We present an approach to fabricate solid capsules with precise control of size, permeability, mechanical strength, and compatibility. The capsules are fabricated by the self-assembly of colloidal particles onto the interface of emulsion droplets. After the particles are locked together to form elastic shells, the emulsion droplets are transferred to a fresh continuous-phase fluid that is the same as that inside the droplets. The resultant structures, which we call "colloidosomes," are hollow, elastic shells whose permeability and elasticity can be precisely controlled. The generality and robustness of these structures and their potential for cellular immunoisolation are demonstrated by the use of a variety of solvents, particles, and contents.Efficient encapsulation of active ingredients such as drugs, proteins, vitamins, flavors, gas bubbles, or even living cells is becoming increasingly important for a wide variety of applications and technologies, ranging from functional foods to drug delivery to biomedical applications (1-8). Increasingly sophisticated techniques are being developed to create physical structures that can meet the demanding requirements of these applications. A versatile technique should provide efficient encapsulation in structures whose size, permeability, mechanical strength, and compatibility can be easily controlled. Control of the size allows flexibility in applications and choice of encapsulated materials; control of the permeability allows selective and timed release; control of the mechanical strength allows the yield stress to be adjusted to withstand varying of mechanical loads and to enable release by defined shear rates; and control of compatibility allows encapsulation of fragile and sensitive ingredients, such as biomolecules and cells. Precise control of all these features would allow the strategic design of possible release mechanisms. Ideally, it should be feasible to construct these capsules from a wide variety of inorganic, organic, or polymeric materials to provide flexibility in their uses.A variety of techniques has been developed to address specific encapsulation requirements: Coacervation, or controlled gelation, of polymers at the surface of water drops can be used to fabricate nano-or microporous capsules (1-5, 9); other fluid extrusion methods can also be used to create the polymer coating (6, 7). Coating immiscible templates by electrostatic deposition of alternating layers of charged polymers or particles can be used to fabricate nanoporous capsules (10-18). Microfabrication technology can be used to create submillimeter-sized silicon capsules with exquisitely precise nanometer-scale holes for selective permeability and slow release (19). However, despite the enormous progress in encapsulation technologies, these methods can be limited in their applicability, in the range of materials that can be used, in the uniformity of pore sizes, in the accessible permeabilities and elasticities, or in the ease of synthesis, filling efficiency, and yield. We present a flexi...

The surface plasmon resonance peaks of gold nanostructures can be tuned from the visible to the near infrared region by controlling the shape and structure (solid vs. hollow). In this tutorial review we highlight this concept by comparing four typical examples: nanospheres, nanorods, nanoshells, and nanocages. A combination of this optical tunability with the inertness of gold makes gold nanostructures well suited for various biomedical applications.

The explosive growth in our knowledge of genomes, proteomes, and metabolomes is driving ever-increasing fundamental understanding of the biochemistry of life, enabling qualitatively new studies of complex biological systems and their evolution. This knowledge also drives modern biotechnologies, such as molecular engineering and synthetic biology, which have enormous potential to address urgent problems, including developing potent new drugs and providing environmentally friendly energy. Many of these studies, however, are ultimately limited by their need for even-higher-throughput measurements of biochemical reactions. We present a general ultrahigh-throughput screening platform using drop-based microfluidics that overcomes these limitations and revolutionizes both the scale and speed of screening. We use aqueous drops dispersed in oil as picoliter-volume reaction vessels and screen them at rates of thousands per second. To demonstrate its power, we apply the system to directed evolution, identifying new mutants of the enzyme horseradish peroxidase exhibiting catalytic rates more than 10 times faster than their parent, which is already a very efficient enzyme. We exploit the ultrahigh throughput to use an initial purifying selection that removes inactive mutants; we identify ∼100 variants comparable in activity to the parent from an initial population of ∼10 7 . After a second generation of mutagenesis and high-stringency screening, we identify several significantly improved mutants, some approaching diffusion-limited efficiency. In total, we screen ∼10 8 individual enzyme reactions in only 10 h, using < 150 μL of total reagent volume; compared to state-of-the-art robotic screening systems, we perform the entire assay with a 1,000-fold increase in speed and a 1-million-fold reduction in cost.

