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Showing papers by "George M. Whitesides published in 2004"


Journal ArticleDOI
TL;DR: In this paper, a method for generating monodisperse gaseous bubbles in a microfluidic flow-focusing device is described, where bubbles self-assemble into highly ordered, flowing lattices.
Abstract: This letter describes a method for generating monodisperse gaseous bubbles in a microfluidic flow-focusing device. The bubbles can be obtained in a range of diameters from 10 to 1000μm. The volume Vb of the bubbles scales with the flow rate q and the viscosity μ of the liquid, and the pressure p of the gas stream as Vb∝p∕qμ. This method allows simultaneous, independent control of the size of the individual bubbles and volume fraction of the dispersed phase. Under appropriate conditions, bubbles self-assemble into highly ordered, flowing lattices. Structures of these lattices can be adjusted dynamically by changing the flow parameters.

655 citations


Journal ArticleDOI
19 Nov 2004-Langmuir
TL;DR: The influence of the composition of poly(dimethylsiloxane) (PDMS) on the attachment and growth of several different types of mammalian cells: primary human umbilical artery endothelial cells (HUAECs), transformed 3T3 fibroblasts, transformed osteoblast-like MC3T3-E1 cells, and HeLa (transformed epithelial) cells is described.
Abstract: This paper describes the influence of the composition of poly(dimethylsiloxane) (PDMS) on the attachment and growth of several different types of mammalian cells: primary human umbilical artery endothelial cells (HUAECs), transformed 3T3 fibroblasts (3T3s), transformed osteoblast-like MC3T3-E1 cells, and HeLa (transformed epithelial) cells. Cells grew on PDMS having different ratios of base to curing agent: 10:1 (normal PDMS, PDMSN), 10:3 (PDMSCA), and 10:0.5 (PDMSB). They were also grown on “extracted PDMS” (normal PDMS that has reduced quantities of low molecular-weight oligomers, PDMSN,EX) and normal PDMS that had been extracted and then oxidized (PDMSN,EX,OX); all surfaces were exposed to a solution of fibronectin prior to cell attachment. Generally, fibronectin-coated PDMS is a suitable substrate for culturing mammalian cells. Compatibility of cells on some surfaces, however, was dependent on the cell type: PDMSN,EX,OX caused cell detachment of 3T3 fibroblasts and MC3T3-E1 cells, and PDMSCA caused...

383 citations


Journal ArticleDOI
TL;DR: This paper describes an integrated approach to a miniaturized immunoassay called a “POCKET immunoASSay” (“PockET” is short for portable and cost-effective) that has the potential to be inexpensive and operable with minimal equipment and technical skills.
Abstract: The development of technology for use in resource-poor countries encounters a specific type of challenge not ordinarily faced in academic science: the technology must be inexpensive and it must work with minimal infrastructure. This challenge is particularly severe when the problems being solved are, by their nature, ones that require high-technology solutions. For these kinds of problems, the elegance of the solutions must lie in the use of science to guide the assembly of readily available components into a simple, workable, and well-integrated package. In this paper, we describe an integrated approach to a miniaturized immunoassay called a “POCKET immunoassay” (“POCKET” is short for portable and cost-effective). This immunoassay has, we believe, the potential to be inexpensive and operable with minimal equipment and technical skills, and shows an analytical performance approaching that of enzyme-linked immunosorbent assays (ELISA) performed in a bench-top format in clinical laboratories. A top priority for improving health in developing countries is technology for simple, affordable diagnosis of infectious diseases. Immunoassays such as ELISA are the most reliable and widely used methods for detecting antigens and antibodies, but they require expensive and bulky instruments for optical detection, hours of incubation for diffusionlimited reactions on the surface, and many steps of pipetting. 3] These constraints prevent the use of ELISA in settings that require low-cost or compact equipment, and in environments that lack electricity or trained personnel. One application with these requirements is the detection of infectious diseases in the field in developing countries; 4,5] other potential uses include point-of-care diagnostics by first responders and in health clinics, and detection of biological warfare agents in the field. Immunochromatographic assays (also known as “strip tests” and “lateral-flow

