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.

Abbaspourrad, A. ; Duncanson, W. J. ; Lebedeva, N. ; Kim, S. - H. ; Zhushma, A. P. ; Datta, S. S. ; Dayton, P. A. ; Sheiko, S. S. ; Rubinstein, M. ; Weitz, D. A. Microfluidic fabrication of stable gas-filled microcapsules for acoustic contrast enhancement. Langmuir 2013, 29, 12352-12357.Abstract

We introduce a facile approach for the production of gas-filled microcapsules designed to withstand high pressures. We exploit microfluidics to fabricate water-filled microcapsules that are then externally triggered to become gas-filled, thus making them more echogenic. In addition, the gas-filled microcapsules have a solid polymer shell making them resistant to pressure-induced buckling, which makes them more mechanically robust than traditional prestabilized microbubbles; this should increase the potential of their utility for acoustic imaging of porous media with high hydrostatic pressures such as oil reservoirs.

Liu, D. ; Herranz-Blanco, B. ; Makila, E. ; Arriaga, L. R. ; Mirza, S. ; Weitz, D. A. ; Sandler, N. ; Salonen, J. ; Hirvonen, J. ; Santos, H. A. Microfluidic templated mesoporous silicon-solid lipid microcomposites for sustained drug delivery. ACS Applied Materials & Interfaces 2013, 5 12127-12134.Abstract

A major challenge for a drug-delivery system is to engineer stable drug carriers with excellent biocompatibility, monodisperse size, and controllable release profiles. In this study, we used a microfluidic technique to encapsulate thermally hydrocarbonized porous silicon (THCPSi) microparticles within solid lipid microparticles (SLMs) to overcome the drawbacks accompanied by THCPSi microparticles. Formulation and process factors, such as lipid matrixes, organic solvents, emulsifiers, and methods to evaporate the organic solvents, were all evaluated and optimized to prepare monodisperse stable SLMs. FTIR analysis together with confocal images showed the clear deposition of THCPSi microparticles inside the monodisperse SLM matrix. The formation of monodisperse THCPSi solid lipid microcomposites (THCPSi SLMCs) not only altered the surface hydrophobicity and morphology of THCPSi microparticles but also remarkably enhanced their cytocompatibility with intestinal (Caco-2 and HT-29) cancer cells. Regardless of the solubility of the loaded therapeutics (aqueous insoluble, fenofibrate and furosemide; aqueous soluble, methotrexate and ranitidine) and the pH values of the release media (1.2, 5.0, and 7.4), the time for the release of 50% of the payloads from THCPSi SLMC was at least 1.3 times longer than that from the THCPSi microparticles. The sustained release of both water-soluble and -insoluble drugs together with a reduced burst-release effect from monodisperse THCPSi SLMC was achieved, indicating the successful encapsulation of THCPSi microparticles into the SLM matrix. The fabricated THCPSi SLMCs exhibited monodisperse spherical morphology, enhanced cytocompatibility, and prolonged both water-soluble and -insoluble drug release, which makes it an attractive controllable drug-delivery platform.

Koziej, D. ; Floryan, C. ; Sperling, R. A. ; Ehrlicher, A. J. ; Issadore, D. ; Westervelt, R. ; Weitz, D. A. Microwave dielectric heating of non-aqueous droplets in a microfluidic device for nanoparticle synthesis. Nanoscale 2013, 5 5468-5475.Abstract

We describe a microfluidic device with an integrated microwave heater specifically designed to dielectrically heat non-aqueous droplets using time-varying electrical fields with the frequency range between 700 and 900 MHz. The precise control of frequency, power, temperature and duration of the applied field opens up new vistas for experiments not attainable by conventional microwave heating. We use a non-contact temperature measurement system based on fluorescence to directly determine the temperature inside a single droplet. The maximum temperature achieved of the droplets is 50 degrees C in 15 ms which represents an increase of about 25 degrees C above the base temperature of the continuous phase. In addition we use an infrared camera to monitor the thermal characteristics of the device allowing us to ensure that heating is exclusively due to the dielectric heating and not due to other effects like non-dielectric losses due to electrode or contact imperfection. This is crucial for illustrating the potential of dielectric heating of benzyl alcohol droplets for the synthesis of metal oxides. We demonstrate the utility of this technology for metal oxide nanoparticle synthesis, achieving crystallization of tungsten oxide nanoparticles and remarkable microstructure, with a reaction time of 64 ms, a substantial improvement over conventional heating methods.

