EFTA02444651.pdf

Whitesides Group - Research Page 1 of 7 The Whitesides Research Group SIMMS Research Microfluidics The Whitesides Group is very active in microfluidics. Our previous accomplishments in the field include work on laminar flow in microchannels (Figures 1,2), fabrication of three-dimensional channel topologies (Figures 3) and mixing by chaotic advection (Figure 4). We have also applied microfluidics to fabricate monodisperse polymer, hydrogel, and metal microparticles coated with thin, nylon- coated membranes (Figure 5). Currently, we are working on several projects related to microfluidics, including exploiting the behavior of bubbles and droplets for mixing Figure 1 and other applications, manipulating samples electrokinetically and probing the use of solder as electrodes in microchannels. Bubbles and Droplets in Microchannels Our recent experiments in microfluidics include investigations into the behavior of bubbles and droplets in microchannels. Specifically, we are interested in four sub- areas: (I) enhanced mixing in microfluidic systems using bubbles; (2) the paths from monodisperse to chaotic Figure 2 bubbling in flow-focusing devices; (3) the production of bubbles with uniquely high periodicities in modified flow- focusing systems; (4) the path-selection process that bubbles demonstrate as they move through a network. Mixing in microchannels, in particular, is an important challenge in the microfluidics subgroup of our laboratory (the other areas introduced here are described further in the complexity section of the website). Mixing between streams of fluid that flow in a laminar fashion is difficult to achieve. Previously, we have introduced a method to enhance mixing involving multiple lithographic steps. Our current work uses bubbles to Figure 3 facilitate the folding over of streams of fluid as they proceed through a network of microchannels (Movie 6). The bubbles partially block the channels in which they move, causing a portion of a stream of bulk fluid to cross over into the http://gmwgroup.harvard.edu/research_microfluidics.html 11/6/2008 EFTA_R1_015215843 EFTA02444651 Whitesides Group - Research Page 2 of 7 channel in which the other stream moves. This process is repeated several times before the streams are mixed fully, with the final mixing device occupying an area of only a square millimeter on the chip. -stasktA V2 cycle Electrokinetic Flow in Microfluidic Channels Itaal We are exploring electrokinetically-driven microfluidic systems for separation of complex biological samples. Our Figure 4 ultimate goal is to provide a new sample handling method (femtomole/nL) for proteomic analysis and high-throughput -• biochemical assays. Currently, we are investigating - • geometrical designs, surface coatings and concentration techniques such as isotachophoresis. - •-• •-• ••• O'N TWIST Valves 3•N L. JINN We have developed a new approach for controlling the flow 7 C-47-r eckti of fluids in microfluidic channels. TWIST valves consist of small machine screws (500 um diameter) embedded in a Figure 5 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 (Figure 7). The valves are separated from the ceiling of microfluidic channels by a layer of PDMS, and are integrated into channels using a simple procedure compatible with rapid prototyping. Turning the screws actuates 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 Movie 6 their setting (on/off). They also allow settings between "on" and "off', resist large back pressures (>350 kPa) without failure, and can be integrated into portable, disposable microfluidic devices for carrying out biological assays Int (Figure 8). TWIST Pumps We have designed a system for storing and pumping fluids in microfluidic devices fabricated in poly(dimethylsiloxane) (PDMS) using TWIST valves. The method uses valves to isolate microfluidic reservoirs that are filled with solutions Figure 7 of reagents under pressure; the fluid is released, and the flow rate controlled, by opening one of the valves. Figure 9 shows a microfluidic pump fabricated using this approach. http://gmwgroup.harvard.edu/research_microfluidics.html 11/6/2008 EFTA_R1_01521567 EFTA02444652 Whitesides Group - Research Page 3 of 7 References 1. Jeon, N. L. et al. "Generation of Solution and Surface Gradients Using Microfluidic Systems", Langmuir, 2000, 16, 8311-8316. 