331 citations


Journal ArticleDOI
TL;DR: Single-mode and multi-mode waveguiding, switching and tunable evanescent coupling between liquid cores and cladding fluid is demonstrated.
Abstract: This report describes the manipulation of light in waveguides that comprise a liquid core and a liquid cladding (liq/liq waveguide). These waveguides are dynamic: Their structure and function depend on a continuous, laminar flow of the core and cladding liquids. Because they are dynamic, they can be reconfigured and adapted continuously in ways that are not possible with solid-state waveguides. The liquids are introduced into the channels of a microfluidic network designed to sandwich the flowing core liquid between flowing slabs of the cladding fluid. At low and moderate Reynolds numbers, flow is laminar, and the liq/liq interfaces are optically smooth. Small irregularities in the solid walls of the channels do not propagate into these interfaces, and liq/liq waveguides therefore exhibit low optical loss because of scattering. Manipulating the rate of flow and the composition of the liquids tunes the characteristics of these optical systems.

297 citations


Journal ArticleDOI
TL;DR: The trapped particle and location of the magnetic trap can be translated in three dimensions by independent manipulation of the permanent magnets and characterizes the biocompatibility of the trapping solution.
Abstract: This manuscript describes the fabrication and use of a three-dimensional magnetic trap for diamagnetic objects in an aqueous solution of paramagnetic ions; this trap uses permanent magnets. It demonstrates trapping of polystyrene spheres, and of various types of living cells: mouse fibroblast (NIH-3T3), yeast (Saccharomyces cerevisiae), and algae (Chlamydomonas reinhardtii). For a 40mM solution of gadolinium (III) diethylenetriaminepentaacetic acid (Gd·DTPA) in aqueous buffer, the smallest cell (particle) that could be trapped had a radius of ∼2.5μm. The trapped particle and location of the magnetic trap can be translated in three dimensions by independent manipulation of the permanent magnets. This letter a1so characterizes the biocompatibility of the trapping solution.

173 citations


Journal ArticleDOI
09 Sep 2004-Langmuir
TL;DR: The ability to produce multiple, aligned patterns ofSAMs in a single step, without alignment of photomasks in separate steps, increases the versatility of SAMs for studying a range of physical phenomena.
Abstract: This work describes a method for patterning a gold substrate with multiple, aligned self-assembled monolayers (SAMs) using light at different wavelengths. It describes the synthesis and characterization of an alkanethiolate SAM that is photosensitive to light at both 220 and 365 nm. A photomask acts as an area-selective filter for light at 220 and 365 nm, and a single set of exposures at these two wavelengths through one photomask, without steps of alignment between the exposures, can produce three aligned SAMs on one gold substrate. We demonstrate the versatility of this method of photopatterning by modifying individual aligned SAMs chemically to produce surfaces having different properties. We characterize the modified SAMs using immunolabeling, matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy, and surface plasmon resonance spectroscopy. We also describe the patterning of two aligned SAMs that resist the adsorption of proteins and a third region that does not resist the adsorption of proteins. The ability to produce multiple, aligned patterns of SAMs in a single step, without alignment of photomasks in separate steps, increases the versatility of SAMs for studying a range of physical phenomena.

152 citations


Journal ArticleDOI
TL;DR: Deformation patterns of the cytoskeleton and the nucleolus were sensitive to loading direction, suggesting anisotropic mechanical signaling, and suggest that mechanical anisotropy originates from intrinsic cytoskeletal tension within the stress fibers.
Abstract: We describe a three-dimensional magnetic twisting device that is useful in characterizing the mechanical properties of cells. With the use of three pairs of orthogonally aligned coils, oscillatory mechanical torque was applied to magnetic beads about any chosen axis. Frequencies up to 1 kHz could be attained. Cell deformation was measured in response to torque applied via an RGD-coated, surface-bound magnetic bead. In both unpatterned and micropatterned elongated cells on extracellular matrix, the mechanical stiffness transverse to the long axis of the cell was less than half that parallel to the long axis. Elongated cells on poly-L-lysine lost stress fibers and exhibited little mechanical anisotropy; disrupting the actin cytoskeleton or decreasing cytoskeletal tension substantially decreased the anisotropy. These results suggest that mechanical anisotropy originates from intrinsic cytoskeletal tension within the stress fibers. Deformation patterns of the cytoskeleton and the nucleolus were sensitive to loading direction, suggesting anisotropic mechanical signaling. This technology may be useful for elucidating the structural basis of mechanotransduction.

