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Biomedical subjects

George M Whitesides

Publications and source records attributed to George M Whitesides.

At least 19 recordsLinked to original sources
PubMed2003

Generation of submicrometer structures by photolithography using arrays of spherical microlenses.

This paper describes the fabrication of arrays of spherical microlenses by self-assembly of microspheres and the use of these arrays for nearfield photolithography to generate repetitive microstructures in photoresist. We used these arrays of microspheres to fabricate two types of elastomeric membranes: (i) membranes that have microspheres embedded in their surface and (ii) membranes that have hemispherical wells in their surface. Both types of membranes act as amplitude masks that pattern the intensity of illumination in the near field incident on the photoresist. Microspheres in the first type of membrane act as convergent lenses that generate recessed microstructures in positive photoresist. Hemispherical wells in the second type of membrane act as divergent lenses that produce protrusive microstructures in positive photoresist. This method can generate dense, regular arrays of microstructures with a variety of profiles--circular or hexagonal holes, circular posts, hollow posts, and cones--depending on the sizes and refractive indices of the spherical lenses and the distance between the lenses and the photoresist. This technique provides a simple route to large areas (>4 cm2) of repetitive, simple microstructures.

Journal Article↗
PubMed2003

Cell shape provides global control of focal adhesion assembly.

Cell spreading was controlled independently of the amount and density of immobilized integrin ligand by culturing cells on single adhesive islands of different sizes (100-2500 microm(2)) and shapes (squares, circles, and lines) or on many smaller (3-5 microm diameter) circular islands that were coated with a saturating density of fibronectin and separated by non-adhesive regions. The amount of focal adhesions (FAs) containing vinculin and phosphotyrosine increased in direct proportion to cell spreading under all conditions. FAs localized asymmetrically along the periphery of the small islands that experienced highest tensional stress, and FA staining increased when cytoskeletal tension was stimulated with thrombin, whereas inhibitors of contractility promoted FA disassembly. Thus, these findings demonstrate the existence of an "inside-out" mechanism whereby global cell distortion produces increases in cytoskeletal tension that feed back to drive local changes in FA assembly. This complex interplay between cell morphology, mechanics, and adhesion may be critical to how cells integrate from and function in living tissues.

Actins↗
PubMed2003

Self-assembly of gears at a fluid/air interface.

This paper describes a dynamic system-a system that develops order only when dissipating energy-comprising millimeter to centimeter scale gears that self-assemble into a simple machine at a fluid/air interface. The gears are driven externally and indirectly by magnetic interactions; they are made of poly(dimethylsiloxane) (PDMS) or magnetically doped PDMS, and fabricated by soft lithography. Transfer of torque between gears can take place through three different mechanisms: mechanical interaction, hydrodynamic shear, and capillarity/overlap of menisci. Interplay between these forces allows interactions and motions that are not possible with conventional systems of gears.

Journal Article↗
PubMed2003

Rapid prototyping of 2D structures with feature sizes larger than 8 microm.

This paper extends rapid prototyping for several types of lithography to the 8-25-microm size range, using transparency photomasks prepared by photoplotting. It discusses the technical improvement in photomask quality achieved by photoplotting, compared to the currently used image setting, and demonstrates differences in the resolution that can be obtained with photomasks with features in the 8-100-microm size range. These high-resolution photomasks were used to microfabricate microelectrodes, microlenses, and stamps for microcontact printing, following methods described previously.

Biological Assay↗
PubMed2003

A miniaturized, parallel, serially diluted immunoassay for analyzing multiple antigens.

This paper describes a microfluidic immunoassay that is applicable to the parallel determination of multiple analytes and that requires only a few microliters of sample. This assay relies on a microchannel network that achieves serial dilution of analytes; this network replaces manual dilutions employed in traditional immunoassays and enables the analysis of multiple analytes simultaneously. The immunoassay was demonstrated by an analysis of concentrations of antibodies against the HIV viral proteins gp120 and gp41 in human serum.

Antibodies↗
PubMed2003

Using bifunctional polymers presenting vancomycin and fluorescein groups to direct anti-fluorescein antibodies to self-assembled monolayers presenting d-alanine-d-alanine groups.

This paper describes the synthesis of bifunctional polyacrylamides containing pendant vancomycin (Van) and fluorescein groups, and the use of these polymers to direct antibodies against fluorescein to self-assembled monolayers (SAMs) presenting d-alanine-d-alanine (dAdA) groups. These polymers bind biospecifically to these SAMs via interactions between the dAdA and Van groups and serve as a molecular bridge between the anti-fluorescein antibodies and the SAM. The binding events were characterized using surface plasmon resonance spectroscopy and fluorescence microscopy. The paper demonstrates that polyvalent, biospecific, noncovalent interactions between a polymer and a surface can be used to tailor the properties of the surface in molecular recognition. It also represents a first step toward the design of polymers that direct arbitrarily chosen antibodies to the surfaces of cells.