2. Wu, H. et al. "Fabrication of Topologically Complex Three-Dimensional Microstructures: Metallic Microknots" J. Am. Chem. Soc., 2001, 122, 12691-12699. Figure 8 3. Stroock, A. D. et al. "Chaotic Mixer for Microchannels" Science, 2002, 295, 647-654. 4. Xu, S. et al "Generation of Monodisperse Particles by Using Microfluidics: Control over Size, Shape, and Composition" Angewandte Chemie 44 (5), 2005, 724-728. 5. Weibel, D. B. et al. "Torque-Actuated Valves for Microfluidics" Analytical Chemistry 77(15); 4726-4733, 2005. Figure 9 http://gmwgroup.harvard.edu/reseatth_microfluidics.html 11/6/2008 EFTA_R1_01521588 EFTA02444653 Whitesides Group - Research Page I of 7 The Whitesides Research Group Research Fluidic Optics c1— I 'me WO* Photonics deals with photons as a medium for transmitting information. Typically, photonic circuits either rely on 004 Ckiya passive devices with pre-designed optical functions, or use 0llg•ctib. active components where application of external fields changes the optical properties of the materials (e.g. in Can null Wei electro-optical devices). Our projects in fluidic optics explore alternatives to application of external fields - in these projects we demonstrate the generation and reconfiguration of photonic devices in real time by manipulating flowing liquids. Figure 1 Fluid Optical Waveguides We take advantage of laminar flow in microscopic channels (i.e. microfluidic systems) and of diffusion. In the simplest , demonstration, we sandwich a fluid of higher index of refraction between two streams of liquid with lower index of refraction (Figuire 1). In microchannels, the liquids 11. flowing through the channel will not mix except by molecular diffusion; thus, the flow is laminar and the two liquids flowing side-by-side form an optically smooth Figure 2 interface [1,2]. This system acts as a waveguide (we call it a "liquid-liquid" or L2 waveguide). Fluid optical waveguides are fabricated easily and rapidly in organic polymers using the convenient techniques for rapid prototyping developed in our group. The L2 waveguides are dynamic their structure and function depend on a continuous flow of the core and cladding liquids. They can be reconfigured, renewed (if damaged), and continuously adapted in ways that are not possible with solid-state waveguides. Manipulation of the rate of flow and the composition of the liquids (thus the optical properties) tunes the characteristics of these optical systems in real time. Figure 3 Currently, we are studying the design and operation of fluid analogs of several common optical elements: single- and multi-mode waveguides, optical switches, and evanescent couplers [3]. http://gmwgroup.harvard.edu/research_fluidoptics.html 11/6/2008 EFTA_R1_01521589 EFTA02444654 Whitesides Group - Research Page 2 of 7 Generation of Light in Microchannels We have also demonstrated that fluid waveguides can generate light in microchannels, thus simplifying the coupling of light from external sources to these fluidic " • t devices [4]. When laminar streams of fluorescent organic dyes are separated by a low index fluid and illuminated by 620 660 as MO an incandescent light source (Figure 2), they each produce fluorescence of specific color that can be collected and Figure 4 propagated by a fluid waveguide. One can tune the wavelength (color), position, shape and intensity of these microfluidic light sources by making adjustments of the rate of flow or composition of individual streams. Such simple fluidic light sources could be important, for example, for microanalysis "on-chip" in integrated biophotonic microsystems. Microfluidic Dye Laser We used microfluidic technology to design a miniaturized waveguide dye laser, in which the laser cavity contained a liquid core-liquid cladding waveguide (Figure 3). The key feature of the laser is a long optical path length along the waveguide axis that allows us to achieve high gain in