Experimental Soft Condensed Matter Group

Experimental Soft Condensed
Matter Group
Prof. David A. Weitz
School of Engineering and Applied Sciences / Department of Physics
Harvard University, Cambridge, MA 02138

RESEARCH AREAS

COLLOID PHYSICS
FLOW IN MICROCHANNELS

PARTICLE SYNTHESIS ENCAPSULATION

MECHANICS OF BIOLOGICAL NETWORKS BIOPHYSICS OF CELLS

RHEOLOGY AND MICRORHEOLOGY BIOLOGY IN MICROFLUIDIC DEVICES

SPLASHING, MOLECULAR AGGREGATION, AND EMULSION GELS OLDER RESEARCH

COLLOID PHYSICS
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Colloidal Crystals as Model Systems to Study Solid State Phenomena: At high volume fractions, hard sphere colloids form close packed crystals that behave remarkably similar to simple metals on the atomic scale. Using confocal microscopy these crystals can be imaged in three dimensions with atomic resolution. This allows the in situ observation of solid state dynamics (for example dislocation, grain boundary or vacancy movement) that are not accessible experimentally in atomic crystals.

PLuTARC: Target-Locking Microscopy: In any typical data gathering process, objects are observed from a fixed viewpoint (think of a camera on a tripod). If the objects are moving, this limits the observation time, as the objects move out of the field of view. In a microscope, this is a particularly severe problem when studying moving objects like swimming cells, or freely-diffusing cluster of colloidal beads. What we've done with the PLuTARC (Peter Lu Target-Locking Acquisition in Real-time Confocal) system is to implement target-locking. Images from the microscope are analyzed in real-time, allowing determination of the largest object's center.

Drying of a colloidal suspension: How does a colloidal suspension dry? Is evaporation the only factor we need to consider in this process? By watching the drying of an index matched colloidal suspension with a confocal microscope, we found that drying is a two-stage process: in the first stage, due to faster evaporation rate at edge, colloidal particles accumulate and compact at the edge, forming a porous medium filled by solvent; after all the particles are packed, the second stage starts: air invades this porous medium and solvent retreats, eventually all liquid is replaced by air.

Mechanical Properties of a Colloidal Gel by Depletion Interaction: We disperse bigger colloidal particles in the sea of small particles that are usually micelles or polymers. When big particles get close, a depletion volume where the smaller particles cannot access is formed between two bigger particles. Due to osmotic pressure, the bigger particles are pushed together by smaller particles. The potential depth is proportional to the depletion volume and the number concentration of the small particles. The potential width is the same as the diameter of the small particle. Other semidilute colloidal systems also form networks with depletion interaction.

The Physics of Attractive Colloids: We use confocal microscopy to determine the three-dimensional positions of thousands of particles as a function of time. We control the interactions between the particles to make them attractive, and can control the range and strength of this attraction potential. We are able to create and observe a number of phases, including equilibrium fluids, a kinetically-arrested gels, and large clusters that persist. Our ultimate aim is to establish a general framework for understanding the behavior of attractive colloid systems, and which physics drives their formation and properties. One particular limit, equilibrium phase separation near the critical, takes a very long time to observe, and we therefore conduct experiments in space, where we don't have to worry about long-time issues of sedimentation.

Transport and Jamming of Colloids in Porous Materials: We study the flow and clogging of colloidal particles in porous materials. Our experiments aim at getting a better understanding of the mechanisms that lead to flow-driven jamming of colloids in porous materials. We also study the influence of particle infiltration upon the macroscopic mechanical behavior of a porous material.

Shear-melting colloidal glasses: We investigate the structure and dynamics of attractive and repulsive colloidal glasses using a confocal microscope. We want to understand in what way both types of glasses differ on the single particle level and study how shear strain influences dynamics of these systems.

Strain-Rate Frequency Superposition: A new approach to oscillatory rheology for soft materials.

