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Showing papers by "George M. Whitesides published in 2000"


Journal ArticleDOI
TL;DR: Fabrication of microfluidic devices in poly(dimethylsiloxane) (PDMS) by soft lithography provides faster, less expensive routes to devices that handle aqueous solutions.
Abstract: Microfluidic devices are finding increasing application as analytical systems, biomedical devices, tools for chemistry and biochemistry, and systems for fundamental research. Conventional methods of fabricating microfluidic devices have centered on etching in glass and silicon. Fabrication of microfluidic devices in poly(dimethylsiloxane) (PDMS) by soft lithography provides faster, less expensive routes than these conventional methods to devices that handle aqueous solutions. These soft-lithographic methods are based on rapid prototyping and replica molding and are more accessible to chemists and biologists working under benchtop conditions than are the microelectronics-derived methods because, in soft lithography, devices do not need to be fabricated in a cleanroom. This paper describes devices fabricated in PDMS for separations, patterning of biological and nonbiological material, and components for integrated systems.

3,344 citations


Journal ArticleDOI
07 Oct 2000-Langmuir
TL;DR: In this paper, the authors describe a simple, versatile method of generating gradients in composition in solution or on surfaces using microfluidic systems based on controlled diffusive mixing of species in solutions that are flowing laminarly, at low Reynolds number, inside a network of microchannels.
Abstract: This paper describes a simple, versatile method of generating gradients in composition in solution or on surfaces using microfluidic systems. This method is based on controlled diffusive mixing of species in solutions that are flowing laminarly, at low Reynolds number, inside a network of microchannels. We demonstrate the use of this procedure to generate (1) gradients in the compositions of solutions, measured directly by colorimetric assays and (2) gradients in topography of the surfaces produced by generating concentration gradients of etching reagents, and then using these gradients to etch profiles into the substrate. The lateral dimensions of the gradients examined here, which went from 350 to 900 μm, are determined by the width of the microchannels. Gradients of different size, resolution, and shape have been generated using this method. The shape of the gradients can be changed continuously (dynamic gradients) by varying the relative flow velocities of the input streams of fluids. The method is ex...

961 citations


Journal ArticleDOI
TL;DR: This method can generate topologically complex microfluidic systems and can fabricate a membrane containing a channel that crosses over and under itself, but does not intersect itself and, therefore, can be fabricated in the form of any knot.
Abstract: This paper describes a procedure for making topologically complex three-dimensional microfluidic channel systems in poly(dimethylsiloxane) (PDMS). This procedure is called the “membrane sandwich” method to suggest the structure of the final system: a thin membrane having channel structures molded on each face (and with connections between the faces) sandwiched between two thicker, flat slabs that provide structural support. Two “masters” are fabricated by rapid prototyping using two-level photolithography and replica molding. They are aligned face to face, under pressure, with PDMS prepolymer between them. The PDMS is cured thermally. The masters have complementary alignment tracks, so registration is straightforward. The resulting, thin PDMS membrane can be transferred and sealed to another membrane or slab of PDMS by a sequence of steps in which the two masters are removed one at a time; these steps take place without distortion of the features. This method can fabricate a membrane containing a channel...

745 citations


Journal ArticleDOI
TL;DR: Three-dimensional microfluidic systems were fabricated and used to pattern proteins and mammalian cells on a planar substrate to pattern multiple types of proteins and cells in complex, discontinuous structures on a surface.
Abstract: Three-dimensional microfluidic systems were fabricated and used to pattern proteins and mammalian cells on a planar substrate. The three-dimensional topology of the microfluidic network in the stamp makes this technique a versatile one with which to pattern multiple types of proteins and cells in complex, discontinuous structures on a surface. The channel structure, formed by the stamp when it is in contact with the surface of the substrate, limits migration and growth of cells in the channels. With the channel structure in contact with the surface, the cells stop dividing once they form a confluent layer. Removal of the stamp permits the cells to spread and divide.