one pass and thus lower the threshold for lasing. By adding thin gold coatings on the surfaces of the T-junctions, we built the laser mirrors into flouresent L2 waveguide light source. Rhodamine 640 perchlorate dissolved in methanol served as the core stream, and pure methanol worked as the cladding stream. Optical pumping of the microlaser with a 532-nm frequency-doubled Nd:YAG laser at 50 Hz results in the bandwidth decrease by an order of magnitude at laser threshold (Figure 4). The fluid waveguide laser is readily tunable by continuously varying the composition of the mixed solvent (methanol-dimethylsulfoxide) while using the same concentration of the dye. The ability to easily change wavelength is critical for applications in spectroscopy and for various types of optical detection requiring different wavelengths. Select Publications I. Stroock, A. D.; Dertinger, S. K. W.; Ajdari, A.; Mezic, I.; Stone, H. A.; Whitesides, G. M. Science 2002, 295, 647- 651. 2. Ma, H.; Jen, A. K. Y.; Dalton, L. R. Adv. Mater. 2002, http://gmwgroup.harvard.edu/research_fluidoptics.html 11/6/2008 EFTA_R1_01521570 EFTA02444655 Whitesides Group - Research Page 3 of 7 14, 1339-1365. 3. Wolfe, D. B.; Conroy, R. S.; Garstecki, P.; Mayers, 13. T.; Fischbach, M. A.; Paul, K. E.; Prentiss, M.; Whitesides, G. M. Proc. Nat. Acad. Sci. USA 2004, 101, 12434-12438. 4. Vezenov, D. V.; Mayen, B. T.; Wolfe, D. B.; Whitesides, G. M. Appl. Phys. Lett. 2005, 86, 041104. http://gmwgroup.harvard.edukesearch_fluidoptics.html 11/6/2008 EFTA_R1_01521571 EFTA02444656 Whitesides Group - Research Page I of 8 The Whitesides Research Group Research Simple Nanotechnology "Nanofabrication" is the process of making functional structures with arbitrary patterns having minimum dimensions currently defined (more-or-less arbitrarily) to be —100 nm. Microelectronic devices and information technologies have improved, and will continue to improve, as a result of large-scale, commercial implementation of nanofabrication. The motivation for these improvements is to increase the density of components, to lower their cost, and to increase their performance per device, and per Figure 1 integrated circuit. Methods used to generate nanoscale structures and nanostructured materials are commonly characterized as "top-down" and "bottom-up". The conventional top-down techniques include photolithography and scanning beam (or maskless) lithography (e.g., electron beam and focused ion beam lithography). The limitations of these conventional approaches when applied to innovative problems - high capital and operating costs, the difficulty in accessing the facilities necessary to use them, and their restricted applicability to many important classes of problems - motivate our exploration and development of new, or "unconventional" nanofabrication techniques. Unconventional techniques have the potential to be the Figure 2 ultimate, low-cost method for certain types of nanomanufacturing; approaches based on reel-to-reel ~W our processing are particularly attractive for low-cost processes. Unconventional approaches are also operationally much POMS simpler to use than are conventional techniques, and thus Sbs% help to open nanoscience and nanotechnology to exploration by a wide range of disciplines, especially those historically only weakly connected to electrical engineering and applied SAA% 1Rentovesuire physics. Nanofabrication by Molding Figure 3 The Whitesides group has developed four unique methods for fabricating nanostructures by molding (Figures 1, 2): (1) Replica Molding (RM) consists of three steps: i) creating a topographically patterned master (usually by conventional techniques; see, for example, ii) transferring the pattern of http://gmwgroup.harvard.edu/research_simpnanotech.html 11/6/2008 EFTA_R1_01521572 EFTA02444657 Whitesides Group - Research Page 2 of 8 this master into PDMS by replica molding; and iii) fabricating a replica of the original master by solidifying a liquid precursor against the PDMS mold. (2) Solvent- Assisted Micromolding (SAMIM) uses an elastomeric mold and an appropriate solvent to emboss polymer films. (3) Micromolding