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Showing papers by "George M. Whitesides published in 2005"




Journal ArticleDOI
TL;DR: A versatile new strategy for producing monodisperse solid particles with sizes from 20 to 1000 mm by using a microfluidic device and shaping the droplets in a microchannel and then solidifying these drops in situ either by polymerizing a liquid monomer or by lowering the temperature of a liquid that sets thermally.
Abstract: Herein we describe a versatile new strategy for producing monodisperse solid particles with sizes from 20 to 1000 mm. The method involves the formation of monodisperse liquid droplets by using a microfluidic device and shaping the droplets in a microchannel and then solidifying these drops in situ either by polymerizing a liquid monomer or by lowering the temperature of a liquid that sets thermally. This method has the following features: 1) It produces particles with an exceptionally narrow range of sizes. 2) A new level of control over the shapes of the particles is offered. 3) The mechanism for droplet formation allows the use of a wide variety of materials including gels, metals, polymers, and polymers doped with functional additives. 4) The procedure can be scaled up to produce large numbers of particles. A number of methods exist for making inorganic and organic particles with narrow polydispersity. Inorganic colloids are typically prepared by precipitation reactions from organometallic precursors. Polymer colloids with sizes from 20 nm to approximately 1 mm are usually prepared by a variation of emulsion polymerization techniques. Larger beads are accessible through miniemulsion polymerization,

882 citations


Journal ArticleDOI
01 Feb 2005-Small
TL;DR: “Nanoscience” is the emerging science of objects that are intermediate in size between the largest molecules and the smallest structures that can be fabricated by current photolithography; that is, thescience of objects with smallest dimensions ranging from a few nanometers to less than 100 nanometers.
Abstract: “Nanoscience” is the emerging science of objects that are intermediate in size between the largest molecules and the smallest structures that can be fabricated by current photolithography; that is, the science of objects with smallest dimensions ranging from a few nanometers to less than 100 nanometers. In chemistry, this range of sizes has historically been associated with colloids, micelles, polymer molecules, phase-separated regions in block copolymers, and similar structures—typically, very large molecules, or aggregates of many molecules. More recently, structures such as buckytubes, silicon nanorods, and compound semiconductor quantum dots have emerged as particularly interesting classes of nanostructures. In physics and electrical engineering, nanoscience is most often associated with quantum behavior, and the behavior of electrons and photons in nanoscale structures. Biology and biochemistry also have a deep interest in nanostructures as components of the cell; many of the most interesting structures in biology—from DNA and viruses to subcellular organelles and gap junctions—can be considered as nanostructures. These very small structures are intensely interesting for many reasons. First, many of their properties mystify us. How does the flagellar motor of E. coli run? How do electrons move through organometallic nanowires? Second, they are challenging to make. Molecules are easily synthesized in large quantities, and can be characterized thoroughly. Colloids and micelles and crystal nuclei have always been more difficult to prepare (in fact, most can only be made as mixtures—a characteristic that contributes to the difficulty of colloid science) and to characterize; developing a “synthetic chemistry” of colloids that is as precise as that used to make molecules is a wonderful challenge for chemistry. Synthesizing or fabricating ordered arrays and patterns of colloids poses a different and equally fascinating set of problems. Third, because many nanoscale structures have been inaccessible and/or off the beaten scientific track, studying these structures leads to new phenomena. Very small particles, or large, ordered, aggregates of molecules or atoms, are simply not structures that science has been able to explore carefully. Fourth, nanostructures are in a range of sizes in which quantum phenomena—especially quantum entanglement and other reflections of the wave character of matter—would be expected to be important (and important at room temperature!). Quantum phenomena are, of course, the ultimate basis of the properties of atoms and molecules, but are largely hidden behind classical behavior in macroscopic matter and structures. Quantum dots and nanowires have already been prepared and demonstrated to show remarkable electronic properties; there will, I am certain, be other nanoscale materials, and other properties, to study and exploit. Fifth, the nanometer-sized, functional structures that carry out many of the most sophisticated tasks of the cell are one frontier of biology. The ribosome (Figure 1), histones and chromatin, the Golgi apparatus, the interior structure of the mitochondrion, the flagellar micromotor, the photosynthetic reaction center, and the fabulous ATPases that power the cell are all nanostructures we have only just begun to understand. Sixth, nanostructures will be the basis of nanoelectronics and -photonics. The single most important fabrication technology of our time is, arguably, microlithography: its progeny—the microprocessors and memories that it generates—are the basis for the information technology that has so transformed society in the last half-century (Figure 2). Microelectronic technology has relentlessly followed a single law—Moore s law—for almost 50 years; the popular expression of this law is “smaller is cheaper and faster”. 21] Enthusiasm for “smaller” as the guiding ideology in circuit design has recently cooled, and other features—heat dissipation, power distribution, clock synchronization, intrachip communication—have become increasingly important. Still, technical evolution in the semiconductor industry has brought the components of [*] Prof. G. M. Whitesides Department of Chemistry and Chemical Biology Harvard University Cambridge MA 02138 (USA) Fax: (+1) 617-495-9857 E-mail: gwhitesides@gmwgroup.harvard.edu