632 citations


Journal ArticleDOI
TL;DR: In this article, the authors describe an experimentally straightforward procedure for preparing and screening surfaces for their ability to resist the adsorption of proteins from solution, which is referred to as protein resistant surfaces.
Abstract: This contribution describes an experimentally straightforward procedure for preparing and screening surfaces for their ability to resist the adsorption of proteins from solution. For brevity, we call surfaces “protein resistant” when they are resistant to the adsorption of proteins from solution. We have used this procedure to identify several functional groups that had not previously been recognized as protein resistant. This work both identifies a number of functional groups that will be useful in designing resistance to the adsorption of biomolecules into devices used in sensing and in cell biology,1-3 and contributes to an understanding of the mechanism of action of protein resistant surfaces by correlating this property with molecular-scale structure.4-6 We combined self-assembled monolayers (SAMs)7,8 and surface plasmon resonance (SPR) spectroscopy9 into a system that enabled us to screen a number of functional groups rapidly for their ability to resist the adsorption of proteins. The surfaces were prepared by the “anhydride method” (Figure 1).10,11 This reaction generates a “mixed” SAM that comprises an ∼1:1 mixture of -CONRR′ and CO2H/CO2 groups.10,12 (We have not defined the state of the ionization of the CO2H groups in these SAMs.) The ease with which this class of mixed SAMs can be prepared by the anhydride method (relative to the synthesis of the functionalized alkanethiols HS(CH2)nR′ normally used for the preparation of singlecomponent SAMs) makes this route efficient for exploratory and screening work.11,13 We have examined the adsorption of two proteins to these surfaces: fibrinogen, a large (340 kD) blood plasma protein that adsorbs strongly to hydrophobic surfaces, and lysozyme, a small protein (14 kD, pI ) 12) that is positively charged under the conditions of our experiment (phosphate buffered saline, PBS, pH 7.4). Fibrinogen is used as a model for “sticky” serum proteins;11,14,15 lysozyme is often used in model studies of electrostatic adsorption of proteins to surfaces.16,17 Since lysozyme has a substantial net positive charge (Zp ) + 7.5 at pH 7.4, 100 mM KCl),18 it allowed us to examine attractive electrostatic interactions with CO2 groups on the surface. We have prepared more than 50 surfaces, each presenting a different functional group, using the anhydride procedure, and surveyed them for protein resistance.19 Table 1 summarizes selected results from this survey. The amount of protein adsorbed (∆RU ) change in response units) as measured by SPR was determined by subtracting the value of RU prior to the injection of protein from the value of RU measured 10 min after the completion of the protein injection; for clarity, these points are each labeled with a vertical dashed line in Figure 2. The value of ∆RU was used to calculate the percentage of a monolayer (%Monolayer) of that protein using eq 1.11,20 We define “%ML” according to eq 1 strictly to simplify the comparison between surfaces.

576 citations


Journal ArticleDOI
TL;DR: In this article, the authors quantified both experimentally and theoretically the diffusion of low-molecular-weight species across the interface between two aqueous solutions in pressure-driven laminar flow in microchannels at high Peclet numbers, showing that the width of reaction-diffusion zone at the interface adjacent to the wall of the channel and transverse to the direction of flow scales as the one-third power of both the axial distance down the channel (from the point where the two streams join) and the average velocity of the flow, instead
Abstract: This letter quantifies both experimentally and theoretically the diffusion of low-molecular-weight species across the interface between two aqueous solutions in pressure-driven laminar flow in microchannels at high Peclet numbers. Confocal fluorescent microscopy was used to visualize a fluorescent product formed by reaction between chemical species carried separately by the two solutions. At steady state, the width of the reaction–diffusion zone at the interface adjacent to the wall of the channel and transverse to the direction of flow scales as the one-third power of both the axial distance down the channel (from the point where the two streams join) and the average velocity of the flow, instead of the more familiar one-half power scaling which was measured in the middle of the channel. A quantitative description of reaction–diffusion processes near the walls of the channel, such as described in this letter, is required for the rational use of laminar flows for performing spatially resolved surface chemistry and biology inside microchannels and for understanding three-dimensional features of mass transport in shearing flows near surfaces.