In Capillaries (MIMIC) uses capillarity to fill a series of channels in a topographically patterned PDMS • stamp with a fluid, low-viscosity polymer or ceramic precursor. (4) Microtransfer Molding (µTM), prepolymer fills the recessed regions of the mold, and excess Figure 4 prepolymer is removed from the top surface using a flat edge. After placing the mold in contact with a rigid substrate, the prepolymer is cured by appropriate means. St0ftb Dig." er.tj Nanofabrication by Stamping Su04//ate phookslit We have developed two methods for patterning molecules -SO • 2/0 non on surfaces with high resolution (Figure 3). In microcontact printing (µCP), molecules are transfered from a patterned Substrate PDMS stamp to a substrate by the formation of covalent bonds. In electrical microcontact printing (e-µCP), a flexible Figure 5 electrode is used to pattern a thin film of electret-based material (i.e., that accepts and maintains an electrostatic potential), probably by injecting and trapping charges. Edge Lithography We are exploring several methods for creating nanostructures from using the topographical changes in the edges of patterns. One approach is to pattern nanostructures by selective removal or deposition of material at the edges of lithographically-defined topographic features, such as Figure 6 SAMs (Figure 4). A second approach (Controlled Undercutting), patterns arrays of nanostructured trenches can be fabricated by the controlled undercutting of topographic features using isotropic wet etching, followed by deposition of a thin film (Figure 5). A third approach is Phase-Shifting Photolithography (Figure 6). In this technique, the vertical edges of a transparent, topographically patterned substrate can induce changes in the phase of incident, collimated light to create narrow regions of constructive and destructive interference. Phase- Figure 7 shifting photolithography uses this phenomenon to project "dark or "bright" spots of incident light onto the surface of a photoresist. http://gmwgroup.harvard.edu/research_simpnanotech.html 11/6/2008 EFTA_R1_01521573 EFTA02444658 Whitesides Group - Research Page 3 of 8 We and others have discovered that exposing the edge of a thin film can lead to the formation of nanostructure (Figure 7). This method of edge lithography takes advantage of the Owas0 Uwe numerous methods that can grow thin films over large areas with a thickness between 1 and 50 nm. Converting these films - which are thin in the vertical direction - into structures that are thin in the lateral direction is an approach to fabricating nanostructures. Figure 8 Approaching Zero Through Crystalline Fracture (Cracking) • • 1.4 am We have demonstrated a convenient method to generate - A steps in a planar, surface with vertical dimension ranging from the microscale to the atomic ( less than 0.5 nm) scale (Figure 8). The process involves introducing a crack halfway into a wafer of single-crystal silicon. These cracks 23nn have the following attributes: i) they are continuous steps of smoothly decreasing height, which run in straight lines along crystal planes; ii) the step edges of the cracks are typically —10 µm in height at edge of the wafer (where they Figure 9 initiate) and decrease to 0 nm at the "tip" of the crack (where they disappear into the atomically smooth surface of the silicon wafer; hence "approaching zero"); and iii) these steps are continuous and linear, thereby making them easy to find and characterize. We demonstrate the use of crystal fracture for metrology in nanosciencc, by probing the limits of polymeric replication with 0.4 nm resolution (Figure 9). Functional, Dispersable, Nanostructures from Templates Figure 10 Metallic half-shells with submicron diameters: We have demonstrated the use of spherical silica colloids on substrate as template on which metallic half-shells are formed. Dissolution of the template releases hollow metallic (Au, Pt, Pd) hemispheres with nanometric-scale dimensions (Figure 10). Metallic rods with submicron diameters: We use the method of Martin to perform sequential electrodeposition of multiple components with a porous