594 citations


Journal ArticleDOI
TL;DR: This Letter describes a quasistationary breakup of an immiscible, inviscid fluid at low capillary numbers, which forms the basis for controlled, high-throughput generation of monodisperse fluid dispersions.
Abstract: This Letter describes a quasistationary breakup of an immiscible, inviscid fluid at low capillary numbers. The breakup proceeds in a coflowing, viscous liquid, in a confined geometry of a long and narrow orifice. In contrast to the capillary instability in an unbounded fluid, the collapse proceeds through a series of equilibria, each yielding the minimum interfacial energy of the fluid-fluid interface. The process is slow in comparison to typical relaxation speeds of the interface, and it is reversible. Its quasistatic character of collapse forms the basis for controlled, high-throughput generation of monodisperse fluid dispersions.

574 citations


Journal ArticleDOI
TL;DR: It is shown that the direction of polarization of attached mammalian cells determines the direction in which they move.
Abstract: This report shows that the direction of polarization of attached mammalian cells determines the direction in which they move. Surfaces micropatterned with appropriately functionalized self-assembled monolayers constrain individual cells to asymmetric geometries (for example, a teardrop); these geometries polarize the morphology of the cell. After electrochemical desorption of the self-assembled monolayers removes these constraints and allows the cells to move across the surface, they move toward their blunt ends.

456 citations


Journal ArticleDOI
30 Jun 2005-Nature
TL;DR: It is proposed that when cells are confined between two interfaces—one an agar gel and the second PDMS—they swim closer to the agar surface than to the PDMS surface, leading to the preferential movement on the right of the microchannel, and the choice of materials guides the motion of cells in microchannels.
Abstract: The motion of peritrichously flagellated bacteria close to surfaces is relevant to understanding the early stages of biofilm formation and of pathogenic infection. This motion differs from the random-walk trajectories of cells in free solution. Individual Escherichia coli cells swim in clockwise, circular trajectories near planar glass surfaces. On a semi-solid agar substrate, cells differentiate into an elongated, hyperflagellated phenotype and migrate cooperatively over the surface, a phenomenon called swarming. We have developed a technique for observing isolated E. coli swarmer cells moving on an agar substrate and confined in shallow, oxidized poly(dimethylsiloxane) (PDMS) microchannels. Here we show that cells in these microchannels preferentially 'drive on the right', swimming preferentially along the right wall of the microchannel (viewed from behind the moving cell, with the agar on the bottom). We propose that when cells are confined between two interfaces--one an agar gel and the second PDMS--they swim closer to the agar surface than to the PDMS surface (and for much longer periods of time), leading to the preferential movement on the right of the microchannel. Thus, the choice of materials guides the motion of cells in microchannels.