558 citations


Journal ArticleDOI
18 Aug 2000-Science
TL;DR: Self-assembly of millimeter-scale polyhedra, with surfaces patterned with solder dots, wires, and light-emitting diodes, generated electrically functional, three-dimensional networks.
Abstract: Self-assembly of millimeter-scale polyhedra, with surfaces patterned with solder dots, wires, and light-emitting diodes, generated electrically functional, three-dimensional networks. The patterns of dots and wires controlled the structure of the networks formed; both parallel and serial connections were generated.

515 citations


Journal ArticleDOI
29 Jun 2000-Nature
TL;DR: This work describes the formation of dynamic patterns of millimetre-sized magnetic disks at a liquid–air interface, subject to a magnetic field produced by a rotating permanent magnet, which should lead to a better understanding of dynamic self-assembly, while providing a test-bed for stability theories of interacting point vortices and vortex patches.
Abstract: Spontaneous pattern formation by self-assembly is of long-standing and continuing interest not only for its aesthetic appeal, but also for its fundamental and technological relevance. So far, the study of self-organization processes has mainly focused on static structures, but dynamic systems--those that develop order only when dissipating energy--are of particular interest for studying complex behaviour. Here we describe the formation of dynamic patterns of millimetre-sized magnetic disks at a liquid-air interface, subject to a magnetic field produced by a rotating permanent magnet. The disks spin around their axes with angular frequency equal to that of the magnet, and are attracted towards its axis of rotation while repelling each other. This repulsive hydrodynamic interaction is due to fluid motion associated with spinning; the interplay between attractive and repulsive interactions leads to the formation of patterns exhibiting various types of ordering, some of which are entirely new. This versatile system should lead to a better understanding of dynamic self-assembly, while providing a test-bed for stability theories of interacting point vortices and vortex patches.

473 citations


Journal ArticleDOI
21 Jan 2000-Science
TL;DR: These highly processible, self-assembling mesostructured host media and claddings may have potential for the fabrication of integrated optical circuits.
Abstract: Mesostructured silica waveguide arrays were fabricated with a combination of acidic sol-gel block copolymer templating chemistry and soft lithography. Waveguiding was enabled by the use of a low-refractive index (1.15) mesoporous silica thin film support. When the mesostructure was doped with the laser dye rhodamine 6G, amplified spontaneous emission was observed with a low pumping threshold of 10 kilowatts per square centimeter, attributed to the mesostructure's ability to prevent aggregation of the dye molecules even at relatively high loadings within the organized high-surface area mesochannels of the waveguides. These highly processible, self-assembling mesostructured host media and claddings may have potential for the fabrication of integrated optical circuits.

461 citations


Journal ArticleDOI
25 Feb 2000-Langmuir
TL;DR: In this paper, the spontaneous formation of aligned buckles in a thin film of gold deposited on the surface of an elastomer [poly(dimethylsiloxane), PDMS] is described.
Abstract: This paper describes the spontaneous formation of patterns of aligned buckles in a thin film of gold deposited on the surface of an elastomer [poly(dimethylsiloxane), PDMS]. The surface of the elastomer is patterned photochemically into areas differing in stiffness and coefficient of thermal expansion. The gold is deposited while the surface of the patterned elastomer is warm (T ∼ 100 °C). On cooling, shrinkage in the elastomer places the gold film under compressive stress. The buckles relieve this compressive stress. The distribution of stresses and buckle patterns is described during the pre- and postbuckling regimes using solutions from calculations describing a model comprising a thin stiff plate resting on a thick elastic foundation.