template and to generate multi-functional nanostructures. For example, it is possible to generate nanorods with alternating sections of gold and nickel (Figure 1 O. The gold provides a surface that can be Figure II functionalized with thiol chemistry, while the nickel allows the nanorods to be manipulated with an external magnetic field. The rods naturally self-assemble into hexagonal bundles through magnetic interactions. The magnetic forces http://gmwgroup.harvard.edu/research_simpnanotech.html 11/6/2008 EFTA_R1_01521574 EFTA02444659 Whitesides Group - Research Page 4 of 8 polarize the disk-like section within the individual rods, perpendicular to the physical (long) axis of the rods and promote lateral interactions that direct the self-assembly of the rods. Free-standing metallic pyramidal shells: We fabricate metallic shells with a pyramidal structure where the tips have a radius of curvature of —50 nm (Figure 12). The templates are formed by anisotropic etching of Si. The metal shells are formed by electrodeposition. The uniformity of Figure 12 the templates fabricated by photolithography or soft lithography ensures the uniformity in shape and size of the pyramidal shells. Select Publications 1. Xia, Y. and Whitesides, G. M. Angew. Chem. 1998, 37, 550. 2. Xia, Y. et al. Chem. Rev. 1999, 99, 1823. 3. Gates, B. D. et al. Annu. Rev. Mater. Res. 2004, 34, 339. 4. Gates, B. D. et al. Chem. Rev. 2005, in press 5. Kim, E., Xia, Y. and Whitcsides, G. M. Nature 1995, 376, 581. 6. Zhao, X., Xia, Y. and Whitesides, G. M. Adv. Mat. 1996, 8, 837. 7. Xia, Y. et al. Science 1996, 273, 347. 8. Odom, T. W. et al. Langmuir 2002, 18, 5314. 9. Gates, B. D. and Whitesides, G. M. SACS 2003, 125, 14986. 10. Xu, Q. et al. JACS, 2005, 127, 854-855. 11. Kumar, A., Biebuyck, H. A. and Whitesides, G. M. Langmuir 1994, 10, 1498. 12. Love, J. C. et al. JACS 2002, 124, 1576. 13. Jacobs, H. O. and Whitesides, G. M. Science 2001, 291, 1763. 14. Aizenberg, J., Black, A. J. and Whitesides, G. M. Nature 1999, 398, 495. 15. Odom, T. W. et al. JACS 2002, 124, 12112. 16. Love, J. C., Paul, K. E. and Whitesides, G. M. Adv. Mater. 2001, 13, 604. 17. Xu, Q., Gates, B. and Whitesides, G. M. SACS 2004, 126, 1332. 18. Gates, B. D. et al. Angew. Chem. Int. Ed. 2004, 43, 2780. 19. Xu, Q. et al. JACS, 2005, 127, 854-855. 20. Love, J. C. et al. Nano.Lett. 2002, 2, 891. 21. Love, J. C. et al. JACS. 2003, 125, 12696. 22. Qiaobing, X. et al. Nano.Lett. 2004, 4, 2509. http://gmwgroup.harvard.edu/research_simpnanotech.html 11/6/2008 EFTA_R1_01521575 EFTA02444660 Whitesides Group - Research Page I of 7 The Whitesides Research Group Research Science for Developing Economies An important problem is to use first-world science to benefit the welfare of people in developing economies. The Whitesides group is using its competencies in materials science, engineering and biology to attack this type of global problem, with a focus on health diagnostics and local energy production. (Other problems include nutrition, sanitation, information technology, education, ecosystem management, and wealth creation.) Figure I Our approach - what we call "simple solutions" - relies on a re-thinking to basic issues of design assumptions, from the ground up, to fit the technology to the socioeconomic constraints present in the developing world. Simple solutions are inexpensive to produce, easy to maintain or replace, simple to use, adaptable to local conditions, scalable for mass consumptions, and easily stored and transported. To the greatest degree possible, they are independent of first-world infrastructure (such as electricity and trained personnel). Health Diagnostics Figure 2 A top priority for improving health in developing countries is technology for simple, affordable diagnosis of infectious diseases. We have developed new approaches that provide low-cost, simple, and reliable solutions for (1) signal amplification and detection in microfluidic devices, (2) reagent handling in microfluidics, (3) fabrication of microfluidic systems, and (4) valving. The work demonstrates the potential of simplifying high-performing devices (such as lab-on-a-chip