432 citations


Journal ArticleDOI
TL;DR: In this article, the authors proposed a method to use the 3.3% ratio of the ratio of 2.5% to 3% of the 3% in order to measure the quality of a user's interaction with a service provider.
Abstract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

376 citations


Journal ArticleDOI
TL;DR: This study presents a method for harnessing the power produced by biological motors that uses intact cells and uses unicellular, biflagellated algae Chlamydomonas reinhardtii as "microoxen".
Abstract: It is difficult to harness the power generated by biological motors to carry out mechanical work in systems outside the cell. Efforts to capture the mechanical energy of nanomotors ex vivo require in vitro reconstitution of motor proteins and, often, protein engineering. This study presents a method for harnessing the power produced by biological motors that uses intact cells. The unicellular, biflagellated algae Chlamydomonas reinhardtii serve as "microoxen." This method uses surface chemistry to attach loads (1- to 6-microm-diameter polystyrene beads) to cells, phototaxis to steer swimming cells, and photochemistry to release loads. These motile microorganisms can transport microscale loads (3-microm-diameter beads) at velocities of approximately 100-200 microm.sec(-1) and over distances as large as 20 cm.

356 citations


Journal ArticleDOI
01 Jul 2005-Small
TL;DR: This manuscript describes the use of water-soluble polymers for use as sacrificial layers in surface micromachining, compatible with a number of fragile materials, such as organic polymers, metal oxides and metals-materials that might be damaged during typical surface micronachining processes.
Abstract: This manuscript describes the use of water-soluble polymers for use as sacrificial layers in surface micromachining. Water-soluble polymers have two attractive characteristics for this application: 1) They can be deposited conveniently by spin-coating, and the solvent removed at a low temperature (95-150 degrees C), and 2) the resulting layer can be dissolved in water; no corrosive reagents or organic solvents are required. This technique is therefore compatible with a number of fragile materials, such as organic polymers, metal oxides and metals-materials that might be damaged during typical surface micromachining processes. The carboxylic acid groups of one polymer-poly(acrylic acid) (PAA)-can be transformed by reversible ion-exchange from water-soluble (Na+ counterion) to water-insoluble (Ca2+ counterion) forms. The use of PAA and dextran polymers as sacrificial materials is a useful technique for the fabrication of microstructures: Examples include metallic structures formed by the electrodeposition of nickel, and freestanding, polymeric structures formed by photolithography.

278 citations



Journal ArticleDOI
TL;DR: A simple and reliable technique for storing and delivering a sequence of reagents to a microfluidic device, which is low-cost, requires minimal user intervention, and can be performed in resource-poor settings in the absence of electricity and computer-controlled equipment.
Abstract: An important problem in the life sciences and in health care is simple and rapid detection of biomarkers. Although microfluidic devices are potentially useful in addressing this problem, current techniques for automating fluid deliverywhich include valves and electroosmosisrequire sophisticated microfabrication of the chip, bulky instrumentation, or both. In this paper, we describe a simple and reliable technique for storing and delivering a sequence of reagents to a microfluidic device. The technique is low-cost, requires minimal user intervention, and can be performed in resource-poor settings (e.g., outside of a laboratory) in the absence of electricity and computer-controlled equipment. In this method, cartridges made of commercially available tubing are filled by sequentially injecting plugs of reagents separated by air spacers. The air spacers prevent the reagents from mixing with each other during cartridge preparation, storage, and usage. As an example, we used this “plug-in cartridge” technology ...

Journal ArticleDOI
TL;DR: These valves have the useful characteristic that they do not require power to retain their setting (on/off) and can be integrated into portable, disposable microfluidic devices for carrying out sandwich immunoassays.
Abstract: This paper describes torque-actuated valves for controlling the flow of fluids in microfluidic channels. The valves consist of small machine screws (≥500 μm) embedded in a layer of polyurethane cast above microfluidic channels fabricated in poly(dimethylsiloxane) (PDMS). The polyurethane is cured photochemically with the screws in place; on curing, it bonds to the surrounding layer of PDMS and forms a stiff layer that retains an impression of the threads of the screws. The valves were separated from the ceiling of microfluidic channels by a layer of PDMS and were integrated into channels using a simple procedure compatible with soft lithography and rapid prototyping. Turning the screws actuated the valves by collapsing the PDMS layer between the valve and channel, controlling the flow of fluids in the underlying channels. These valves have the useful characteristic that they do not require power to retain their setting (on/off). They also allow settings between “on” and “off” and can be integrated into po...

