Whitesides Group - Research Page 1 of 7

Whitesides Group - Research Page 1 of 7 The Whitesides Research Group 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 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 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 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 SIMMS Figure 1 Figure 2 Figure 3 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. Electrokinetic Flow in Microfluidic Channels We are exploring electrokinetically-driven microfluidic systems for separation of complex biological samples. Our 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. TWIST Valves We have developed a new approach for controlling the flow of fluids in microfluidic channels. TWIST valves consist of small machine screws (500 um diameter) 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 (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 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 (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 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. -stasktA V2 cycle Itaal Figure 4 -• - • - •-• •-• ••• O'N 3•N L. JINN 7C-47-reckti Figure 5 Movie 6 Int Figure 7 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. 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 8 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 Photonics deals with photons as a medium for transmitting information. Typically, photonic circuits either rely on passive devices with pre-designed optical functions, or use active components where application of external fields changes the optical properties of the materials (e.g. in 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. 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 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 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. 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]. 11.c1— I 'me WO* 004 Ckiya 0llg•ctib. Can null Wei Figure 1 , Figure 2 Figure 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 devices [4]. When laminar streams of fluorescent organic dyes are separated by a low index fluid and illuminated by an incandescent light source (Figure 2), they each produce fluorescence of specific color that can be collected and 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, " • t 620 660 as MO Figure 4 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 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 ultimate, low-cost method for certain types of nanomanufacturing; approaches based on reel-to-reel processing are particularly attractive for low-cost processes. Unconventional approaches are also operationally much simpler to use than are conventional techniques, and thus 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 physics. Nanofabrication by Molding 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 Figure 1 Figure 2 ~W our POMS Sbs% SAA% 1 Rentovesuire Figure 3 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 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. Nanofabrication by Stamping We have developed two methods for patterning molecules on surfaces with high resolution (Figure 3). In microcontact printing (µCP), molecules are transfered from a patterned PDMS stamp to a substrate by the formation of covalent bonds. In electrical microcontact printing (e-µCP), a flexible 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 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- shifting photolithography uses this phenomenon to project "dark or "bright" spots of incident light onto the surface of a photoresist. • Figure 4 -SO • 2/0 non St0ftb Dig." er.tj Su04//ate Substrate phookslit Figure 5 Figure 6 Figure 7 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 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. Approaching Zero Through Crystalline Fracture (Cracking) We have demonstrated a convenient method to generate 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 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 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 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 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 Owas0 Uwe Figure 8 • • 1.4 am - A 23nn Figure 9 Figure 10 Figure II 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 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. Figure 12 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.) 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 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. 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 Figure I Figure 2 Figure 3 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 circuit as the photodetector (Figure 2). The detector is powered using a single 9V battery and can be used outdoors in daylight without changes in background signal. Instead of enzyme-conjugated secondary antibodies in conventional ELISA, the system uses antibodies conjugated to 10 nm gold colloids; amplification of detection events is accomplished by electroless deposition of a silver film, whose opacity is a function of the concentration of the analyte (Figure 3). In sensitivity, limit of detection, and reproducibility, the POCKET immunoassay performs comparably to conventional ELISA, and within a factor of 10 of the most sensitive ELISA format - chemiluminescence (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 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. Novel Energy Concepts Coal is a hugely abundant fuel source. We are exploring approaches to fuel cells in which powdered coal is the fuel. Figure 4 1.10 1100 dilution dilution Is I Ilt t_ I men serum control serum Figure 5 Figure 6 Figure 7 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 100 deg C, the maximum current density in the cell was 5 A/L and the power density was 0.6 W/L. The cell operated without loss of performance for 1000 hours. Select Publications 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. NO; ~hode Melon Mo Figure 8 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 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 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. 