Acrylic Resins↗
PubMed2003

Propagation of viruses on micropatterned host cells.

We have developed a technique to characterize the in vitro propagation of viruses. Microcontact printing was used to generate linear arrays of alkanethiols on gold surfaces, which served as substrates for the patterned culture of baby hamster kidney (BHK-21) cells. Vesicular stomatitis virus (VSV) was added to unpatterned cell reservoirs adjacent to the patterned cells and incubated, setting in motion a continuously advancing viral infection into the patterned cells. At different incubation times, multiple arrays were chemically fixed to stop the viral propagation. Viral propagation distances into the patterned cells were determined by indirect immunofluorescent labeling and visualization of the VSV surface glycoprotein (G). The infection spread at approximately 50 microm/h in the 140-microm lines. Moreover, different temporal stages of the infection process were simultaneously visualized along individual lines. These stages included initiation of infection, based on G protein expression; cell-cell fusion, based on virus-induced clustering of cell nuclei; and cytoskeletal degradation, based on localized release of cells from the surface. This work sets a foundation for parallel, high-throughput characterization of viral and cellular processes.

Animals↗
PubMed2003

Formation and structure of self-assembled monolayers of alkanethiolates on palladium.

The adsorption of n-alkanethiols onto polycrystalline thin films of palladium containing a strong (111) texture produces well-organized, self-assembled monolayers. The organization of the alkane chains in the monolayer and the nature of the bonding between the palladium and the thiol were studied by contact angle measurements, optical ellipsometry, reflection absorption infrared spectroscopy (RAIRS), and X-ray photoelectron spectroscopy (XPS). The XPS data reveals that a compound palladium-sulfide interphase is present at the surface of the palladium film. The RAIR spectra, ellipsometry data, and wetting properties show that the palladium-sulfide phase is terminated with an organized, methyl-terminated monolayer of alkanethiolates. The local molecular environment of the alkane chains transitions from a conformationally disordered, liquidlike state to a mostly all-trans, crystalline-like structure with increasing chain length (n = 8-26). The intensities and dichroism of the methylene and methyl stretching modes support a model for the average orientation of an ensemble of all-trans-conformer chains with a tilt angle of approximately 14-18 degrees with respect to the surface normal and a twist angle of the CCC plane relative to the tilt plane of approximately 45 degrees. The SAMs are stable in air, although the sulfur present at the surface oxidizes in air over a period of 2-5 days at room temperature. The differences in chain organization between SAMs formed by microcontact printing and by solution deposition are also examined by RAIRS and XPS.

Air↗
PubMed2003

Electrochemical desorption of self-assembled monolayers noninvasively releases patterned cells from geometrical confinements.

This report describes a method to pattern mammalian cells using self-assembled monolayers (SAMs), and then to use electrochemical desorption of these monolayers to release cells from their patterns. This method uses an oligo(ethyleneglycol)-terminated SAM to prevent,-and a methyl-terminated SAM to allow-adsorption of proteins and attachment of bovine capillary endothelial cells. Electrochemical removal of the oligo(ethyleneglycol)-terminated SAM allowed proteins to adsorb onto areas that had been previously inert and enabled cells to migrate into these areas. This straightforward technique is useful in bioassays for drug screening and for fundamental studies in cell biology.

Animals↗
PubMed2003

Dynamic self-assembly of rings of charged metallic spheres.

This Letter describes dynamic self-assembly in a system of stainless steel spheres ( approximately 1 mm in diameter) rolling on a flat dielectric surface under the influence of an external magnetic field that rotates parallel to the plane of the surface. As the spheres move, they charge triboelectrically. Self-assembly is mediated by two types of electrostatic interactions among these charges: (i) attraction between negatively charged regions of the surface and positively charged spheres and (ii) repulsion between the like-charged spheres. The spheres organize into highly ordered rings as a result of these electrostatic interactions.

Journal Article↗
PubMed2003

Fabrication of complex three-dimensional microchannel systems in PDMS.