Journal ArticleDOI
TL;DR: This report describes the spontaneous folding of flat elastomeric sheets, patterned with magnetic dipoles, into free-standing, 3D objects that are the topological equivalents of spherical shells.
Abstract: This report describes the spontaneous folding of flat elastomeric sheets, patterned with magnetic dipoles, into free-standing, 3D objects that are the topological equivalents of spherical shells. The path of the self-assembly is determined by a competition between mechanical and magnetic interactions. The potential of this strategy for the fabrication of 3D electronic devices is demonstrated by generating a simple electrical circuit surrounding a spherical cavity.

Journal ArticleDOI
TL;DR: In this paper, a mesoscale self-assembly method is proposed to fabricate hard-to-fabricate structural components using mesoscaling self-assembling components.
Abstract: Self-assembly—the spontaneous generation of order in systems of components—is ubiquitous in chemistry; in biology, it generates much of the functionality of the living cell. Self-assembly is relatively unused in microfabrication, although it offers opportunities to simplify processes, lower costs, develop new processes, use components too small to be manipulated robotically, integrate components made using incompatible technologies, and generate structures in three dimensions and on curved surfaces. The major limitations to the self-assembly of micrometer- to millimeter-sized components (mesoscale self-assembly) do not seem to be intrinsic, but rather operational: selfassembly can, in fact, be reliable and insensitive to small process variations, but fabricating the small, complex, functional components that future applications may require will necessitate the development of new methodologies. Proof-of-concept experiments in mesoscale self-assembly demonstrate that this technique poses fascinating scientific and technical challenges and offers the potential to provide access to hard-to-fabricate structures.

Journal ArticleDOI
TL;DR: A technique for growing filamentous cells of Escherichia coli with defined shapes, including crescents, zigzags, sinusoids, and spirals is described, which grows into a multinucleate, nonseptate, filamentous phenotype and adopt the shape of the microchambers.
Abstract: This paper describes a technique for growing filamentous cells of Escherichia coli with defined shapes, including crescents, zigzags, sinusoids, and spirals. The procedure begins with the fabrication of embossed microchambers in agarose. Cells are trapped in the chambers by placing a flat, flexible “ceiling”, either a slab of agarose or poly(dimethylsiloxane), against an agarose mold on which a suspension of cells has been added; the use of agarose keeps cells hydrated and allows nutrients to diffuse into the chambers. Cells grown in microchambers in the presence of cephalexin grow into a multinucleate, nonseptate, filamentous phenotype and adopt the shape of the microchambers. The resulting cells are motile and can be released by removing the “ceiling” from the agarose microchambers and rinsing the cells into solution.

Journal ArticleDOI
TL;DR: A microfluidic network is utilizes that generates a gradient of avidin in solution and immobilizes this protein on the surface of glass or poly(dimethylsiloxane) by physical adsorption to fabrication of immobilized gradients of biomolecules on surfaces.
Abstract: This report outlines a general method for the fabrication of immobilized gradients of biomolecules on surfaces. This method utilizes a microfluidic network that generates a gradient of avidin in solution and immobilizes this protein on the surface of glass or poly(dimethylsiloxane) by physical adsorption. The immobilized gradient of avidin is then translated into gradients of biotinylated ligands (e.g., small molecules, oligomers of DNA, polysaccharides) using the specific interaction between biotin and avidin. This method can also generate immobilized gradients of certain proteins and artificial polymers by a direct transfer of gradients from solution onto the surface. The major advantage of this method is that almost any type of molecule can, in principle, be immobilized in a well-defined surface gradient of arbitrary shape with dimensions of a few micrometers to a few centimeters. It is possible to tailor the precise shapes of gradients on surfaces from gradients in solution, either kinetically or comp...