141 citations


Journal ArticleDOI
TL;DR: A method for repetitive and rapid formation of planar microarrays and gradients of proteins using patterned agarose stamps is described and applied to surface‐based immunoassays.
Abstract: We describe a method for repetitive and rapid formation of planar microarrays and gradients of proteins using patterned agarose stamps. It demonstrates: (i) micropatterning of agarose gels with feature sizes as small as 2 microm; (ii) inking of posts (diameter 50-1000 microm) on patterned agarose stamps with one or multiple (here, eight) proteins and repetitive stamping of patterns (>100 times in the case of one protein) and arrays (20 times in the case of eight proteins) without the need for intermediate re-inking; (iii) transferring spots of proteins with good homogeneity in surface coverage to glass slides; (iv) applying this technique to surface-based immunoassays; (v) stamping that requires only sub-nanomolar amounts of protein (typically approximately 3 microg in approximately 0.6 microL of solution); (vi) stamping without the need for drying of the proteins, as opposed to stamping with stamps made of poly(dimethylsiloxane); and (vii) patterning gradients of proteins by allowing two proteins to diffuse toward each other in an agarose stamp, followed by printing the protein gradients onto a surface.

137 citations


Patent
20 Feb 2004
TL;DR: In this paper, a microfluidic system including a first fluid path and a second fluid path are separated by a first convection controller at a first contact region, where at least one of the first and the second fluid paths has a cross-sectional dimension of less than about 1 millimeter.
Abstract: The present invention relates to fluidic systems and, in particular, fluidic arrays and methods for using them to promote interaction of materials. In one embodiment, the present invention is directed to a microfluidic system. The microfluidic system includes a first fluid path and a second fluid path segregated from the first fluid path by a first convection controller at a first contact region, wherein at least one of the first fluid path and the second fluid path has a cross-sectional dimension of less than about 1 millimeter. In another aspect, the present invention is directed to a method of promoting interaction. In another aspect, the invention relates to a device and method for performing titrations.

116 citations


Journal ArticleDOI
TL;DR: In this paper, a study of the kinetics of contact charging resulting from the rolling of millimeter-sized metallic spheres on flat surfaces of polystyrene (PS) is presented.
Abstract: This report is a study of the kinetics of contact charging resulting from the rolling of millimeter-sized metallic spheres on flat surfaces of polystyrene (PS). Charging was studied (i) for different values of the relative humidity (RH) of the air in contact with the system, (ii) in acidic and basic atmospheres, and (iii) for a series of PS surfaces oxidized to different degrees. The rates of charging increased with increasing RH; they were higher in basic atmospheres than in neutral or acidic ones and correlated with the numbers of hydrophilic groups on the surface of the polymer. These findings are consistent with a mechanism that implicates a thin film of water on the surface of PS as an important element of tribocharging in this system.

112 citations


Patent
29 Dec 2004
TL;DR: In this paper, the authors describe a method for detecting the presence of a metallic layer by visual inspection or by measuring light transmission through the layer, conductivity or resistance of the layer or metal concentration in the metal solution after flowing a metal solution over the surface.
Abstract: An assay method is described, which comprises the steps of immobilizing a binding partner (e.g., an antigen or antibody) for an analyte to be detected (e.g., an antibody or antigen) on a portion (140) of a surface (130) of a microfluidic chamber (120,122,124); passing a fluid sample over the surface and allowing the analyte to bind to the binding partner; allowing a metal colloid, e.g., a gold-conjugated antibody, to associate with the bound analyte; flowing a metal solution, e.g., a silver solution, over the surface such as to form an opaque metallic layer; and detecting the presence of said metallic layer, e.g., by visual inspection or by measuring light transmission through the layer, conductivity or resistance of the layer, or metal concentration in the metal solution after flowing the metal solution over the surface.