Investigation of Grain Boundaries in Colloidal Crystals: Almost all engineering applications of metals involve their use in polycrystalline form. Recently the emphasis in the study of mechanical properties has moved away from the processes which occur inside the individual grains to those which are governed by the boundaries between the grains. Diverse phenomena such as high temperature creep, superplasticity, recrystallization, yielding and embrittlement all depend strongly on effects at grain boundaries. Grain boundaries are also important for diffusion phenomena as they provide pathways for diffusions into or within a material that are orders of magnitude faster than through crystalline regions. Interactions of grain boundaries and defects are also a topic of current research. Recent studies emphasize the role of grain boundaries for premelting of a crystal. Despite the important role of grain boundaries in material properties our knowledge at the microscopic level is limited. The direct observation of grain boundary structure is limited by the lack of resolution of experimental techniques such as high resolution transmission electron microscopy. Thus colloidal crystals can serve as a model system to study grain boundary characteristics as they are much larger and show a much slower dynamics which makes them accesible to experimental techniques like confocal microscopy.

FLOW IN MICROCHANNELS
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Glass coating for PDMS channels by sol-gel methods: Polydimethylsiloxane (PDMS) is widely used for fabrication of microfluidic devices: it is inexpensive and it can be fashioned to have complex channel structures. However, PDMS channels have several drawbacks. Even when cured, PDMS remains permeable to liquids and gases, which can affect reactions that occur in the channels. Organic solvents can swell PDMS significantly, seriously degrading device performance. The limited chemical compatibility of PDMS is, therefore, a major problem that can limit the wider application of PDMS to microfluidic technology. We coat PDMS microfluidic devices with a glass-like layer using sol-gel chemistry. The coating greatly increases the chemical resistance of the channels, enabling the use of organic solvents. In addition, the coating can be functionalized with a wide range of silanes, for example, to make the channels either hydrophilic or hydrophobic.

Fabrication of micron-scaled monodisperse oil-in-water emulsions in glass microcapillaries: We work on generating monodisperse oil-in-water emulsions below conventional droplet sizes using droplet breakup in glass microcapillaries. Smaller droplets necessitates narrower channels. In the micron range, typical pressure required is too high for conventional microfluidic devices. In this work, we show that micron-sized monodisperse emulsions can be prepared in a modified microcapillary device. Moreover, we present potential applications for these emulsion droplets in both materials engineering and fundamental research.

Geometrically Controlled Jet-Like Instabilities in Microfluidic Two-Phase Flows: We are interested in the effects of confinement in two phase co-flows in microfluidic devices. When the flow rate of the inner fluid is small compared to the flow rate of the outer fluid, and the resulting width of the inner fluid is smaller than the height of the channel, the inner fluid breaks into droplets, as expected for a three-dimensional system. On the other hand, when the width of the second phase becomes comparable to the height of the microfluidic device, Rayleigh capillary instabilities are suppressed, and the inner fluid forms a jet that does not break, as might be expected for a purely two-dimensional system. We show that by changing the dimensions of the microfluidic channel we can transition from a stable co-flow to drop break-up. These results can be explained with a model of this two phase flow.

Giant Phospholipid Vesicles from Double Emulsions: Vesicles made from phospholipids (also known as liposomes) provide excellent model systems for studying the biophysics of plasma membranes. Also these liposomes hold much promise in the areas of encapsulation and delivery of active ingredients. In this project, we aim to fabricate phospholipid vesicles from double emulsions (water-in-oil-in-water droplets) which are prepared by using a glass microcapillary device. Using our technique, it is possible to continuously generate monodisperse liposomes and at the same time achieve high encapsulation efficiency.

Transport and Jamming of Colloids in Porous Materials: We study the flow and clogging of colloidal particles in porous materials. Our experiments aim at getting a better understanding of the mechanisms that lead to flow-driven jamming of colloids in porous materials. We also study the influence of particle infiltration upon the macroscopic mechanical behavior of a porous material.

Microfluidics as a Formulation Tool: We investigate the usefulness of microfluidic devices as a low energy-input formulation tool for producing emulsions in a controlled fashion.