444 citations


Journal ArticleDOI
30 Aug 2000-Langmuir
TL;DR: This strategy of membrane-based patterning, given the acronym MEMPAT for brevity, offers a more convenient way for patterning cells on surfaces and for studying cell spreading than existing methods.
Abstract: We describe the patterning of proteins and cells onto the surfaces of bacteriological Petri dishes, glass, and poly(dimethylsiloxane) (PDMS) with the use of elastomeric lift-off membranesfree-standing polymer films that have circular or square holes with diameters, sides, and height ≥50 μm. Cells are patterned within the physical constraints provided by the holes of the membranes; these constraints can be released to allow the cells to spread onto the rest of the surface or to remain in the pattern by controlling the properties of the surfaces. Careful control of the properties of the surfaces of the substrates are required to cause the cells to adhere to the substrate and not to the membrane, and to avoid damage to the cells on removing the membrane. This strategy of membrane-based patterninggiven the acronym MEMPAT for brevityoffers a more convenient way for patterning cells on surfaces and for studying cell spreading than existing methods.

Journal ArticleDOI
TL;DR: This Letter reports the measurement of electro-osmotic flows (EOF) in microchannels with surface charge patterned on the 200 microm scale, which agree well with theory in the limit of thin double layers and low surface potential.
Abstract: This Letter reports the measurement of electro-osmotic flows (EOF) in microchannels with surface charge patterned on the 200 mu m scale. We have investigated two classes of patterns: (1) Those in which the surface charge varies along a direction perpendicular to the electric field used to drive the EOF; this type of pattern generates multidirectional flow along the direction of the field. (2) Those in which the surface charge pattern varies parallel to the field; this pattern generates recirculating cellular flew, and thus causes motion both parallel and perpendicular to the external field. Measurements of both of these flours agree well with theory in the Limit of thin double layers and low surface potential.

Journal ArticleDOI
25 Jul 2000-Langmuir
TL;DR: In this paper, a procedure for preparing mixed self-assembled monolayers (mixed SAMs) on gold that resist the nonspecific adsorption of proteins from solution was described.
Abstract: This paper describes a procedure for preparing mixed self-assembled monolayers (mixed SAMs) on gold that resist the nonspecific adsorption of proteins from solution. This method was tested using α-amino derivatives of ω-hydroxy- and ω-methoxy-oligo(ethylene glycols): H2N(CH2CH2O)nCH3 and H2N(CH2CH2O)nH (n = 3, 6). Mixed SAMs were prepared by allowing these amines to react with a SAM presenting interchain carboxylic anhydride groups. The resistance of the resulting surfaces to adsorption of several proteinscarbonic anhydrase (EC 4.2.1.1), ribonuclease A (EC 3.1.27.5), lysozyme (EC 3.2.1.17), and fibrinogenwas examined using surface plasmon resonance (SPR) spectroscopy. These mixed SAMs resist the nonspecific adsorption of proteins approximately as effectively as single-component SAMs prepared using the conventional method involving chemisorption of oligo(ethylene glycol)-terminated alkanethiols on gold. Characterization of the mixed SAM that presents a 1:1 mixture of −OCNH(CH2CH2O)6CH3 and CO2H/CO2- group...

Journal ArticleDOI
TL;DR: This Account summarizes techniques for carrying out microfabrication of structures with dimensions down to 10 microm in microchannels that are 0.02-2 mm wide based on the exploitation of laminar flow at low Reynolds number to control the spatial delivery of reagents.
Abstract: This Account summarizes techniques for carrying out microfabrication of structures with dimensions down to 10 mum in microchannels that are 0.02-2 mm wide. These methods are largely based on the exploitation of laminar flow at low Reynolds number (Re) to control the spatial delivery of reagents. These methods are illustrated by fabrication of fibers, microelectrode arrays, arrays of crystals, and patterns of proteins and cells.