devices) for use as diagnostic tools in developing economies. Figure 3 POCKET Immunoassay: The POCKET immunoassay "POCKET" is short for portable and cost-effective) is an integrated approach to a miniaturized immunoassay. It is inexpensive and operable with minimal equipment and technical skills, and shows an analytical performance approaching that of enzyme-linked immunosorbent assays http://gmwgroup.harvard.edu/research_devecon.html 11/6/2008 EFTA_R1_01521576 EFTA02444661 Whitesides Group - Research Page 2 of 7 (ELISA). The immunoassay (Figure 1) is performed in an inexpensive, miniaturized platform (made by soft lithography), in which the amplification chemistry is compatible with microfluidics and simple optics. The immunoassay functions with a portable and reusable detector was built from components costing less than S45 US and consists of an InGaAIP red semiconductor laser diode (654 nm) as the light source and an optical integrated Figure 4 circuit as the photodetector (Figure 2). The detector is powered using a single 9V battery and can be used outdoors 1.10 1100 in daylight without changes in background signal. Instead of dilution dilution enzyme-conjugated secondary antibodies in conventional Is ELISA, the system uses antibodies conjugated to 10 nm serum gold colloids; amplification of detection events is I accomplished by electroless deposition of a silver film, Ilt control whose opacity is a function of the concentration of the t_ serum analyte (Figure 3). In sensitivity, limit of detection, and reproducibility, the POCKET immunoassay performs I men comparably to conventional ELISA, and within a factor of 10 of the most sensitive ELISA format - chemiluminescence Figure 5 (Figure 4). The POCKET immunoassay can also reliably distinguish the sera of HIV- I -infected patients from those of noninfected patients (Figure 5). Reagent-Loaded Cartridges: Current techniques for automating fluid delivery in microfluidic devices, which include valves and electroosmosis, require sophisticated microfabrication of the chip, bulky instrumentation, or both. Reagent-loaded cartridges are a simple and reliable technique for storing and delivering a sequence of reagents to a microfluidic device (Figure 6). The technique is low- cost, requires minimal user intervention, and can be performed in resource-poor settings (e.g., outside of a Figure 6 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 (Figure 7). The air spacers prevent the reagents from mixing with each other during cartridge preparation, storage, and usage. As an example, we used this technology to complete an immunoassay with low-nanomolar sensitivity in a microchannel in 2 min; we demonstrated the diagnosis of HIV in 13 min. Figure 7 Novel Energy Concepts Coal is a hugely abundant fuel source. We are exploring approaches to fuel cells in which powdered coal is the fuel. http://gmwgroup.harvard.edu/research_devecon.html 11/6/2008 EFTA_R1_01521577 EFTA02444662 Whitesides Group - Research Page 3 of 7 We have developed a prototype coal fuel cell using a solution of sub-bituminous coal (SBC) partially oxidized by Fe-III (Figure 8). The rate of oxidation depended on the concentration of the kon and the surface area of the coal. At NO; 100 deg C, the maximum current density in the cell was 5 ~hode A/L and the power density was 0.6 W/L. The cell operated Melon Mo without loss of performance for 1000 hours. Select Publications Figure 8 1. Sia, S.K. et al. "An Integrated Approach to Portable and Low-Cost Immunoassay for Resource-Poor Settings." Angew. Chem. Int. Ed. 43, 498-502 (2004). 2. Linder, V., Sia, S.K. and Whitesides, G.M. "Reagent- Loaded Cartridges for Valveless and Automated Fluid Delivery in Microfluidic Dcvices." Anal. Chem. 77, 64-71 (2005). 