This paper describes a method for fabricating three-dimensional (3D) microfluidic channel systems in poly(dimethylsiloxane) (PDMS) with complex topologies and geometries that include a knot, a spiral channel, a "basketweave" of channels, a chaotic advective mixer, a system with "braided" channels, and a 3D grid of channels. Pseudo-3D channels, which are topologically equivalent to planar channels, are generated by bending corresponding planar channels in PDMS out of the plane into 3D shapes. True 3D channel systems are formed on the basis of the strategy of decomposing these complex networks into substructures that are planar or pseudo-3D. A methodology is developed that connects these planar and/or pseudo-3D structures to generate PDMS channel systems with the original 3D geometry. This technique of joining separate channel structures can also be used to create channel systems in PDMS over large areas by connecting features on different substrates. The channels can be used as templates to form 3D structures in other materials.

Dimethylpolysiloxanes↗
PubMed2003

Selective chemical treatment of cellular microdomains using multiple laminar streams.

There are many experiments in which it would be useful to treat a part of the surface or interior of a cell with a biochemical reagent. It is difficult, however, to achieve subcellular specificity, because small molecules diffuse distances equal to the extent of the cell in seconds. This paper demonstrates experimentally, and analyzes theoretically, the use of multiple laminar fluid streams in microfluidic channels to deliver reagents to, and remove them from, cells with subcellular spatial selectivity. The technique made it possible to label different subpopulations of mitochondria fluorescently, to disrupt selected regions of the cytoskeleton chemically, to dislodge limited areas of cell-substrate adhesions enzymatically, and to observe microcompartmental endocytosis within individual cells. This technique does not require microinjection or immobilization of reagents onto nondiffusive objects; it opens a new window into cell biology.

Animals↗
PubMed2003

Controlling flows in microchannels with patterned surface charge and topography.

This Account reviews two procedures for controlling the flow of fluids in microchannels. The first procedure involves patterning the density of charge on the inner surfaces of a channel. These patterns generate recirculating electroosmotic flows in the presence of a steady electric field. The second procedure involves patterning topography on an inner surface of a channel. These patterns generate recirculation in the cross-section of steady, pressure-driven flows. This Account summarizes applications of these flow to mixing and to controlling dispersion (band broadening).

Journal Article↗
PubMed2003

Electrostatic self-assembly of macroscopic crystals using contact electrification.

Self-assembly of components larger than molecules into ordered arrays is an efficient way of preparing microstructured materials with interesting mechanical and optical properties. Although crystallization of identical particles or particles of different sizes or shapes can be readily achieved, the repertoire of methods to assemble binary lattices of particles of the same sizes but with different properties is very limited. This paper describes electrostatic self-assembly of two types of macroscopic components of identical dimensions using interactions that are generated by contact electrification. The systems we have examined comprise two kinds of objects (usually spheres) made of different polymeric materials that charge with opposite electrical polarities when agitated on flat, metallic surfaces. The interplay of repulsive interactions between like-charged objects and attractive interactions between unlike-charged ones results in the self-assembly of these objects into highly ordered, closed arrays. Remarkably, some of the assemblies that form are not electroneutral-that is, they possess a net charge. We suggest that the stability of these unusual structures can be explained by accounting for the interactions between electric dipoles that the particles in the aggregates induce in their neighbours.

Caprolactam↗
PubMed2002

Dissections: self-assembled aggregates that spontaneously reconfigure their structures when their environment changes.

This Communication describes a new strategy for the design of adaptive structures based on reconfigurable mesoscale self-assembly. Several sets of millimeter-scale objects have been designed that can self-assemble into two different, regular aggregates at the interface between an aqueous solution and perfluorodecalin; the choice between the two aggregates is determined by the density of the aqueous phase.

Journal Article↗
PubMed2002

Using hierarchical self-assembly to form three-dimensional lattices of spheres.

This paper describes an approach to the fabrication of three-dimensional (3-D) structures of millimeter-scale spherical beads having a range of lattices-tetragonal, cubic, and hexagonal-using hierarchical self-assembly. The process has five steps: (i) metal-coated beads are packed in a rod-shaped cavity in an elastomeric polymer (poly(dimethylsiloxane), PDMS); (ii) the beads are embedded in a second polymer (PDMS or polyurethane, PU) using a procedure that leaves the parts of the beads in contact with the PDMS exposed; (iii) the exposed areas of the beads are coated with a solder having a low melting point; (iv) the polymer rods-with embedded beads and exposed solder drops-are suspended in an approximately isodense medium (an aqueous solution of KBr) and allowed to self-assemble by capillary interactions between the drops of molten solder; and (v) the assembly is finished by several procedures, including removing the beads from the polymer matrix by dissolution, filling the voids left with another material, and dissolving the matrix. The confinement of the beads in regular structures in polymer rods makes it possible to generate self-assembled structures with a variety of 3-D lattices; the type of the lattice formed can be controlled by varying the size of the beads, and the size and shape of the cross-section of the rods.

Journal Article↗