Rowat, A. C. ; Jaalouk, D. E. ; Zwerger, M. ; Ung, L. W. ; Eydelnant, I. A. ; Olins, D. E. ; Olins, A. L. ; Herrmann, H. ; Weitz, D. A. ; Lammerding, J. Nuclear envelope composition determines the ability of neutrophil-type cells to passage through micron-scale constrictions. Journal of Biological Chemistry 2013, 288, 8610-8618.Abstract

Neutrophils are characterized by their distinct nuclear shape, which is thought to facilitate the transit of these cells through pore spaces less than one-fifth of their diameter. We used human promyelocytic leukemia (HL-60) cells as a model system to investigate the effect of nuclear shape in whole cell deformability. We probed neutrophil-differentiated HL-60 cells lacking expression of lamin B receptor, which fail to develop lobulated nuclei during granulopoiesis and present an in vitro model for Pelger-Huet anomaly; despite the circular morphology of their nuclei, the cells passed through micron-scale constrictions on similar timescales as scrambled controls. We then investigated the unique nuclear envelope composition of neutrophil-differentiated HL-60 cells, which may also impact their deformability; although lamin A is typically down-regulated during granulopoiesis, we genetically modified HL-60 cells to generate a subpopulation of cells with well defined levels of ectopic lamin A. The lamin A-overexpressing neutrophil-type cells showed similar functional characteristics as the mock controls, but they had an impaired ability to pass through micron-scale constrictions. Our results suggest that levels of lamin A have a marked effect on the ability of neutrophils to passage through micron-scale constrictions, whereas the unusual multilobed shape of the neutrophil nucleus is less essential.

Choi, C. - H. ; Weitz, D. A. ; Lee, C. - S. One step formation of controllable complex emulsions: From functional particles to simultaneous encapsulation of hydrophilic and hydrophobic agents into desired position. Advanced Materials 2013, 25, 2536-2541. [PDF]
Kim, S. - H. ; Kim, J. W. ; Kim, D. - H. ; Han, S. - H. ; Weitz, D. A. Polymersomes containing a hydrogel network for high stability and controlled release. Small 2013, 9 124-131.Abstract

Capillary microfluidic devices are used to prepare monodisperse polymersomes consisting of a hydrogel core and a bilayer membrane of amphiphilic diblock-copolymers. To make polymersomes, water-in-oil-in-water double-emulsion drops are prepared as templates through single-step emulsification in a capillary microfluidic device. The amphiphile-laden middle oil phase of the double-emulsion drop dewets from the surface of the innermost water drop, which contains hydrogel prepolymers; this dewetting leads to the formation of a bilayer membrane. Subsequently, the oil phase completely separates from the innermost water drop, leaving a polymersome. Upon UV illumination of the polymersome, the prepolymers encapsulated within the interior are crosslinked, forming a hydrogel core. The hydrogel network within the polymersomes facilitates sustained release of the encapsulated materials and increases the stability of the polymersomes through the formation of a scaffold to support the bilayer. In addition, this approach provides a facile method to make monodisperse hydrogel particles directly dispersed in water.

Di Benedetto, F. ; Fasano, V. ; Persano, L. ; Maruccio, C. ; Mele, E. ; Potente, G. ; Weitz, D. A. ; De Lorenzis, L. ; Pisignano, D. Rolling particle lithography by soft polymer microparticles. Soft Matter 2013, 9 2206-2211.Abstract

Elastomeric polymeric microspheres are employed as a direct-writing tool for the continuous delivery of molecular materials. The mechanical properties enabling patterning are investigated and modelled. The proposed approach provides a low cost and versatile lithographic method for transferring features with real-time dynamic control.

Mazutis, L. ; Gilbert, J. ; Ung, L. W. ; Weitz, D. A. ; Griffiths, A. D. ; Heyman, J. A. Single-cell analysis and sorting using droplet-based microfluidics. Nature Protocols 2013, 8 870-891.Abstract

We present a droplet-based microfluidics protocol for high-throughput analysis and sorting of single cells. Compartmentalization of single cells in droplets enables the analysis of proteins released from or secreted by cells, thereby overcoming one of the major limitations of traditional flow cytometry and fluorescence-activated cell sorting. As an example of this approach, we detail a binding assay for detecting antibodies secreted from single mouse hybridoma cells. Secreted antibodies are detected after only 15 min by co-compartmentalizing single mouse hybridoma cells, a fluorescent probe and single beads coated with anti-mouse IgG antibodies in 50-pl droplets. The beads capture the secreted antibodies and, when the captured antibodies bind to the probe, the fluorescence becomes localized on the beads, generating a clearly distinguishable fluorescence signal that enables droplet sorting at similar to 200 Hz as well as cell enrichment. The microfluidic system described is easily adapted for screening other intracellular, cell-surface or secreted proteins and for quantifying catalytic or regulatory activities. In order to screen similar to 1 million cells, the microfluidic operations require 2-6 h; the entire process, including preparation of microfluidic devices and mammalian cells, requires 5-7 d.

Datta, S. S. ; Chiang, H. ; Ramakrishnan, T. S. ; Weitz, D. A. Spatial fluctuations of fluid velocities in flow through a three-dimensional porous medium. Physical Review Letters 2013, 111.Abstract

We use confocal microscopy to directly visualize the spatial fluctuations in fluid flow through a three-dimensional porous medium. We find that the velocity magnitudes and the velocity components both along and transverse to the imposed flow direction are exponentially distributed, even with residual trapping of a second immiscible fluid. Moreover, we find pore-scale correlations in the flow that are determined by the geometry of the medium. Our results suggest that despite the considerable complexity of the pore space, fluid flow through it is not completely random.