We report a method to generate steady coaxial jets of immiscible liquids with diameters in the range of micrometer/nanometer size. This compound jet is generated by the action of electro-hydrodynamic (EHD) forces with a diameter that ranges from tens of nanometers to tens of micrometers. The eventual jet breakup results in an aerosol of monodisperse compound droplets with the outer liquid surrounding or encapsulating the inner one. Following this approach, we have produced monodisperse capsules with diameters varying between 10 and 0.15 micrometers, depending on the running parameters.

The precision manipulation of streams of fluids with microfluidic devices is revolutionizing many fluid-based technologies and enabling the development of high-throughput reactors that use minute quantities of reagents. However, as the scale of these reactors shrinks, contamination effects due to surface adsorption and diffusion limit the smallest quantities that can be used. The confinement of reagents in droplets in an immiscible carrier fluid overcomes these limitations, but demands new fluid-handling technology. We present a platform technology based on charged droplets and electric fields that enables electrically addressable droplet generation, highly efficient droplet coalescence, precision droplet breaking and recharging, and controllable droplet sorting. This is an essential enabling technology for a high-throughput droplet microfluidic reactor.Networks of small channels are a flexible platform for the precision manipulation of small amounts of fluids. [1,2] The utility of such microfluidic devices depends critically on enabling technologies such as the microfluidic peristaltic pump, [3] electrokinetic pumping, [4,5] and dielectrophoreticpump or electrowetting-driven [6] flow; these technologies can form the essential building blocks for the assembly of fluidhandling modules.[7] These modules can be used to perform a variety of key tasks including the measurement of precise aliquots of fluids, the combination of fluid streams, and the mixing of multiple fluid components. The assembly of such modules into complete systems provides a convenient and robust way to construct microfluidic devices. These have myriad uses; for example, high-throughput screening, [8] the exploration of chemical phase diagrams, assays of biological molecules, [9][10][11] single-cell analysis, [12][13][14][15][16][17] and combinatorial approaches to protein crystallization [18] can all be performed with only minimal consumption of reagents. However, virtually all microfluidic devices are based on flows of streams of fluids; this sets a limit on the smallest volume of reagent that can be used effectively because of the contaminating effects of diffusion and surface adsorption. As the dimensions of small volumes are decreased, diffusion becomes the dominant mechanism for mixing leading to dispersion of reactants. Moreover, surface adsorption of reactants, although small, can be highly detrimental at low concentrations and small volumes. As a result current microfluidic technologies cannot be reliably used for applications involving minute quantities of reagent-for example, bioassays at levels down to the single molecule are not easily performed. An approach that overcomes these limitations is the use of aqueous droplets in an immiscible carrier fluid; [19] these droplets provide a well-defined, encapsulated microenvironment that eliminates cross-contamination or changes in concentration caused by diffusion or surface interactions. Droplets provide the ideal microcapsule that can isolate reactive materials, cells, or small particles f...

Solid state materials capable of storing hydrogen with high gravimetric (9 wt %) and volumetric density (70 g/L) are critical for the success of a new hydrogen economy. In addition, an ideal storage system should be able to operate under ambient thermodynamic conditions and exhibit fast hydrogen sorption kinetics. No materials are known that meet all these requirements. While recent theoretical efforts showed some promise for transition-metal-coated carbon fullerenes, later studies demonstrated that these metal atoms prefer to cluster on the fullerene surface, thus reducing greatly the weight percentage of stored hydrogen. Using density functional theory we show that Li-coated fullerenes do not suffer from this constraint. In particular, we find that an isolated Li(12)C(60) cluster where Li atoms are capped onto the pentagonal faces of the fullerene not only is very stable but also can store up to 120 hydrogen atoms in molecular form with a binding energy of 0.075 eV/H(2). In addition, the structural integrity of Li(12)C(60) clusters is maintained when they are allowed to interact with each other. The lowest energy structure of the dimer is one where the Li atom capped on the five-member ring of one fullerene binds to the six-member ring of the other. The binding of hydrogen to the linking Li atom and the potential of materials composed of Li(12)C(60) building blocks for hydrogen storage are discussed.