PARTICLE SYNTHESIS
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Self-assembled structures from microgel particles using microfluidics:Microgel particles are cross-linked latex particles that swell in appropriate solvents. They are extensively used in the surface coating industry and are being researched for applications in the printing, pharmaceutical and cosmetics industries. Their ability to swell/ de-swell in response to changes in pH, temperature, or other stimuli makes them interesting candidates for targeted release applications. This study is geared towards the fabrication of novel self-assembled structures from microgel particles using microfluidic devices. The use of capillary based microfluidic devices allows us to create monodisperse droplets which should help us gain precise control over the release kinetics. We intend to develop a better understanding of the physics behind the self-organization of such structures and their properties.

ENCAPSULATION
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Giant Phospholipid Vesicles from Double Emulsions: Vesicles made from phospholipids (also known as liposomes) provide excellent model systems for studying the biophysics of plasma membranes. Also these liposomes hold much promise in the areas of encapsulation and delivery of active ingredients. In this project, we aim to fabricate phospholipid vesicles from double emulsions (water-in-oil-in-water droplets) which are prepared by using a glass microcapillary device. Using our technique, it is possible to continuously generate monodisperse liposomes and at the same time achieve high encapsulation efficiency.

Droplet Based Microfluidics for High-Throughput Monoclonal Antibody Screening: We exploit droplet based microfluidics in order to develop a high-throughput assay for monoclonal antibody screening. We use monodisperse aqueous emulsion droplets in a continuous oil phase as picoliter-sized reaction volumes. Single antibody producing hybridoma cells are encapsulated in these drops, which serve as individual compartments. Upon incubation for several hours the cells produce monoclonal antibodies. Co-encaplsulation with beads, which are coated with a particular target antigen, leads to attachment of the primary antibodies to the surface of the beads. Successive fusion of the drops containing the cells and beads with drops containing a fluorescent secondary anti-mouse antibody leads to a concentration of fluorescence around the beads. We are able to detect this fluorescent signal and sort the drops containing cells that produce the desired antibody. Live cells can be recovered and used for monoclonal antibody production against the specified antigen.

Directed evolution of enzymes in microfluidic devices: We are recreating the mechanisms of natural selection in the laboratory at the single enzyme level.One goal is to engineer new enzyme functions using this method. These may have interesting industrial, synthetic, or therapeutic uses. In addition, In vitro evolution also gives us the ability to observe evolutionary intermediates, control selective pressure, mutation rate, and population sizes in ways that aren't possible using other methods, and this allows us to ask new questions about the evolutionary process itself.

MECHANICS OF BIOLOGICAL NETWORKS
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Visualization and Analysis of Biopolymer Networks under Shear: When you impose a small strain on a sample its response will be roughly linear. In other words, the amount of force necessary to deform the sample a given amount is roughly constant. As you increase the strain most materials will start to weaken and eventually break (strain weaken). Interestingly, many biopolymer networks exhibit the opposite behavior. Namely, as you increasingly strain them, they stiffen before they break. (strain stiffening).

There has been a lot of theoretical work trying to predict and model how individual filament dynamics give rise to strain stiffening. We are taking an experimental approach and directly visualize the individual filaments using confocal microscopy as the networks undergo shear.

Rheology of Intermediate Filament Solutions: Cells interact mechanically with their environment through their cytoskeleton, a network consisting largely of filamentous protein polymers. Reconstituted solutions and networks of these biopolymers have rich rheological and elastic properties that arise from their semi-flexibility, with thermal persistence lengths comparable to their contour length. While the viscoelastic properties of reconstituted models of other cytoskeletal filaments, most notably F-actin, have been widely studied in vitro, relatively little is known about the network properties of intermediate filaments (IF). Such knowledge is urgently needed for understanding how disease-causing inherited mutations in human IF proteins yield an increase in cell fragility in response to mechanical stresses. We study both the vimentin and neurofilament networks in vitro by using the multiple particle tracking technique and the conventional rheometry.

Rheology of Microtubule Solutions: In eukaryotic cells, microtubules form a network that guides active intracellular transport and supports the overall cell structure. Microtubules also play an important role in the organization of cell locomotion, morphogenesis, and reproduction. By studying the mechanical properties of microtubules we hope to understand more about the mechanism of these fundamental cellular processes. We study the microtubule networks in vitro by using the multiple particle tracking technique that has previously been successfully utilized with F-actin networks in our lab.