DiLauro, A. M. ; Abbaspourrad, A. ; Weitz, D. A. ; Phillips, S. T. Stimuli-responsive core-shell microcapsules with tunable rates of release by using a depolymerizable poly(phthalaldehyde) membrane. Macromolecules 2013, 46, 3309-3313.Abstract

Flow-focusing microfluidic techniques were used to provide access to core shell microcapsules in which the shell is composed of end tapped poly(phthalaldehydes) that depolymerize completely from head-to-tail in response to fluoride. Microcapsules made from these depolymerizable polymers provide an amplified response to the applied chemical signal, where the rate of the response can be tuned both by varying the length of the polymer and the thickness of the shell wall.

Munster, S. ; Jawerth, L. M. ; Leslie, B. A. ; Weitz, J. I. ; Fabry, B. ; Weitz, D. A. Strain history dependence of the nonlinear stress response of fibrin and collagen networks. Proceedings of the National Academy of Sciences of the United States of America 2013, 110, 12197-12202.Abstract

We show that the nonlinear mechanical response of networks formed from un-cross-linked fibrin or collagen type I continually changes in response to repeated large-strain loading. We demonstrate that this dynamic evolution of the mechanical response arises from a shift of a characteristic nonlinear stress-strain relationship to higher strains. Therefore, the imposed loading does not weaken the underlying matrices but instead delays the occurrence of the strain stiffening. Using confocal microscopy, we present direct evidence that this behavior results from persistent lengthening of individual fibers caused by an interplay between fiber stretching and fiber buckling when the networks are repeatedly strained. Moreover, we show that covalent cross-linking of fibrin or collagen inhibits the shift of the nonlinear material response, suggesting that the molecular origin of individual fiber lengthening may be slip of monomers within the fibers. Thus, a fibrous architecture in combination with constituents that exhibit internal plasticity creates a material whose mechanical response adapts to external loading conditions. This design principle may be useful to engineer novel materials with this capability.



Abbaspourrad, A. ; Carroll, N. J. ; Kim, S. - H. ; Weitz, D. A. Surface functionalized hydrophobic porous particles toward water treatment application. Advanced Materials 2013, 25, 3215-3221.Abstract

A microfluidic-based approach for the fabrication of organic contaminants absorbing core-shell particles is demonstrated. The hydrophobic porous core absorbs oil while the hydrophilic surface enables the particles to be well-dispersed in aqueous solutions. These particles can uptake oil from aqueous solution saturated with oil or via direct contact with oil blobs as depicted in the figure.

Guo, M. ; Ehrlicher, A. J. ; Mahammad, S. ; Fabich, H. ; Jensen, M. H. ; Moore, J. R. ; Fredberg, J. J. ; Goldman, R. D. ; Weitz, D. A. The role of vimentin intermediate filaments in cortical and cytoplasmic mechanics. Biophysical Journal 2013, 105, 1562-1568.Abstract

The mechanical properties of a cell determine many aspects of its behavior, and these mechanics are largely determined by the cytoskeleton. Although the contribution of actin filaments and microtubules to the mechanics of cells has been investigated in great detail, relatively little is known about the contribution of the third major cytoskeletal component, intermediate filaments (IFs). To determine the role of vimentin IF (VIF) in modulating intracellular and cortical mechanics, we carried out studies using mouse embryonic fibroblasts (mEFs) derived from wild-type or vimentin(-/-) mice. The VIFs contribute little to cortical stiffness but are critical for regulating intracellular mechanics. Active microrheology measurements using optical tweezers in living cells reveal that the presence of VIFs doubles the value of the cytoplasmic shear modulus to similar to 10 Pa. The higher levels of cytoplasmic stiffness appear to stabilize organelles in the cell, as measured by tracking endogenous vesicle movement. These studies show that VIFs both increase the mechanical integrity of cells and localize intracellular components.

Krummel, A. T. ; Datta, S. S. ; Muenster, S. ; Weitz, D. A. Visualizing multiphase flow and trapped fluid configurations in a model three-dimensional porous medium. Aiche Journal 2013, 59, 1022-1029.Abstract

We report an approach to fully visualize the flow of two immiscible fluids through a model three-dimensional (3-D) porous medium at pore-scale resolution. Using confocal microscopy, we directly image the drainage of the medium by the nonwetting oil and subsequent imbibition by the wetting fluid. During imbibition, the wetting fluid pinches off threads of oil in the narrow crevices of the medium, forming disconnected oil ganglia. Some of these ganglia remain trapped within the medium. By resolving the full 3-D structure of the trapped ganglia, we show that the typical ganglion size, as well as the total amount of residual oil, decreases as the capillary number Ca increases; this behavior reflects the competition between the viscous pressure in the wetting fluid and the capillary pressure required to force oil through the pores of the medium. This work thus shows how pore-scale fluid dynamics influence the trapped fluid configurations in multiphase flow through 3-D porous media. (C) 2013 American Institute of Chemical Engineers AIChE J, 59: 1022-1029, 2013