Journal ArticleDOI
TL;DR: In this article, the Seitz Materials Research Laboratory at the University of Illinois at Urbana-Champaign and the Massachusetts Institute of Technology (MIT) have proposed a method for the synthesis of synthetic materials.
Abstract: Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, Department of Chemistry and the Seitz Materials Research Laboratory, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, and Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139

Journal ArticleDOI
TL;DR: A practical method for the fabrication of photomasks, masters, and stamps/molds used in soft lithography that minimizes the need for specialized equipment and time required to go from concept to device is short.
Abstract: This paper describes a practical method for the fabrication of photomasks, masters, and stamps/molds used in soft lithography that minimizes the need for specialized equipment. In this method, CAD files are first printed onto paper using an office printer with resolution of 600 dots/in. Photographic reduction of these printed patterns transfers the images onto 35-mm film or microfiche. These photographic films can be used, after development, as photomasks in 1:1 contact photolithography. With the resulting photoresist masters, it is straightforward to fabricate poly(dimethylsiloxane) (PDMS) stamps/molds for soft lithography. This process can generate microstructures as small as 15 microm; the overall time to go from CAD file to PDMS stamp is 4-24 h. Although access to equipment-spin coater and ultraviolet exposure tool-normally found in the clean room is still required, the cost of the photomask itself is small, and the time required to go from concept to device is short. A comparison between this method and all other methods that generate film-type photomasks has been performed using test patterns of lines, squares, and circles. Three microstructures have also been fabricated to demonstrate the utility of this method in practical applications.

Journal ArticleDOI
TL;DR: An experimental procedure that measures the forces of adhesion resulting from the interaction of uropathogenic Escherichia coli to molecularly well defined models of cellular surfaces and suggests that the combination of optical tweezers and appropriately functionalized SAMs is a uniquely synergistic system with which to study polyvalent adhesion of bacteria to biologically relevant surfaces.
Abstract: Mechanisms of bacterial pathogenesis have become an increasingly important subject as pathogens have become increasingly resistant to current antibiotics. The adhesion of microorganisms to the surface of host tissue is often a first step in pathogenesis and is a plausible target for new antiinfective agents. Examination of bacterial adhesion has been difficult both because it is polyvalent and because bacterial adhesins often recognize more than one type of cell-surface molecule. This paper describes an experimental procedure that measures the forces of adhesion resulting from the interaction of uropathogenic Escherichia coli to molecularly well defined models of cellular surfaces. This procedure uses self-assembled monolayers (SAMs) to model the surface of epithelial cells and optical tweezers to manipulate the bacteria. Optical tweezers orient the bacteria relative to the surface and, thus, limit the number of points of attachment (that is, the valency of attachment). Using this combination, it was possible to quantify the force required to break a single interaction between pilus and mannose groups linked to the SAM. These results demonstrate the deconvolution and characterization of complicated events in microbial adhesion in terms of specific molecular interactions. They also suggest that the combination of optical tweezers and appropriately functionalized SAMs is a uniquely synergistic system with which to study polyvalent adhesion of bacteria to biologically relevant surfaces and with which to screen for inhibitors of this adhesion.

Journal ArticleDOI
TL;DR: The kinetics of dissociation of the aggregate RtV3·R‘tL‘3 is rapid in the presence of monovalent L at concentrations greater than the value of the dissociation constant for the complex of L with V; by contrast, the rate of dissociated biotin·avidin is independent of the concentration of biotin.
Abstract: A trivalent derivative of vancomycin, tris(vancomycin carboxamide), [C6H3-1,3,5-(CONHC6H4-4-CH2NHCOV)3 (RtV3; V = vancomycin)], binds an analogous trivalent derivative of d-Ala-d-Ala, R‘tL‘3, (C6H3-1,3,5-[CONeH(Nα-Ac)-l-Lys-d-Ala-d-Ala]3) in water with a dissociation constant that is approximately 4 × 10-17 M, as estimated by HPLC using a competitive assay against Nα,e-diacetyl-l-Lys-d-Ala-d-Ala (L). This binding is one of the tightest known for low molecular weight organic species. The dissociation of RtV3·R‘tL‘3 in the presence of an excess of L could be followed by HPLC. The kinetics of dissociation are quite different from those of monovalent tight-binding systems such as avidin and biotin. In particular, the rate of dissociation of the aggregate RtV3·R‘tL‘3 is rapid in the presence of monovalent L at concentrations greater than the value of the dissociation constant for the complex of L with V; by contrast, the rate of dissociation of biotin·avidin is independent of the concentration of biotin. Two m...