This paper describes a two-step procedure for generating cubic nanocages and nanoframes. In the first step, Au/Ag alloy nanoboxes were synthesized through the galvanic replacement reaction between Ag nanocubes and an aqueous HAuCl 4 solution. The second step involved the selective removal (or dealloying) of Ag from the alloy nanoboxes with an aqueous etchant based on Fe (NO 3 ) 3 or NH 4 OH. The use of a wet etchant other than HAuCl 4 for the dealloying process allows one to better control the wall thickness and porosity of resultant nanocages because there is no concurrent deposition of Au. By increasing the amount of Fe(NO 3 ) 3 or NH 4 OH added to the dealloying process, nanoboxes derived from 50-nm Ag nanocubes could be converted into nanocages and then cubic nanoframes with surface plasmon resonance (SPR) peaks continuously shifted from the visible region to 1200 nm. It is also possible to obtain nanocages with relatively narrow SPR peaks (with an FWHM as small as 180 nm) by controlling the amount of HAuCl 4 used for the galvanic replacement reaction and thus optimization of the percentage of Au in the alloy nanoboxes.Hollow nanoparticles of noble metals have unique physical and chemical characteristics that differentiate them from many other types of nanostructured materials. 1 They have also been recognized for a range of applications, including catalysis, 2 optical sensing, 3 drug delivery, 4 biomedical imaging, 5 as well as photothermal cancer treatment. 6 Among various synthetic routes, the one based on galvanic replacement reaction has proven to be the most effective in generating hollow nanostructures from a number of noble metals. 1,7 It has been demonstrated that bimetallic alloy hollow nanostructures composed of Ag and Au, Pd, or Pt could be conveniently prepared by reacting Ag nanostructures with a compound containing a less reactive noble metal such as Au, Pd, or Pt. In particular, Au/Ag nanoboxes (nanostructures with hollow interiors) and nanocages (nanostructures with hollow interiors and porous walls) with tunable surface plasmon resonance (SPR) peaks can be routinely synthesized by reacting Ag nanocubes with HAuCl 4 in an aqueous solution. By increasing the amount of HAuCl 4 added to a suspension of Ag nanocubes, the nanocubes can be controlled to evolve from solid objects into cubic nanoboxes and then nanocages. As a well-established example, the SPR peaks of *Corresponding author. E-mail: xia@chem.washington.edu. gold hollow nanoboxes and nanocages can be readily tuned from the visible to the near-infrared (NIR) region by varying the wall thickness relative to the overall dimension. 8 NIH Public AccessAlthough the protocol based on the galvanic replacement reaction with HAuCl 4 works well for Ag nanostructures of a variety of shapes, it has a drawback that limits our ability to achieve a tight control over the wall thickness and porosity for the resultant nanocages. In the early stage of the reaction (or when a relatively small amount of HAuCl 4 is added), Ag atoms are dissolved fr...

The use of microfluidic devices to control drops of water in a carrier oil is a promising means of performing biological and chemical assays. An essential requirement for this is the controlled coalescence of pairs of drops to mix reagents together. We show that this can be accomplished through electrocoalescence of drops synchronized by size-dependent flow in microfluidic channels. Smaller drops move faster due to the Poiseuille flow, allowing pairs of surfactant-stabilized drops to be brought into contact where they are coalesced with an electric field. We apply this method to an enzyme assay to measure enzyme kinetic constants.