Journal ArticleDOI
TL;DR: This Communication describes the fabrication of planar structures comprising metallic features with nanometer-scale lateral dimensions in polymer prepared by sectioning a thin metallic film, embedded in a polymer matrix, in a plane perpendicular to the metallic film.
Abstract: This Communication describes the fabrication of planar structures comprising metallic features with nanometer-scale lateral dimensions in polymer prepared by sectioning a thin metallic film, embedded in a polymer matrix, in a plane perpendicular to the metallic film. This procedure converts a structure that is thin along the z-axis into a structure that is thin along the x-axis. The embedded thin metal film is still conductive and can be used as a nanoelectrode. The structure and composition of the exposed nanoedge can be easily tuned by changing the structure of the surface supporting the metal film, and the composition and the thickness of that film.

Journal ArticleDOI
TL;DR: Here is the first example of a metal–molecule–metal junction comprising two closely spaced alkane thiolate monolayers, and a few examples are now known in which two or more metal redox centers organized in space and energy with respect to one another display electronic functions such as rectification and switching.
Abstract: Studies of electron transport through molecules using metal– molecule–metal junctions or scanning probe devices suggest principles that may be useful in designing systems for organic/organometallic electronics. Molecules are, in general, poor conductors of electrons, and “conduct” by tunneling. For some molecules, however, applying a potential across the electrodes of a metal–molecule–metal junction can cause an orbital (usually the HOMO or LUMO) of the molecule to fall between the Fermi levels of the electrodes and thus increase conductivity. 8] Molecules with well-defined and readily accessible redox states are, thus, attractive candidates for use in testing theories of electron transport (and perhaps for electronic devices), and a few examples are now known in which two or more metal redox centers organized in space and energy with respect to one another display electronic functions such as rectification and switching. Here we report the first example of a metal–molecule–metal junction comprising two closely spaced alkane thiolate monolayers,

Journal ArticleDOI
TL;DR: Clusters of gold nanoparticles are grown from templates formed from the self-assembly of immunoglobulin Gs by using a synthetic divalent antigen using Carbohydrates inherent to IgGs for the electroless deposition of gold.
Abstract: Immunoglobulin G templates: Clusters of gold nanoparticles are grown (see picture) from templates formed from the self-assembly of immunoglobulin Gs (IgGs) by using a synthetic divalent antigen. Carbohydrates inherent to IgGs create local nucleation centers for the electroless deposition of gold.

Journal ArticleDOI
16 May 2004
TL;DR: In this paper, the authors describe the fabrication by electrical microcontact printing of optical waveguides and splitters made of poly(4-vinylphenol) doped with phloxine B, permitting inexpensive, rapid prototyping over large areas and construction of integrated, multi-level devices.
Abstract: We describe the fabrication by electrical microcontact printing of optical waveguides and splitters made of poly(4-vinylphenol) doped with phloxine B, permitting inexpensive, rapid prototyping over large areas and construction of integrated, multi-level devices.

Journal ArticleDOI
TL;DR: Self-assembled monolayers on palladium that resist the nonspecific adsorption of proteins and the adhesion of mammalian cells are described.
Abstract: This paper describes self-assembled monolayers (SAMs) on palladium that resist the nonspecific adsorption of proteins and the adhesion of mammalian cells. These SAMs form when thin films of palladi...

Journal ArticleDOI
TL;DR: In this paper, the authors describe dynamic self-assembly of two-component rotors floating at the interface between liquid and air into simple, reconfigurable mechanical systems (machines).
Abstract: This letter describes dynamic self-assembly of two-component rotors floating at the interface between liquid and air into simple, reconfigurable mechanical systems (“machines”). The rotors are powered by an external, rotating magnetic field, and their positions within the interface are controlled by: (i) repulsive hydrodynamic interactions between them and (ii) by localized magnetic fields produced by an array of small electromagnets located below the plane of the interface. The mechanical functions of the machines depend on the spatiotemporal sequence of activation of the electromagnets.