Journal ArticleDOI
TL;DR: In this paper, the authors describe several soft lithographic techniques that use rubber stamps, molds, and conformable photomasks for micro and nanofabrication, and illustrate how these methods provide low cost routes to patterning for applications in organic electronics and integrated optics.

Journal ArticleDOI
TL;DR: The self-assembly of hexagonal plates at the interface between perfluorodecalin (PFD) and water was described in this paper. But the results were limited to 14 different hexagons that can be made by permuting the number and location of the hydrophobic and hydrophilic faces.
Abstract: This paper describes the self-assembly of hexagonal plates (with 2.7 mm wide sides) at the interface between perfluorodecalin (PFD) and water. All 14 different hexagons that can be made by permuting the number and location of the hydrophobic and hydrophilic faces were examined. The plates attracted one another by lateral capillary forces involving the menisci on the hydrophilic faces. The plates were made of poly(dimethylsiloxane) (PDMS) containing aluminum oxide and had a density of 1.86 g/cm3, close to the density of PFD (ρ = 1.91 g/cm3). This work complements a previous paper (Bowden, N.; Choi, I. S.; Grzybowski, B. A.; Whitesides, G. M. J. Am. Chem. Soc. 1999, 121, 5373) that examined the self-assembly of hexagonal plates of PDMS (ρ = 1.05 g/cm3) that had a density close to that of water, and were attracted through menisci on the hydrophobic faces. The arrays that formed from the heavy (ρ = 1.86 g/cm3) hexagons with a particular pattern of hydrophilic faces were analogous to the arrays that formed fro...



Journal ArticleDOI
TL;DR: It is demonstrated that the pattern of silver particles embedded in the gelatin matrix of exposed and developed silver halide-based photographic film can serve as a template in a broadly applicable method for the microfabrication of metallic microstructures.
Abstract: This paper demonstrates that the pattern of silver particles embedded in the gelatin matrix of exposed and developed silver halide-based photographic film can serve as a template in a broadly applicable method for the microfabrication of metallic microstructures. In this method, a CAD file is reproduced in the photographic film by exposure and developing. The resulting pattern of discontinuous silver grains is augmented and made electrically continuous by electroless deposition of silver, and the electrically continuous structure is then used as the cathode for electrochemical deposition of an additional layer of the same or different metal. The overall process can be completed within 2 h, starting from a CAD file, and can generate electrically continuous structures with the smallest dimension in the plane of the film of ∼30 μm. Structures with aspect ratio of up to 5 can also be obtained by using the metallic structures as photomasks in photolithography using SU-8 photoresist on the top of the electropla...

Journal ArticleDOI
TL;DR: In this paper, three elastomeric optical devices whose optical properties are controlled by distorting the surface topographies of the elastomers were characterized, and the effect of the distortion on the transmissivity of the devices was investigated.
Abstract: We fabricated and characterized three elastomeric optical devices whose optical properties are controlled by distorting the surface topographies of the elastomeric elements. In the force sensor, an applied force distorts the retroreflective corner cube surface pattern increasing the transmissivity of the device. The magnitude and the location of the force can be related to the intensity of the transmitted light. In the thermal light valve, the corner cube topography is distorted thermally; the transmissivity is controlled by the amount of heat delivered to the device. In the elastomeric Fresnel lens, heating of the elastomer results in defocusing of light passing through the lens.

Journal ArticleDOI
15 Apr 2000
TL;DR: A series of well-ordered, extended mesostructures has been generated from hexagonal polyurethane rods by self-assembly using capillary forces using a modification of the surface of one or more sides of the rods rendered hydrophilic by exposure to an oxygen plasma.
Abstract: A series of well-ordered, extended mesostructures has been generated from hexagonal polyurethane rods (15x3.2 mm) by self-assembly using capillary forces. The surface of one or more sides of the rods was rendered hydrophilic by exposure to an oxygen plasma. This modification determined the pattern of hydrophobic and hydrophilic faces; the hydrophobic sides were coated with a thin film of a hydrophobic lubricant. Agitation of the rods in an approximately isodense aqueous environment resulted in their self-assembly, in a process reflecting the action of capillary forces, into an array whose structure depends on the pattern of hydrophobic sides; capillarity also aligned the ends of the rods. We also carried out experiments in reaction chambers that restricted the motion of the rods; this restriction served to increase the size and regularity of the assemblies. Copyright 2000 Academic Press.