Cell Mechanics and Cross-linked Actin Networks: We would like to understand how mechanical stimuli are sensed by the cell, transmitted via signaling pathways, and ultimately result in complex mechanical responses. Toward this goal, we investigate the mechanics of actin filament networks and how the properties of these networks can be modulated and regulated by cross-linking proteins such as filamin.

BIOPHYSICS OF CELLS
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Quantifying forces generated by cells in three dimensions: Two-dimensional cell traction forces can be typically obtained by tracking substrate patterns and their deformation as the cell is actively exerting forces. From a measured displacement field, one can obtain quantitative information on the stresses exerted by the cell; however, this is only possible if several assumptions hold regarding the substrate:
the material is isotropic;
the material is elastic;
the material is homogeneous;
the material is linear (not necessary, though it greatly simplifies calculations)
the material deforms in an affine way;
In three-dimensional tissue equivalents (cells embedded in 3D collagen matrix), support is provided by a collagen matrix, with typical concentrations of the order of 1mg/mL, mesh sizes in the micron range and fiber diameters of hundreds of nanometers. Several assumptions above do not hold in this case, at least not at the length-scale of a cell, which can be presumed to be the relevant one. It is unclear, though, how important each of these assumptions is. Therefore, we wish to compare quantitative stress/force measurements obtained through different models:
homogeneous, continous, isotropic, matrix
discrete fiber architecture

Curvature-modulated Compositional and Dynamic Heterogeneity of Skin Lipid Structures: Stratum corneum (SC) is the outermost layer of the epidermis (the outermost layer of the skin) and serves an important barrier function by keeping molecules from passing into and out of the skin, thus protecting the lower layers of skin. The organization of lipids in the intercellular regions of the SC is known to play a crucial role in determining the permeation properties of SC. The goal of this research project is to elucidate the effect of high curvature on the structure and properties of SC lipids.

Brain Tumor Growth Model: For several years, members of the Weitz lab have been working in collaboration with several other groups (Tom Deisboeck at Massachusetts General Hospital, Mike Berens at Tgen, Len Sander at the University of Michigan, and Antonio Chiocca at Ohio State University) to understand details about the motion of a particular type of brain tumor cell, Glioblastoma Multiforme (GBM). GBM is a brain cancer that kills its victims quickly because it is highly invasive and because surgery to remove such tumors inevitably leaves much of the tenuous network of invasive cancer cells behind.

Rheology of Microtubule Solutions: In eukaryotic cells, microtubules form a network that guides active intracellular transport and supports the overall cell structure. Microtubules also play an important role in the organization of cell locomotion, morphogenesis, and reproduction. By studying the mechanical properties of microtubules we hope to understand more about the mechanism of these fundamental cellular processes. We study the microtubule networks in vitro by using the multiple particle tracking technique that has previously been successfully utilized with F-actin networks in our lab.

Cell Mechanics and Cross-linked Actin Networks: We would like to understand how mechanical stimuli are sensed by the cell, transmitted via signaling pathways, and ultimately result in complex mechanical responses. Toward this goal, we investigate the mechanics of actin filament networks and how the properties of these networks can be modulated and regulated by cross-linking proteins such as filamin.

Cell Prestress, Stiffness, and Density: To explore the prestress mechanism of cell elasticity we have cultured adherent cos-7 cells on PDMS substrates with periodic patterns of varying stiffness and constant chemical environment. We have varied the moduli and the wavelengths of the patterned regions, and have observed preferred growth of cells on stiffer regions.

Collective Contractile Dynamics in Confluent Cell Layers: Many types of cells are sensitive to the mechanical properties of their environment. In cultures of fibroblasts and endothelial cells, for example, it has been shown that cell morphology and motility are sensitive to substrate elasticity and are related to the traction forces exerted by cells. It was shown that in human airway soft muscle cells, the stiffness of the cell itself increases in proportion to the traction forces the cell exerts on the substrate. Taken together, these results suggest that, at confluence, cells will exhibit different mechanical behavior than at sparse densities because in a confluent layer the ?mechanical environment? is active; it is composed of a substrate and neighboring cells. To explore collective mechanical behavior of cells at confluent densities, we cultured cos-7 epithelial cells on PDMS (Young?s modulus ~10 kPa), and monitored the motion of beads embedded below the elastomer surface.