Journal ArticleDOI
TL;DR: This device provides a simple, high intensity, tunable light source for microfludic applications and the output wavelength was tunable over a 20-nm range by changing the ratio of solvent components in the liquid core.
Abstract: This communication describes a long (1 cm), laser-pumped, liquid core-liquid cladding (L2) waveguide laser. This device provides a simple, high intensity, tunable light source for microfludic applications. Using a core solution of 2 mM rhodamine 640 perchlorate, optically pumped by a frequency-doubled Nd:YAG laser, we found that the threshold for lasing was as low as 22 muJ (16-ns pulse length) and had a slope efficiency up to 20%. The output wavelength was tunable over a 20-nm range by changing the ratio of solvent components (dimethyl sulfoxide and methanol) in the liquid core.

Journal ArticleDOI
TL;DR: Direct stamping of human osteoblasts can be used to control the size, spacing, and geometry of patterns of cells printed on porous tissue engineering substrates and may find use in controlling the spatial invasion of scaffolds, promoting the hierarchical organization of cells, and in controlling cell-cell interactions as a step in preservation of phenotypes of cells.

Journal ArticleDOI
TL;DR: This perspective discusses some of the technical issues - potential functions, protein plasticity, enthalpy/entropy compensation, and others - that contribute, and suggests areas where fundamental understanding of protein-ligand interactions falls short of what is needed.
Abstract: The ability to design drugs (so-called 'rational drug design') has been one of the long-term objectives of chemistry for 50 years. It is an exceptionally difficult problem, and many of its parts lie outside the expertise of chemistry. The much more limited problem - how to design tight-binding ligands (rational ligand design) - would seem to be one that chemistry could solve, but has also proved remarkably recalcitrant. The question is 'Why is it so difficult?' and the answer is 'We still don't entirely know'. This perspective discusses some of the technical issues - potential functions, protein plasticity, enthalpy/entropy compensation, and others - that contribute, and suggests areas where fundamental understanding of protein-ligand interactions falls short of what is needed. It surveys recent technological developments (in particular, isothermal titration calorimetry) that will, hopefully, make now the time for serious progress in this area. It concludes with the calorimetric examination of the association of a series of systematically varied ligands with a model protein. The counterintuitive thermodynamic results observed serve to illustrate that, even in relatively simple systems, understanding protein-ligand association is challenging.

Journal ArticleDOI
TL;DR: Experimental observations support inertia-dominated dynamics of the interface, and suggest the possible similarity to the dynamics of a topologically inverted counterpart of this system, that is, a dripping faucet.
Abstract: We describe the rich dynamic behavior--including period-doubling and period-halving bifurcations, intermittency, and chaos--observed in the breakup of an inviscid fluid in a coflowing, viscous liquid, both confined in a microfabricated flow-focusing geometry. Experimental observations support inertia-dominated dynamics of the interface, and suggest the possible similarity to the dynamics of a topologically inverted counterpart of this system, that is, a dripping faucet.

Journal ArticleDOI
08 Apr 2005-Langmuir
TL;DR: Micropatterned agarose stamps prepared by molding against PDMS masters to print patterns of bacteria on agar plates are described, which are rapid, reproducible, convenient, and can be used to control the pattern, spacing, and orientation between colonies of different bacteria.
Abstract: This paper describes the use of micropatterned agarose stamps prepared by molding against PDMS masters to print patterns of bacteria on agar plates. Topographically patterned agarose stamps were inked with suspensions of bacteria; these stamps generated patterns of bacteria with features as small as 200 microm over areas as large as 50 cm2. Stamps with many small features (>200 microm) were used to study patterns of bacteria growing on media containing gradients of small molecules; stamps with larger features (>750 microm) were used to print different strains of bacteria simultaneously. The stamp transfers only a small percentage of cells that are on its surface to the agar at a time; it is thus possible to replica-pattern hundreds of times with a single inking. The use of soft stamps provides other useful functions. Stamps are easily customized to provide a range of patterns. When culture media is included in the agarose stamp, cells divide and thrive on the surface. The resulting "living stamp" regenerates its "ink" and can be used to pattern surfaces repetitively for a month. This method is rapid, reproducible, convenient, and can be used to control the pattern, spacing, and orientation between colonies of different bacteria.