Journal ArticleDOI
30 Dec 2004
TL;DR: Ciferri et al. as discussed by the authors reviewed the synthesis and structures of self-assembled monolayers (SAMs) on gold and silver, along with chemical reactions that occur on SAMs after their assembly.
Abstract: A polymer is a macromolcule made up of multiple equivalents of one or more monomers linked together by covalent bonds. Self‐assembled monolayers (SAMs) are highly ordered molecular assemblies formed by chemisorption of functionalized molecules on the surface. Various system of SAMs are reviewed in this article. The synthesis and structures of SAMs on gold and silver are briefly discussed along with chemical reactions that occur on SAMs after their assembly. The patterning of SAMs on gold and its applications are discussed in the plane of the monolayer. #Reprinted from Supramolecular Polymers, Ciferri, A., Ed., Marcel Dekker, Inc.: New York, 2000; 435–470.

Journal ArticleDOI
TL;DR: A microfluidic device, fabricated in poly(dimethylsiloxane), that is used for potentiometric titrations that generates step gradients of redox potentials in a series of microchannels is described.
Abstract: This paper describes a microfluidic device, fabricated in poly(dimethylsiloxane), that is used for potentiometric titrations. This system generates step gradients of redox potentials in a series of microchannels. These potentials are probed by microelectrodes that are integrated into the chip; the measured potentials were used to produce a titration curve from which the end point of a reaction was measured.

Journal ArticleDOI
TL;DR: Capillary electrophoresis demonstrates that the Zn(II) cofactor is not required for refolding into a nativelike conformation, does not remain associated with the unfolded protein, and does not significantly change the rate of refolding.
Abstract: This paper uses capillary electrophoresis to follow a globular metalloproteinbovine carbonic anhydrase II (BCA, EC 4.2.1.1)on unfolding upon treatment with sodium dodecyl sulfate (SDS) and refolding upon removal of SDS, both in the presence and the absence of its Zn(II) cofactor. This research demonstrates that the Zn(II) cofactor is not required for refolding into a nativelike conformation, does not remain associated with the unfolded protein, and does not significantly change the rate of refolding. The presence of the Zn(II) cofactor, however, does increase the total amount of recovered protein by a factor of 2. Capillary electrophoresis could distinguish between native and denatured protein, based on the difference in electrophoretic mobility between the native protein and the aggregate of denatured protein and SDS. In addition, the active site was probed by observing binding of BCA to a charged arylsulfonamide using affinity capillary electrophoresis. These studies provide a foundation for future phys...

Journal ArticleDOI
TL;DR: In this paper, a technique for fabricating three-dimensional, metallic, pyramidal microstructures with base dimensions of 1−2 μm, wall thickness of ∼100−200 nm, and tip-curvature radius of ∼50 nm is described.
Abstract: This paper describes a technique for fabricating three-dimensional, metallic, pyramidal microstructures with base dimensions of 1−2 μm, wall thicknesses of ∼100−200 nm, and tip-curvature radius of ∼50 nm. The procedure begins with the fabrication of pyramidal pits in the surface of an n-doped silicon substrate. An electrically insulating surface layer of SiO2 covers the regions outside the pits. These pits are patterned using either conventional photolithography or soft lithography and formed by selective anisotropic etching. The resulting topographically patterned silicon serves as the cathode for the selective electrodeposition of metal in the pyramidal pits. Removing the silicon template by etching generates free-standing, pyramidal, metallic microstructures.


Journal ArticleDOI
TL;DR: Tipping large arrays of micrometer-scale dominos onto their side generates complex 3D topographies and arrays of nanoscale electrodes that collapse in parallel when a shearing force is applied uniformly to an array of free-standing pillars.
Abstract: Communications Tipping large arrays of micrometer-scale dominos onto their side generates complex 3D topographies and arrays of nanoscale electrodes. These microdominos collapse in parallel when a shearing force is applied uniformly to an array of free-standing pillars. For more information, see the Communication by G. M. Whitesides and co-workers on the following pages.