3. Weibel, D. B. et al "Modeling the Anodic Half-Cell of a Low-Temperature Coal Fuel Cell" Angew. Chem. 44 (35), 2005, 5682-5686. http://gmwgroup.harvard.edu/research_devecon.html 11/6/2008 EFTA_R1_01521578 EFTA02444663 Whitesides Group - Research Paue I of 7 The Whitesides Research Group SINEW Research Complexity and Emergence We are exploring complex and emergent phenomena in several dynamically self-assembling systems. Systems that we have studied include disks spinning at liquid/liquid and liquid/air interfaces, metal beads rolling on polymer ta-in. 00 surfaces, and components moving autonomously on the surface of a hydrogen peroxide solution using bubble-based propulsion. Our recent work in this area focuses on systems in which bubbles and droplets in microfluidic networks are the primary components. Figure I Periodic and Chaotic Formation of Bubbles We are exploring the formation of bubbles in a microfluidic flow-focusing device (Figure I) in which the rate of flow of liquid and the pressure of gas are externally controllable. 11111111111111141111 Over much of the flow rate/pressure phase space, the system 11111111111111111111 produces monodisperse bubbles. We have shown that these bubbles can be used to generate flowing lattices and dynamically assembled foams (Figure 2). As one of the s•ke•kv•kil•k V i V• parameters is varied, however, the sizes of the bubbles e• so••• • GNI lealfafrallIafrafti produced become bi-disperse (Figure 3). Further variation of the parameter leads to periodic production of bubbles of four different sizes. The flow-focusing device can also be Figure 2 tuned to produce bubbles with a random size distribution. The system shows similar behavior to a dripping faucet, which also displays period-doubling bifurcations. Stable, Periodic Behavior in a Bubble-Making System We have extended the flow-focusing device to include five inlets for liquid on either side of the gaseous thread. In a simple flow-focusing device, the gaseous thread advances into the orifice region where it is squeezed closed by the buildup of pressure in the liquid around it. In the five-inlet system, as the gaseous thread advances through the orifice Figure 3 region, it blocks the orifices sequentially, thereby increasing the rate of flow of liquid through the unblocked orifices. The advancing gaseous thread thus creates a mechanism of http://gmwgroup.harvard.edukesearch_complexity.html 11/6/2008 EFTA_R1_01521579 EFTA02444664 Whitesides Group - Research Page 2 of 7 feedback in the system. Bubbles are squeezed off by the downstream orifices as the thread is slowly squeezed at the most upstream orifice, leading to the production of bursts of bubbles (Movie 4). By varying the pressure of gas in the system, for a constant rate of flow of liquid, we can tune the number of bubbles produced by the device in each burst from one up to 40 and back down to -10. We observe highly stable periodic behavior over a range of pressures in which 29 bubbles are produced per period (Figure 5). Movie 4 Solving Mazes Using Bubbles in Microchannels Previously, we have shown that an advancing front of ink in a microfluidic network can elucidate the paths through the network. We are extending this research to incorporate bubbles that move in a continuous flow into the microchannels. The use of bubbles increases the potential utility of these systems as models for complicated networks, such as traffic patterns in a busy city. Select Publications: Figure 5 1. Grzybowski, B. A., Stone, H. A. and Whitesides, G. M. Dynamics of self assembly of magnetized disks rotating at the liquid-air interface. Proceedings of the National Academy of Sciences of the United States of America 99, 4147-4151 (2002). 2. Garstecki, P., Gitlin, I., DiLuzio, W., Whitesides, G. M., Kumacheva E. and Stone, H. A. Formation of monodisperse bubbles in a microfluidic flow-focusing device. Applied Physics Letters 85, 2649-2651 (2004). 3. Wiles, J. A., Grzybowski, B. A., Winkleman, A. and Whitesides, G. M. A tool for studying contact electrification in systems comprising metals and insulating polymers. Analytical Chemistry 75, 4859-4867 (2003). 4. Fuerstman, M. J., Deschatelets, P., Kane, R., Schwartz, A., Kenis, P. J. A., Deutch, J. M. and Whitesides, G. M. Solving mazes using microfluidic networks. Langmuir 19, 4714-4722 (2003). 5. Grzybowski, B. A., Wiles, J. A., and Whitesides, G. M. Dynamic self assembly of rings of charged metallic spheres. Physical Review Letters 90, (2003). 