RHEOLOGY AND MICRORHEOLOGY
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Rheology of solid-stabilized emulsions: Emulsions are mixtures of two immiscible fluids, as droplets of one dispersed in the other fluid. They are used in cosmetics, food industry, pharmaceuticals, petroleum industry… In the oilfield they are also present when unwanted, as formation water and oil mix easy due to their different viscosities. Emulsions are important especially because of their rheological properties. Dilute emulsions are liquid-like and their viscosity can be adjusted by changing the concentration of the dispersed phase. Highly concentrated emulsions, on the other hand, can be solid-like with a high elastic modulus. This is due to droplets, packed together, further deforming upon shear. Additional surface area requires energy, hence the material is elastic. The nature of this elasticity is well understood for the case of surfactant-stabilized emulsions. But what if surfactants were solid particles? How would that affect the rheology?

Mechanical Properties of a Colloidal Gel by Depletion Interaction: We disperse bigger colloidal particles in the sea of small particles that are usually micelles or polymers. When big particles get close, a depletion volume where the smaller particles cannot access is formed between two bigger particles. Due to osmotic pressure, the bigger particles are pushed together by smaller particles. The potential depth is proportional to the depletion volume and the number concentration of the small particles. The potential width is the same as the diameter of the small particle. Other semidilute colloidal systems also form networks with depletion interaction.

Rheology of Intermediate Filament Solutions: Cells interact mechanically with their environment through their cytoskeleton, a network consisting largely of filamentous protein polymers. Reconstituted solutions and networks of these biopolymers have rich rheological and elastic properties that arise from their semi-flexibility, with thermal persistence lengths comparable to their contour length. While the viscoelastic properties of reconstituted models of other cytoskeletal filaments, most notably F-actin, have been widely studied in vitro, relatively little is known about the network properties of intermediate filaments (IF). Such knowledge is urgently needed for understanding how disease-causing inherited mutations in human IF proteins yield an increase in cell fragility in response to mechanical stresses. We study both the vimentin and neurofilament networks in vitro by using the multiple particle tracking technique and the conventional rheometry.

Rheology of Microtubule Solutions: In eukaryotic cells, microtubules form a network that guides active intracellular transport and supports the overall cell structure. Microtubules also play an important role in the organization of cell locomotion, morphogenesis, and reproduction. By studying the mechanical properties of microtubules we hope to understand more about the mechanism of these fundamental cellular processes. We study the microtubule networks in vitro by using the multiple particle tracking technique that has previously been successfully utilized with F-actin networks in our lab.

Cell Mechanics and Cross-linked Actin Networks: We would like to understand how mechanical stimuli are sensed by the cell, transmitted via signaling pathways, and ultimately result in complex mechanical responses. Toward this goal, we investigate the mechanics of actin filament networks and how the properties of these networks can be modulated and regulated by cross-linking proteins such as filamin.

Strain-Rate Frequency Superposition: A new approach to oscillatory rheology for soft materials.

Rheology of solid-stabilized emulsions: It has been studied for the case of surfactants -- but how does the presence of solid particles affect rheology?
We believe the rigidity of particles, and more so their organization, leads to different response to deformation. Particles interact through balance of electrostatic and capillary forces, that tends to organize them at the interface. So does their concentration, the necessity to cover drops and protect from coalescing. The interfaces are structured, able to store energy upon deformation. We study the rheology of this packing of a packing -- the interplay between 3D structure of emulsion droplets and 2D structure of colloidal particles at their interfaces.