Journal ArticleDOI
TL;DR: In this paper, a series of self-assembled monolayers (SAMs) are sandwiched between two metal electrodes, i.e., metal (mercury) −SAM//SAM-metal junctions.

Patent
29 Jan 2004
TL;DR: In this article, a series of methods, compositions, and articles for altering a property of a surface by exposing at least a portion of the surface to a non-chemical, force-creating field and/or force, such as an electric field.
Abstract: The present invention provides a series of methods, compositions, and articles for altering a property of a surface (for example, the cytophilicity and/or the hydrophilicity), by exposing at least a portion of the surface to a non-chemical, force-creating field and/or force, such as an electric field. The field/force may be created by any suitable technique. For instance, the field can be created by applying a voltage across the surface, by electrical induction, etc. In certain embodiments, the surface includes molecules attached thereto that can be detached when exposed to non-chemical, force-creating fields and/or forces, thereby altering the chemical composition of at least a portion of the surface. In one set of embodiments, the molecules attached to the surface may include molecules forming a self-assembled monolayer on the surface. In some embodiments, the molecules attached to the surface may include thiol moieties (e.g., as in an alkanethiol), by which the molecule can become attached to the surface. In certain cases, the molecules may be terminated at the unattached end with one or more hydrophilic groups, for example, unmodified ethylene glycol moieties. In some cases, the molecules attached to the surface may include one or more moieties that can bind to various entities such as proteins, peptides, nucleic acids, drugs, cells, etc. In certain embodiments, the techniques are used to enable novel assays for cell motility and/or spreading and screening tests for determining drugs and/or treatments effective in increasing or decreasing cell shape changes and/or motility on surfaces.

Journal ArticleDOI
TL;DR: A model Hamiltonian is proposed for such indirect electron exchange involving two intermediate species and can be used to determine the energy of reorganization associated with the electron transfer.
Abstract: Experimental data for electron exchange between two electrodes covered by electroactive films are presented and discussed in terms of the Gerischer model. A model Hamiltonian is proposed for such indirect electron exchange involving two intermediate species. Explicit model calculations are performed for the case in which the coupling between the two adsorbates is weak and determines the overall rate. The calculations agree well with the experimental data, and can be used to determine the energy of reorganization associated with the electron transfer.

Patent
14 Apr 2004
TL;DR: In this paper, a system is provided for positioning separate portions of a sample in elongate, parallel channels of the sample chamber and irradiating the sample in the chamber to create a diffraction pattern where the sample and the chamber differ in refractive index.
Abstract: A system is provided for positioning separate portions of a sample in elongate, parallel channels of a sample chamber and for irradiating a sample in the chamber to create a diffraction pattern where the sample and chamber differ in refractive index. The system also can measure absorption of electromagnetic radiation by a sample in the chamber, and can measure the absorption simultaneously with measurement of diffraction by the sample.


Patent
24 Aug 2004
TL;DR: In this paper, a method for 3D microstructures with integral features less than about 1 mm was proposed, where the deformation along these deformable portions, e.g., bending, can be applied to create a third dimension.
Abstract: The present invention relates to three-dimensional microstructures and methods for making these microstructures, particularly microstructures having integral features less than about 1 mm. Examples of these microstructures include trusses. The microstructures can be prepared from two-dimensional structures having a deformable portion. Thus, by applying a deformation along these deformable portions, e.g. bending, a third-dimension can be created. The deformable portions can comprise thinner dimensions than more rigid portions to allow facile deformation to a predetermined angle or orientation. Electroplating at least a portion of the three-dimensional microstructure with a metal coating allows the formation of integral features in addition to covering any defects formed by the deformation and/or strengthening any thin components. The initial two-dimensional microstructure can be prepared by various patterning methods such as soft lithographic methods.