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. Over much of the flow rate/pressure phase space, the system 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 parameters is varied, however, the sizes of the bubbles 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 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 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 SINEW ta-in. 00 Figure I 11111111111111141111 11111111111111111111 s•ke•kv•kil•k iVV• e• so••• • GNI lealfafrallIafrafti Figure 2 Figure 3 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). 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: 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 Movie 4 Figure 5 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 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). 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 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 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 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 OMNI'S Figure I Figure 2 •••••••• • • was .•• • . • • • Figure 3 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 recently begun a project to measure the rates of protein-ligand dissociation in a single-molecule format, using magnetic forces. We have been able to extrapolate to the rate constant for dissociation in the absence of an applied force and have obtained values that are in good agreement with rate constants from other techniques for a representative protein-ligand pair. We will extend this technique to protein-ligand complexes that exhibit complicated energy landscapes that cannot be followed adequately using ensemble averaging techniques and other interesting biological systems. http://gmwgroup.harvard.edukesearch_magnetics.html 11/6/2008 EFTA_R1_01521583 EFTA02444668 Whitesides Group - Research Page 3 of 7 Select Publications: 1. Love, J. C. et al. "Three-Dimensional Self-Assembly of Metallic Rods with Sub-Micron Diameters Using Magnetic Interactions". Journal of the American Chemical Society 125, 12696-12697 (2003). 2. Love, J. C. et al. "Fabrication and Wetting Properties of Metallic Half-Shells with Sub-Micron Diameters. Nano Letters 2, 891-894 (2002). 3. Deng, T. Prentiss, M. and Whitesides, G. M. "Fabrication of magnetic microfiltration systems using soft lithography". Applied Physics Letters 80, 461463 (2002). 4. Deng, T. et al. "Manipulation of magnetic microbeads in suspension using micromagnetic systems fabricated with soft lithography." Applied Physics Letters 78, 1775-1777 (2001). 5. Winkleman, A., et al. "A magnetic trap for living cells suspended in a paramagnetic buffer". Applied Physics Letters 85, 2411-2413 (2004). http://gmwgroup.harvard.edukesearch_magnetics.html 11/6/2008 EFTA_R1_01521584 EFTA02444669 Whitesides Group - Research Page I of 6 The Whitesides Research Group Research Electrets Electrets are materials that contain permanent charges or permanently induced dipoles. They have a permanent electric field, just as permanent magnets have a permanent magnetic field. Electrets have been used for decades in audio and video equipment, telephones and microphones, photocopiers, printers, spray painters, and other technologies that depend on charged materials. We are examining the fundamental properties of electrets as materials. We use these materials for self-assembly and to understand the fundamental processes involved with producing (and preventing) charge on materials. Fluid Electrets We are examining the mechanism of charging in pure protic and aprotic solvents. We systematically dope these solvents with various solutes; small changes in the concentration of these solutes affect the charging of the fluid as it flows through a capillary under an applied potential. It is easier to perform such a systematic study using fluids, rather than solids, because fluids can be doped in a readily well- controlled, quantitative manner. Understanding the mechanism of charging fluids is of fundamental importance for understanding electrochemical processes. The motivation for this study originates from an attempt to understand the underlying mechanism for charging in a Kelvin electrostatic generator (Movie 1). In this movie, you can see the generator charge - dyed water droplets fly away from the collection (bottom) electrodes and coat the white backdrop - and discharge - the droplets fall straight into the collection electrodes. Self-Assembly of Microspheres We have shown that glass microspheres self-assemble on a patterned electrode under the influence of an applied electric field (Figure 2). This process occurs for ordered arrays and Movie I . • •:.:4).#41:1°. .r •••• 1.•••••;.: n'attii••• at": ..... 1:::•r"" :::: :::::: matt» • ••••••• :::::: ...assn.