Journal ArticleDOI
TL;DR: Understanding the principles by which monolayers form, and connecting molecular-level structure with macroscopic properties, opens a wide range of areas to study and exploitation.
Abstract: The self-assembly of molecules into structurally organized monolayers (SAMs) uses the flexibility of organic chemistry and coordination chemistry to generate well-defined, synthetic surfaces with known molecular and macroscopic properties The process of designing monolayers with a specified structure gives a high level of control over the molecular-level composition in the direction perpendicular to a surface; soft lithographic technique gives useful (if lower) resolution in the plane of the surface Alkanethiolates adsorbed on gold, silver, mercury, palladium and platinum are currently the best-defined systems of SAMs They provide substrates for a number of applications-from studies of wetting and electron transport to patterns for growing mammalian cells SAMs have made organic surfaces a central part of surface science Understanding the principles by which they form, and connecting molecular-level structure with macroscopic properties, opens a wide range of areas to study and exploitation

Journal ArticleDOI
TL;DR: Recent advances in materials science are discussed that provide well-defined physical environments that can be used to study cells, both individually and in groups, in attached culture and the challenges that must be addressed in order to make cell-based assays reproducible.
Abstract: Assays based on observations of the biological responses of individual cells to their environment have the potential to make enormous contributions to cell biology and biomedicine.To carry out well-defined experiments using cells, both the environments in which the cells live and the cells themselves must be well defined. Cell-based assays are now plagued by inconsistencies and irreproducibility, and a primary challenge in the development of informative assays is to understand the fundamental bases for these inconsistencies and to limit them. It now seems that multiple factors may contribute to the variability in the response of individual cells to stimuli; some of these factors may be extrinsic to the cells, some intrinsic. New techniques based on microengineering—especially using soft lithography to pattern surfaces at the molecular level and to fabricate microfluidic systems—have provided new capabilities to address the extrinsic factors. This review discusses recent advances in materials science that provide well-defined physical environments that can be used to study cells, both individually and in groups, in attached culture. It also reviews the challenges that must be addressed in order to make cell-based assays reproducible.

Journal ArticleDOI
TL;DR: By controlling the ratio of nitrogen to oxygen in the source gas as used in the CVD method, the ultimate nitrogen, carbon and fluorine concentrations in the film can be controlled and hence the dielectric constant of the film so produced is controlled.
Abstract: This paper describes a simple method for the microfabrication of mechanically compliant, magnetically-responsive microstructures. These microstructures were fabricated in one step by using a ferromagnetic photoresist, which, in turn, was prepared by suspending nickel nanospheres in a negative photosensitive epoxy (SU8). The nominal diameter of the nickel nanospheres was 80–150 nm, that is, much smaller than the wavelength of the UV light (365 and 405 nm) used to expose the photoresist. Diffraction and scattering of light from the nanospheres allowed for full exposure of the photoresist, even after the incorporation of nanospheres at levels at which it became opaque. The ferromagnetic photoresist was cross-linked after exposure and development, and yielded a stable, compliant, ferromagnetic pattern. The paper characterizes the effect of the weight density of the nickel nanospheres on the transmittance of films made by this technique at wavelengths from 330 nm to 610 nm. It also describes a number of microstructures made with the photoresist: examples include lines, posts and meshes. As a demonstration, the procedure was applied to the microfabrication of a set of magnetically-actuated micromirrors. These micromirrors achieved large deflections: deflection at the tip of a 12 mm long, 250 µ mw ide and 70 µm thick cantilever of the ferromagnetic photoresist exceeded 1.4 mm, when actuated by a NbFeB permanent magnet with field strength ∼120 mT. The cantilever maintained its mechanical properties after cycling ∼10 6 times. S This article has online supplementary material


