Connectivity of features in microlens array reduction photolithography: generation of various patterns with a single photomask

Microlens array photolithography (MAP) is a technique in which arrays of microlenses positioned close to photoresist reduce cm-sized figures on photomasks and form mum-scale images in the photoresist. This work demonstrates that MAP, using a single photomask, can generate patterns having different symmetries and periodicities from that of the lens array. This capability of MAP depends on (i) the connectivity between the images produced by individual microlenses and (ii) the orientation of the photomask relative to the lens array prior to exposure. By changing this orientation, MAP, using a single mask and a single array of microlenses, could be used to generate patterns that (i) are separated from each other, (ii) overlap with each other, (iii) are 2D chiral, and thus different from both the lens array and the mask in symmetry, (iv) have a symmetry reduced from that of the lens array, or (v) have a smaller unit cell and smaller pitch than that of the lens array.     

What Will Chemistry Do in the Next Twenty Years?

The path of chemistry in the future will be determined both by its participation in solving large-scale societal problems and by its generation of new ideas through basic research. This article sketches four of the areas of societal “pull” in which chemistry will play a role in solving applied problems—national security, health care, the environment, and energy—and four areas in which basic research will be especially fruitful—materials chemistry, biological chemistry, computational chemistry, and chemistry exploring the limits of size and speed in chemical phenomena.     

Design of three-dimensional, millimeter-scale models for molecular folding.

This communication describes the fabrication of three-dimensional structures of organic polymers using principles of design inspired by protein folding. The structures consist of rigid polyhedral components with dimensions of a few millimeters ("microdomains"), representing alpha-helical and beta-sheet secondary structures, connected with flexible linkers representing loops or turns. These structures were fabricated from polyurethane using photolithographic and soft lithographic techniques. The surfaces of the microdomains were patterned into hydrophobic and hydrophilic regions, and a hydrophobic photocurable liquid (serving both as lubricant and adhesive) was selectively precipitated onto the hydrophobic areas. The unfolded structures were suspended in water and agitated by tumbling. Self-assembly occurred through coalescence of the thin films of hydrophobic liquid, and was caused by minimization of the free energy of the interface between the liquid adhesive and the water. The self-assembled structures were locked in place by curing the adhesive with UV light. These results demonstrate the use of concepts abstracted from the study of proteins-including attractive hydrophobic interactions, shape complementarity, and conformational constraint-in the self-assembly of complex, three-dimensional structures on the millimeter scale.     

A miniaturized arrayed assay format for detecting small molecule-protein interactions in cells

Background: Two complementary approaches to studying the cellular function of proteins involve alteration of function either by mutating protein-encoding genes or by binding a small molecule to the protein. A mutagen can generate millions of genetic mutations; correspondingly, split-pool synthesis can generate millions of unique ligands attached to individual beads. Genetic screening of mutations is relatively straightforward but, in contrast, split-pool synthesis presents a challenge to current methods of screening for compounds that alter protein function. The methods used to screen natural products are not feasible for large libraries composed of covalently immobilized compounds on synthesis beads. The sheer number of compounds synthesized by split-pool synthesis, and the small quantity of individual compound attached to each bead require assay miniaturization for efficient screening.Results: We present a miniaturized cell-based technique for the screening of ligands prepared by split-pool synthesis. Spatially defined droplets with uniform volumes of approximately 50–150 nanoliters (depending on well dimensions) are arrayed on plastic devices prepared using a combination of photolithography and polymer molding. Using this microtechnology, approximately 6,500 assays using either yeast cells or mammalian tissue culture can be performed within the dimensions of a standard 10 cm petri dish. We demonstrate that the biological effect of a small molecule prepared by split-pool synthesis can be detected in this format following its photorelease from a bead.Conclusions: The miniaturized format described here allows uniformly sized nanodroplets to be arrayed on plastic devices. The design is amenable to a large number of biological assays and the spatially arrayed format ensures uniform and controlled ligand concentrations and should facilitate automation of assays. The screening method presented here provides an efficient means of rapidly screening large numbers of ligands made by split-pool synthesis in both yeast and mammalian cells.     

Chemical force spectroscopy in heterogeneous systems: intermolecular interactions involving epoxy polymer,mixed monolayers,and polar solvents

We used chemical force microscopy (CFM) to study adhesive forces between surfaces of epoxy resin and self-assembled monolayers (SAMs) capable of hydrogen bonding to different extents. The influence of the liquid medium in which the experiments were carried out was also examined systematically. The molecular character of the tip, polymer, and liquid all influenced the adhesion. Complementary macroscopic contact angle measurements were used to assist in the quantitative interpretation of the CFM data. A direct correlation between surface free energy and adhesion forces was observed in mixed alcohol-water solvents. An increase in surface energy from 2 to 50 mJ/m(2) resulted in an increase in adhesion from 4-8 nN to 150-300 nN for tips with radii of 50-150 nm. The interfacial surface energy for identical nonpolar surface groups of SAMs was found not to exceed 2 mJ/m(2). An analysis of adhesion data suggests that the solvent was fully excluded from the zone of contact between functional groups on the tip and sample. With a nonpolar SAM, the force of adhesion increased monotonically in mixed solvents of higher water content; whereas, with a polar SAM (one having a hydrogen bonding component), higher water content led to decreased adhesion. The intermolecular force components theory was used for the interpretation of adhesion force measurements in polar solvents. Competition between hydrogen bonding within the solvent and hydrogen bonding of surface groups and the solvent was shown to provide the main contribution to adhesion forces. We demonstrate how the trends in the magnitude of the adhesion forces for chemically heterogeneous systems (solvents and surfaces) measured with CFM can be quantitatively rationalized using the surface tension components approach. For epoxy polymer, inelastic deformations also contributed heavily to measured adhesion forces.     

Macroscopic,Hierarchical, Two-Dimensional Self-Assembly

By tailoring capillary interactions at a fluid–fluid interface, a hierarchical two-dimensional self-assembly of hexagonal millimeter-sized poly(dimethylsiloxane) plates has been demonstrated (see picture). The strength and direction of capillary forces between plates was controlled by patterning of the surfaces of the plates to be hydophobic or hydrophilic. The thick lines indicate hydrophobic faces whose mutual attraction forms the basis of capillarity.     

Two-dimensional colloid crystals obtained by coupling of flow and confinement

This Letter describes the generation of 2D colloidal lattices in microchannels by coupling the laminar flow of dispersions of spherical colloids and geometrical confinement. We describe a nonequilibrium, convective, mechanism leading to formation of ordered 2D structures of both closed-packed hexagonal and non-closed-packed rhombic symmetries. The number and types of possible lattices is determined by the ratio of the width of the channel to the diameter of the particle. The structures tend to return to a regular lattice after a defect is introduced; that is, for example, they tend to self-repair disorder induced by particle polydispersity, contaminants, and flow instabilities. The stability of different lattices is analyzed numerically for particles with different polydispersity.     

Nonlinear dynamics of a flow-focusing bubble generator: an inverted dripping faucet

We describe the rich dynamic behavior--including period-doubling and period-halving bifurcations, intermittency, and chaos--observed in the breakup of an inviscid fluid in a coflowing, viscous liquid, both confined in a microfabricated flow-focusing geometry. Experimental observations support inertia-dominated dynamics of the interface, and suggest the possible similarity to the dynamics of a topologically inverted counterpart of this system, that is, a dripping faucet.