& an Figure 2 http://gmwgroup.harvard.edu/research_elecirets.html 11/6/2008 EFTA_R1_01521585 EFTA02444670 Whitesides Group - Research Page 2 of 6 arbitrary patterns, over areas up to —0.7 cm^2, with a defect rate (e.g., missing spheres, or extra spheres) of about 1%. These arrays of microspheres on the surface of the electrode can be transferred into polymeric matrices. This method employs reusable templates to guide components rapidly (less than 5 seconds) into ordered structures that cannot be made by traditional lithographic techniques. Select Publications 1. Wiles, J. A., et al. "A Tool for Studying Contact Electrification in Systems Comprising Metals and Insulating Polymers." Analytical Chemistry 75, 4859-4867 (2003). 2. Grzybowski, B. A., et al. "Electrostatic Self-Assembly of Macroscopic Crystals using Contact Electrification." Nature Materials 2, 241-245 (2003). http://gmwgroup.harvard.edu/research_electrets.html 11/6/2008 EFTA_R1_01521588 EFTA02444671 Whitesides Group - Research Page I of 7 The Whitesides Research Group Research Surface Science Microcontact Printing of Self-Assembled Monolayers We are interested in organic surface science and its applications across science and technology. We have studied the conversion of alkanethiols into self-assembled monolayers (SAMs) on surfaces (Figure I ) and patterned SAMS for microcontact printing. In this technique, a PDMS stamp is constructed using soft-lithography. The stamp is then wetted with an alkanethiol and placed in contact with a gold (or other noble metal) for several seconds. SAMs form on the surface only in the areas that had been in contact with the stamp (Figure 2). Microcontact printing of SAMs has a number of applications. By patterning one SAM with a hydrophobic terminus and then filling in the rest of the area with a SAM with a hydrophilic terminus, it is possible to create hydrophobic (or hydrophilic) patterns on surfaces with micron dimensions (Figures 3,4). Patterning specific areas with cell-friendly (protein terminated) and cell-unfriendly (polyethylene -glycol terminated) SAMs can be used to pattern endothelial cells on surfaces and to even force these cells to take on specific shapes (Figure 5). Electrochemical Desorption of Self-Assembled Monolayers We have also shown that alkanethiol SAMs can be released from surfaces when a small (less than 1 V) potential is applied across the surface; this process is called "electrochemical desorption" (Figure 6). In one application of electrochemical desorption, polyethylene -glycol terminated SAMs are pattered around islands protein- terminated SAMs. Applying the potential releases the polyethylene -glycol SAMs from the surface and allows the cells to spread out from confinement. This technique has allowed us to tune the inertness of surfaces in real time and to design cell motility assays (Movie 7). Figure I — _ I f:-.5:74Imnm:IPEnmt Figure 2 Figure 3 Figure 4 http://gmwgroup.harvard.edu/research_surfacescience.html 11/6/2008 EFTA_R1_01521587 EFTA02444672 Whitesides Group - Research Page 2 of 7 Surface Analytical Techniques We also use a number of surface analytical techniques to characterize the surface coatings of PDMS and glass; such techniques include x-ray photoelectron spectroscopy (XPS), reflectance IR and ellipsometry. Controlling surface properties of these materials is important for biological applications. These properties are particularly important in the field of electrokinetic injections and separation, because they affect adsorption of proteins as well as surface charge, which determines the magnitude of electroosmotic flow (EOF). In turn, measurements of EOF allow us to infer the density of surface charge and its surface uniformity. Figure 8 shows an XPS signal describing the presence of nitrogen from polyacrylamide photopolymerized inside a sealed PDMS channel. Select Publications 1. Laibinis, P. E. et al. "Orthogonal self-assembled monolayers: alkanethiols on gold and alkane carboxylic acids on alumina." Science (1989), 245(4920), 845-7. 2. Abbott, N. L., Folkers, J. P. and Whitesides, G. M. "Manipulation of the wettability of surfaces on the 0.1- to 1- micrometer scale through micromachining and molecular self-assembly." Science (1992), 257(5075), 1380-2. 3. Kumar, A., Biebuyck, H. A. and Whitesides, G. M. "Patterning Self-Assembled Monolayers: Applications in Materials Science." Langmuir (1994), 10(5), 1498-511. 4. Wilbur, J. L. et al. "Microcontact printing of self- assembled monolayers: applications in microfabricaticm " Nanotechnology (1996), 7(4), 452457. 5. Kane, R. S. et al. "Patterning proteins and cells using soft lithography." Biomaterials (1999), 20(23/24), 2363-2376. 6. Jiang, X. et al. "Electrochemical desorption of self- assembled monolayers noninvasively releases patterned cells from geometrical confinements." JACS (2003), 125, 2366-2367. Figure 5 a, a I a a AI 1 al al MI a.). a a AN Figure 6 e S Movie 7 Figure 8 http://gmwgroup.harvard.edu/research_surfacescience.html 11/6/2008 EFTA_R1_01521588 EFTA02444673 Whitesides Group - Research Page I of 7 The Whitesides Research Group Research Self Assembly In any living cell, nanoscale cellular machines spontaneously assemble themselves and drive the processes of life. Improvements in fabrication techniques are pushing the dimensions of electronic components to regimes beyond the reach of direct manipulation by human or machine. The functional self-assembly sub-group at the Whitesides Lab seeks to design self-assembling systems at a variety of scales, and to use these systems to form working devices that would be difficult (or practically impossible) to build with any other technique. Self-assembly involves spontaneous organization of interacting components into an ordered aggregate or aggregates without direct human or mechanical interference. In the natural world, self-assembly occurs over a wide range