6. Grzybowski, B. A. and Whitesides, G. M. Directed http://gmwgroup.harvard.edukesearch_complexity.hunl 11/6/2008 EFTA_R1_01521580 EFTA02444665 Whitesides Group - Research Page 3 of 7 dynamic self-assembly of objects rotating on two parallel fluid interfaces. Journal of Chemical Physics 116, 8571- 8577 (2002). 7. Grzybowski, B. A. and Whitesides, G. M. Dynamic aggregation of chiral spinners. Science 296, 718-721 (2002). http://gmwgroup.harvard.edukesearch_complexity.html 11/6/2008 EFTA_R1_01521581 EFTA02444666 Whitesides Group - Research Page I of 7 The Whitesides Research Group OMNI'S Research Magnetics The Whitesides group is pursuing several projects involving magnetism. In general we use magnetism as a handle for physical manipulation of objects that are too small to be easily manipulated directly (e.g. with tweezers or micromanipulators). Much of this work is in collaboration with Professors Donald Ingber (HMS) and Mara Prentiss (Physics). Figure I Multifunctional Micro- and Nano-Rods This project involves the fabrication of multifunctional anisotropic structures through electrodeposition inside porous templates. For example, we have demonstrated the synthesis of metallic rods with submicron diameters that contain disk-like ferromagnetic sections (Figure 1) [1]. The metallic sections of these nanorods can be easily functionalized using thiol chemistry, while the magnetic portions provide a handle for manipulation with external magnetic fields. These rods also self-assemble into highly stable, hexagonally close-packed arrays (Figure 2). This configuration minimizes the energy of the bundle and does Figure 2 not generate a net dipole for the structure. This work provides a simple demonstration that magnetic interactions between ferromagnetic objects can direct and stabilize the formation of ordered, 3D structures by self-assembly. •••••••• Magnetic Spheres We are currently developing methodologies for generating was .••• •••.• • homogeneous ferromagnetic nanoparticles coated with a uniform thin layer of gold. Similar to the multifunctional rods, these core-shell structures could be easily modified with functional bio-molecules (e.g. proteins, DNAs, etc) and Figure 3 then manipulated with external magnetic fields. We are also exploring the synthesis and use of functionalizable metallic/magnetic spheres in the form of half-shells (Figure 3) [2]. We have demonstrated that it is possible to use spherical colloids (e.g. silica or polystyrene) as templates http://gmwgroup.harvard.edukesearch_magnetics.html 11/6/2008 EFTA_R1_01521582 EFTA02444667 Whitesides Group - Research Page 2 of 7 for vapor-phase metal deposition. In this case, we deposit colloids in a monolayer on a flat substrate and evaporate first a magnetic layer, then a metallic layer. The colloids can be either resuspended in solution to give half-coated spheres, or dissolved to give half-shells. Magnetic Separations We are actively examining the potential for using functional magnetic micro- and nano-structures in microfluidics [3,4]. One potential use for such structures is in microfluidic separations. We can use functional magnetic particles to bind to certain components of a mixture selectively. We can flow this mixture down a microfluidc channel with multiple outlets. Application of a magnetic field gradient across the channel can be used to direct the magnetic labeled components in the mixture into a specific outlet. The factors that determine the efficiency of this system include: strength of the magnetic field, magnetic susceptibility of the particles, viscosity of the liquid, and flow rate. Magnetic Traps This project involves the fabrication of three-dimensional magnetic traps for diamagnetic objects in an aqueous solution of paramagnetic ions [5]. We have demonstrated trapping of polystyrene spheres, and of various types of living cells: mouse fibroblast (NIH-313), yeast (Saccharomyces cerevisae), and algae (Chlamydomonas reinhardtii). The trapped particle and location of the magnetic trap can be translated in three dimensions by independent manipulation of the magnets that contribute to the overall magnetic field. Magnetic Tweezers We have