Journal ArticleDOI
TL;DR: Auffinger et al. as discussed by the authors presented an analogue model for sequence-specific recognition, using mm-sized objects (analogues of the bases of DNA, or AnBs) floating at the interface between perfluordecalin (PFD) and water and interacting through capillary forces and shape recognition.
Abstract: The formation of double-stranded DNA by recognition of sequences in single-stranded DNA by complementary sequences is fundamental to life. 1 This type of molecular recognition has been studied at every level of detail and realism, from experimental genetics to theoretical statistical mechanics. 2-9 The work described here introduces an analogue model for sequence-specific recognition, using mm-sized objects (analogues of the bases of DNA, or AnBs) floating at the interface between perfluordecalin (PFD) and water and interacting through capillary forces and shape recognition. 10-12 The immediate objective of this work is to abstract the concept of sequence-specific molecular recognition from biology, and use it to join meso-scale objects. Its longerterm objective is to explore the possibility that the recognition of coded sequences will be useful in precision assembly and in the generation of new types of materials from small components. This work is thus an initial exploration of a new strategy for the fabrication of small, structurally complex, non-molecular structures. The AnBs, each 3.2 mm in width and ∼1 mm in thickness, were designed to have shape-selective recognition sites (Scheme 1).13 We used two pairs of AnBs (A ‚B and C‚D) having complementary shapes, in analogy to the A ‚T and G‚C base pairs of DNA; the method could, however, be extended to larger numbers of elements, by analogy to larger numbers with expansions of the four bases used in DNA. 14 The recognition site in each AnB was placed slightly off-center; this asymmetry made sequences of the AnBs asymmetric, and modeled the 5 ′-to-3′ directionality of DNA. The AnBs were connected by a flexible thread ( ∼150 μm thick and 400μm long). The objects were made from poly(dimethylsiloxane) (PDMS), a hydrophobic, elastomeric polymer (Scheme 1). 10 Each strand was designed as a sequence of AnBs using a CAD program. The design was printed onto a transparency using a high-resolution printer.15 When strands longer than 25 AnBs were required, each strand had features at each end that allowed the strands to be connected. 16 Using this transparency as a photomask, a base-relief master was fabricated by photolithography. 17 Casting a prepolymer of PDMS against the master generated an elastomeric replica of this structure. This replica served as a mold with which to generate the desired shapes in PDMS. After removal of the strands of AnBs from the mold, they were dyed to make them easily visible. Designated faces of the pieces were made hydrophilic by oxidation in an oxygen plasma. 10 The faces that were to remain hydrophobic were protected before oxidation by covering them either with Scotch tape or with white correction fluid. After oxidation, the protected surfaces were uncovered 18 and the strands suspended at the interface between water and PFD in a Petri dish. 10 The system was placed on an orbital shaker with a radius of gyration of 19 cm and swirled at a frequency of ω ) 1.0 s-1, using procedures described previously. 10 The two strands paired in 1 -3 * To whom correspondence should be addressed. (1) Watson, J. D.; Crick, F. H. C. Nature1953, 171, 737. (2) Tinoco, I., Jr.J. Phys. Chem. 1996, 100, 13311. (3) Turner, D. H.Curr. Opin. Struct. Biol.1996, 6, 299. (4) Nielsen, P. E.Chem. Eur. J.1997, 3, 505. (5) Seeman, N. C. Angew. Chem., Int. Ed. 1998, 37, 3221. (6) Kool, E. T.Chem. Re V. 1997, 97, 1473. (7) Auffinger, P.; Westhof, E. Curr. Opin. Struct. Biol.1998, 8, 227. (8) Olson, W. K.Curr. Opin. Struct. Biol.1996, 6, 242. (9) Thurston, D. E.; Thompson, A. S. Chem. Br.1990, 767. (10) For a detailed discussion of the PDMS/water/perfluordecalin system as well as the details of experimental techniques, see: Bowden, N.; Choi, I. S.; Grzybowski, B. A.; Whitesides, G. M. J Am. Chem. Soc. 1999, 121, 5373. (11) Bowden, N.; Terfort, A.; Carbeck, J.; Whitesides, G. M. Science1997, 276, 233. (12) Choi, I. S.; Bowden, N.; Whitesides, G. M. J. Am. Chem. Soc. 1999, 121, 1754. (13) The size of the AnBs is large enough to see and manipulate without magnification, and small enough that an interesting number can be incorporated into a single chain and studied in a standard-sized Petri dish. (14) Battersby, T. R.; Ang, D. N.; Burgstaller, P.; Jurzcyk, S. C.; Bowser, M. T.; Buchanan, D. D.; Kennedy, R. T.; Benner, S. A. J. Am. Chem. Soc. 1999, 121, 9781. (15) The transparencies were created using Freehand 8.0 (Macromedia) as drawing program and printed using a 3386 dpi laser image setter. (16) The 3-in. diameter silicon wafers that we used as substrates for photolithography did not allow fabrication of strands of more than 25 AnBs. Longer strands were fabricated by joining several short strands by hand using the dovetail tongue and groove and gluing. (17) Xia, Y.; Whitesides, G. M. Angew. Chem., Int. Ed. 1998, 37, 551. (18) The correction fluid was removed by carefully taking the pieces off the Scotch tape-covered glass slide with tweezers. The dried correction fluid remained stuck to the Scotch tape; separating the strands from this protective film revealed the hydrophobic faces. Scheme 1.Schematic Representation of the Model Design and the Procedures Used to Fabricate the PDMS Strands a