of size-scales to create structures that display new properties not present in the original components. Self-assembly occurs both in systems at equilibrium - such as the crystallization of proteins or colloids - and in systems far from equilibrium - such as cellular replication of DNA. This work seeks to exploit the power of self-assembly to order small components into functional, three-dimensional structures in a parallel process. Driving Forces We have demonstrated the self-assembly of functional electronic devices with components as small as 100 microns on a side. Figure I describes a self-assembled GaAs display. Figure 2 describes 1560 silicon blocks self-assembled onto a flexible substrtate. To provide the interactions between components, our past work relied on the capillary interaction between menisci, drops of hydrophobic liquid, or pads of molten metal; more recent work has used electrostatic or magnetic interactions. Perfecting Self-Assembly Figure I • WO Nall •WIONtitlIC 3 Arum= on &VW a • it-u • st Wirt wend runt It AtA twat SPE MOM X 0-a s s ii Figure 2 Figure 3 http://gmwgroup.harvard.edu/research_selfassembly.htrn1 11/6/2008 EFTA_R1_01521589 EFTA02444674 Whitesides Group - Research Page 2 of 7 Two main problems complicate the design of self- assembling systems: maximization ofyield and fabrication of components. To improve the yield of self-assembly, we have demonstrated templating of the self-assembly process. Templating can include constraining the aggregation in a container of a particular shape, and tethering the components together on a flexible ribbon or polymer sheet. The strategy of confining components to a flat sheet is particularly interesting to us, because we can use photolithography and other established methods to fabrication components in two-dimensions, and then allow the sheet to fold spontaneously by self-assembly into a functional three-dimensional shape. Once we have techniques to pattern components for function and self- assembly in parallel, it will be easy to decrease the size of the components even further. To date, most functional assemblies have been composed of either very simple components (e.g., silicon blocks) or relatively large ones (mm-scale). A "synthetic" approach to the fabrication of individual components will lead to greater understanding of the self-assembly process, and to smaller, better devices. Projects Self-healing materials: Wires and bonds made from low- melting conductive alloys can spontaneously heal upon heating. It is possible to fix devices based on self-healing materials from the outside, with no disassembly required. Figure 3 describes a self-healing "spine"; Figure 4 describes a composite of a flexible polymer and molten metal, tat spontaneously folds into a helix. We have also used these techniques to describe a functional 3D sphere folded from a sheet by magnetic forces (Figure 5). Folding tapes and sheets: Capillary forces between patterns of molten metal (or other liquid with high surface free energy) lead to ordered folded structures. As with proteins, the primary structure of the precursor - that is, the sequence and spacing of "monomers" with various sizes, hydrophobicity, or other forms of patterning - determines the structure of the final product. Unlike the synthesis of proteins, we are free to begin with either linear chains or flat sheets of unfolded components. Passive electronic components: Self-assembly offers a potential method for reducing the footprint of passive components (capacitors, inductors, and resistors) on microchips. In experiments we have shown that the same components can assemble into different devices when these components are placed in different containers. Figure 4 Figure 5 Figure 6 Figure 7 http://gmwgroup.harvard.edu/research_selfassembly.htrn1 11/6/2008 EFTA_R1_01521590 EFTA02444675 Whitesides Group - Research Page 3 of 7 Plasticity and redundancy: In these experiments, we show that designing components that self-assemble to different products under different macroscopic conditions, or components with redundant elements, will lead to reconfigurable devices. Specifically, Shape- complementarity can improve the yield of self-assembly (Figure 6) Three-dimensional recognition: Most photolithographic methods are optimized for the fabrication of two- dimensional patterns. Biological recognition depends on both chemical interactions and shape recognition. This work seeks to improve yield of self-assembly through improved design of high surface energy recognition patterns, and improved fabrication of three-dimensional components for shape-complementarity (Figure 7, Figure 8). Select Publications Boncheva, M. et al. "Magnetic Self-Assembly of Three- Dimensional Surfaces from Planar Sheets." PNAS 102, 3924-3929 (2005). Boncheva, M., Bruzewicz, D. A. & Whitesides, G. M. "Millimeter -Scale Self-Assembly and Its Applications." Pure Appl. Chem. 75, 621-630 (2003). Boncheva, M., Bruzewicz, D. A. & Whitesides, G. M. "Formation of Chiral, Three-Dimensional Aggregates by Self-Assembly of Helical Components." Langmuir 19, 6066-6071 (2003). Boncheva, M. et al. "Plasticity in Self-Assembly: Templating Generates Functionally Different Circuits from a Single Precursor." Angew. Chem. Int. Ed. 42, 2644-2647 (2003). Boncheva, M. & Whitesides, G. M. "Self-healing systems having a design stimulated by the vertebrate spine." Angew. Chem. Int. Ed. 42, 2644-2751 (2003). Gracias, D. H. et al. "Forming Electrical Networks in Three Dimensions by Self-Assembly." Science 289, 1170-1172 (2000). Jacobs, H. O. et al. "Fabrication of a Functional Cylindrical Dis