BIOLOGY IN MICROFLUIDIC DEVICES
(back to top) or (front)

Glass coating for PDMS channels by sol-gel methods: Polydimethylsiloxane (PDMS) is widely used for fabrication of microfluidic devices: it is inexpensive and it can be fashioned to have complex channel structures. However, PDMS channels have several drawbacks. Even when cured, PDMS remains permeable to liquids and gases, which can affect reactions that occur in the channels. Organic solvents can swell PDMS significantly, seriously degrading device performance. The limited chemical compatibility of PDMS is, therefore, a major problem that can limit the wider application of PDMS to microfluidic technology. We coat PDMS microfluidic devices with a glass-like layer using sol-gel chemistry. The coating greatly increases the chemical resistance of the channels, enabling the use of organic solvents. In addition, the coating can be functionalized with a wide range of silanes, for example, to make the channels either hydrophilic or hydrophobic.

Droplet Based Microfluidics for High-Throughput Monoclonal Antibody Screening: We exploit droplet based microfluidics in order to develop a high-throughput assay for monoclonal antibody screening. We use monodisperse aqueous emulsion droplets in a continuous oil phase as picoliter-sized reaction volumes. Single antibody producing hybridoma cells are encapsulated in these drops, which serve as individual compartments. Upon incubation for several hours the cells produce monoclonal antibodies. Co-encaplsulation with beads, which are coated with a particular target antigen, leads to attachment of the primary antibodies to the surface of the beads. Successive fusion of the drops containing the cells and beads with drops containing a fluorescent secondary anti-mouse antibody leads to a concentration of fluorescence around the beads. We are able to detect this fluorescent signal and sort the drops containing cells that produce the desired antibody. Live cells can be recovered and used for monoclonal antibody production against the specified antigen.

Directed evolution of enzymes in microfluidic devices: We are recreating the mechanisms of natural selection in the laboratory at the single enzyme level. One goal is to engineer new enzyme functions using this method. These may have interesting industrial, synthetic, or therapeutic uses. In addition, In vitro evolution also gives us the ability to observe evolutionary intermediates, control selective pressure, mutation rate, and population sizes in ways that arent possible using other methods, and this allows us to ask new questions about the evolutionary process itself.

Gene expression changes in response to environmental stimuli: When genetically identical cells are exposed to the same environmental conditions, they exhibit phenotypic variation. To study the mechanisms that give rise to this variation, w**e have developed microfluidic devices to encapsulate populations of single cells. Using these devices, we can continuously flow media past the cells, vary environmental conditions, and monitor gene expression in individual cells by fluorescence microscopy. We design the chambers so that cells are constrained to grow in a single line. This makes it easy to study gene expression in single cells and their progeny. Ultimately these experiments provide insights into how patterns in gene expression are passed on to progeny cells.

SPLASHING, MOLECULAR AGGREGATION, AND EMULSION GELS
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Drop Impact: When millimeter-sized water drops impact a dry surface a variety of things can happen. Under certain conditions the drop will spread out over the surface and under other conditions the rim delaminates leading to a splash. While many groups have thought about this research, there is not yet a robust theory that can account for splashing at atmospheric conditions.

Compressional Modulus of Emulsion Gel: We study the creaming of emulsion gel under gravitation. Due to the density mismatch between oil and water, emulsions are always prone to creaming. Gelation of emulsion may be one way to control creaming.

Fluorescence Correlation Spectroscopy and Molecular Aggregation: The heavy oil reserves in northern Canada may be the largest hydrocarbon reserves on the planet. However, these oils are loaded with asphaltenes: an ambiguous chemical definition based on a solubility class. These asphaltenes are aromatic molecules with a complex phase behavior and play a crucial role in the economics of oil production all the way from extraction to transport and refining. From the stand point of physical chemistry, we would like to know more about this phase behavior, and about their interfacial and chemical properties. In order to achieve this, the first step is elemental and compositional analysis. Determination of molecular sizes or diffusivities is the second step. The next step is to understand their thermodynamics: in particular their aggregation thermodynamics and kinetics. The first condition was addressed decades ago. The second condition has been studied for roughly the same amount of time, but the results are still a matter of debate. Using Fluorescence Correlation Spectroscopy we have been able to determine an average molecular diffusivity for asphaltenes dissolved in toluene.

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