Journal ArticleDOI
TL;DR: In this paper, a method for fabricating 3D microstructures with complex topologiestrefoil, figure eight, and cinquefoil knots, a chain with complex links, Borromean rings, etc.
Abstract: This paper describes a method for fabricating three-dimensional (3D) microstructures with complex topologiestrefoil, figure eight, and cinquefoil knots, a chain with complex links, Borromean rings,...

Journal ArticleDOI
Insung S. Choi1, Marcus Weck1, Bing Xu1, Noo Li Jeon1, George M. Whitesides1 
03 Mar 2000-Langmuir
TL;DR: In this paper, a templated self-assembly based on capillary forces of millimeter-scale poly(dimethylsiloxane) plates suspended at the water−perfluorodecalin interface is described.
Abstract: This paper demonstrates templated self-assemblybased on capillary forcesof millimeter-scale poly(dimethylsiloxane) plates suspended at the water−perfluorodecalin interface. The system described abs...

Proceedings ArticleDOI
01 Jan 2000
TL;DR: In this paper, the use of patterned flows of multiple laminar streams of etching solutions in capillaries to create various topographical features with sizes of 10-200 /spl mu/m in poly(dimethylsiloxane) (PDMS) was described.
Abstract: This paper describes the use of patterned flows of multiple laminar streams of etching solutions in capillaries to create various topographical features with sizes of 10-200 /spl mu/m in poly(dimethylsiloxane) (PDMS). A variety of topographical features were created by using channels with obstacles, by adjusting the flow rates of etchant, or by controlling the duration of etching. Bovine capillary endothelial cells aligned parallel to features when grown inside these topographically patterned capillaries with 10 /spl mu/m ridges. The capillaries with topographical features could also be further patterned with surface-attached red blood cells and surface-adsorbed proteins, using laminar flows. This two-stage patterning produces patterns of proteins and cells on the topography with alignment between the different features and patterns. The technique allows simultaneous micropatterning of multiple cell culture environments using the same capillary system.