Journal ArticleDOI
TL;DR: In this paper, a method for producing chaotic transport trajectories in planar, microfluidic networks prepared by standard, single-step lithography and operated with a steady-state inflow of the fluids into the device is described.
Abstract: This letter describes a method for producing chaotic transport trajectories in planar, microfluidic networks prepared by standard, single-step lithography and operated with a steady-state inflow of the fluids into the device. Gaseous slugs flowing through the network produce temporal variation of pressure distribution and lead to stretching and folding of the continuous fluid. Stabilization of the bubbles by surface-active agents is not necessary, and the method is compatible with the wide range of reactions performed in on-chip bioassays.

Journal ArticleDOI
TL;DR: In this paper, the authors describe a simple fluidic light source for use on-chip in integrated microsystems, and demonstrate the feasibility of light sources based on liquid core, liquid-cladding (L2) microchannel waveguides, with liquid cores containing fluorescent dyes.
Abstract: This letter describes a simple fluidic light source for use “on-chip” in integrated microsystems. It demonstrates the feasibility of light sources based on liquid-core, liquid-cladding (L2) microchannel waveguides, with liquid cores containing fluorescent dyes. These fluorescent light sources, using both miscible and two-phase systems, are tunable in terms of the beam size, intensity and spectral content. The observed output intensity from fluorescent L2 light sources is comparable to standard fiber optic spectrophotometer light sources. Integration of fluorescent light sources during device fabrication removes both the need for insertion and alignment of conventional, optical-fiber light sources and the constraints on channel size imposed by fiber optics, albeit at the cost of establishing a microfluidic infrastructure.

Book ChapterDOI
01 Jan 2005
TL;DR: Self-assembly of nanostructured materials holds promise as a low-cost, high-yield technique with a wide range of scientific and technological applications as mentioned in this paper, which can, in principle, be made using both top-down and bottom-up techniques and allows materials to be designed with hierarchical order and complexity that mimics those seen in biological systems.
Abstract: "Nanostructured materials" are those having properties defined by features smaller than 100 nm. This class of materials is interesting for the reasons: i) They include most materials, since a broad range of properties-from fracture strength to electrical conductivitydepend on nanometer-scale features. ii) They may offer new properties: The conductivity and stiffness of buckytubes, and the broad range of fluorescent emission of CdSe quantum dots are examples. iii) They can mix classical and quantum behaviors. iv) They offer a bridge between classical and biological branches of materials science. v) They suggest approaches to "materials-by-design". Nanomaterials can, in principle, be made using both top-down and bottom-up techniques. Self-assembly bridges these two techniques and allows materials to be designed with hierarchical order and complexity that mimics those seen in biological systems. Self-assembly of nanostructured materials holds promise as a low-cost, high-yield technique with a wide range of scientific and technological applications.

Journal ArticleDOI
TL;DR: In this article, a simple microfluidic bubble generator that produces stable oscillatory patterns (both in space and time) of unanticipated complexity and uniquely long repetition periods is demonstrated.
Abstract: Understanding spatiotemporal complexity1,2,3 is important to many disciplines, from biology4,5 to finance6. However, because it is seldom possible to achieve complete control over the parameters that determine the behaviour of real complex systems, it has been difficult to study such behaviour experimentally. Here we demonstrate a simple microfluidic bubble generator that shows stable oscillatory patterns (both in space and time) of unanticipated complexity and uniquely long repetition periods. At low flow rates, the device produces a regular stream of bubbles of uniform size. As the flow increases, the system shows intricate dynamic behaviour typified by a stable limit cycle of order 29 bubbles per period, which repeats without change over intervals of up to 100 periods and more. As well as providing an example of a well-characterized and experimentally tractable model system with which to study complex, nonlinear dynamics, such behaviour demonstrates that it is possible to observe complex and stable limit cycles without active external control.