formed by the reaction between an isocyanate, dissolved in oil, and an amine, dissolved in water, at the surface of oil-in-water or water-in-oil drops immediately as they are formed. Different microcapsule morphologies can be generated using our approach. The thickness of the microcapsule shell increases with an increase in the amine solubility in the oil; this finding provides a simple mechanism by which the PUMC shell thickness can be controlled.

    polenz2014.pdf
    Rowat, A. C. ; Sinha, N. N. ; Sörensen, P. M. ; Campàs, O. ; Castells, P. ; Rosenberg, D. ; Brenner, M. P. ; Weitz, D. A. The kitchen as a physics classroom. Physics Education 2014, 49, 512. Publisher's VersionAbstract

    Cooking is a tangible, familiar, and delicious tool for teaching physics, which is easy to implement in a university setting. Through our courses at Harvard and UCLA, each year we are engaging hundreds of undergraduate students, primarily non-science majors, in science concepts and the scientific research process. We find that weekly lectures by chefs and professors, paired with edible lab experiments, generate enthusiasm and provide strong motivation for students to learn physics. By the end of the course, students are able to conduct independent scientific research and present their results in a final science fair. Given the considerable broad appeal of food and cooking, the topic could be adapted to other post-secondary as well as secondary-level courses.

    rowat2014.pdf
    Duncanson, W. J. ; Arriaga, L. R. ; Ung, W. L. ; Kopechek, J. ; Porter, T. ; Weitz, D. A. Microfluidic Fabrication of Perfluorohexane-Shelled Double Emulsions for Controlled Loading and Acoustic-Triggered Release of Hydrophilic Agents. Langmuir 2014, 30, 13765–13770. Publisher's VersionAbstract

    The ability of low boiling point liquid perfluorocarbons (PFCs) to undergo a phase change from a liquid to a gas upon ultrasound irradiation makes PFC-based emulsions promising vehicles for triggered delivery of payloads. However, loading hydrophilic agents into PFC-based emulsions is difficult due to their insolubility in PFC. Here, we address this challenge by taking advantage of microfluidic technologies to fabricate double emulsions consisting of large aqueous cores and a perfluorohexane (PFH) shell, thus yielding high loading capacities for hydrophilic agents. Using this technology, we efficiently encapsulate a model hydrophilic agent within the emulsions and study its response to ultrasound irradiation. Using a combination of optical and acoustic imaging methods, we observe payload release upon acoustic vaporization of PFH. Our work demonstrates the utility of microfluidic techniques for controllably loading hydrophilic agents into PFH-based emulsions, which have great potential for acoustically triggered release.

    duncanson2014.pdf
    Jensen, K. E. ; Weitz, D. A. ; Spaepen, F. Local shear transformations in deformed and quiescent hard-sphere colloidal glasses. Physical Review E 2014, 90, 042305. Publisher's VersionAbstract
    We perform a series of deformation experiments on a monodisperse, hard-sphere colloidal glass while simultaneously following the three-dimensional trajectories of roughly 50000 individual particles with a confocal microscope. In each experiment, we deform the glass in pure shear at a constant strain rate [(1–5)×10−5 s−1] to maximum macroscopic strains (5%–10%) and then reverse the deformation at the same rate to return to zero macroscopic strain. We also measure three-dimensional particle trajectories in an identically prepared quiescent glass in which the macroscopic strain is always zero. We find that shear transformation zones exist and are active in both sheared and quiescent colloidal glasses, revealed by a distinctive fourfold signature in spatial autocorrelations of the local shear strain. With increasing shear, the population of local shear transformations develops more quickly than in a quiescent glass and many of these transformations are irreversible. When the macroscopic strain is reversed, we observe partial elastic recovery, followed by plastic deformation of the opposite sign, required to compensate for the irreversibly transformed regions. The average diameter of the shear transformation zones in both strained and quiescent glasses is slightly more than two particle diameters.
    jensen2014.pdf

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