Showing papers by "George M. Whitesides published in 2007"

Patterned Paper as a Platform for Inexpensive, Low‐Volume, Portable Bioassays

Abstract: This communication describes a simple method for patterning paper to create well-defined, millimeter-sized channels, comprising hydrophilic paper bounded by hydrophobic polymer. We believe that this type of patterned paper will become the basis for low-cost, portable, and technically simple multiplexed bioassays. We demonstrate this capability by the simultaneous detection of glucose and protein in 5 μL of urine. The assay system is small, disposable, easy to use (and carry), and requires no external equipment, reagents, or power sources. We believe this kind of system is attractive for uses in less-industrialized countries, in the field, or as an inexpensive alternative to more advanced technologies already used in clinical settings.[1-4] The analysis of biological fluids is necessary for monitoring the health of populations,[2] but these measurements are difficult to implement in remote regions such as those found in less-industrialized countries, in emergency situations, or in home health-care settings.[3] Conventional laboratory instruments provide quantitative measurements of biological samples, but they are unsuitable for these situations since they are large, expensive, and require trained personnel and considerable volumes of biological samples.[2] Other bioassay platforms provide alternatives to more expensive instruments,[5-7] but the need remains for a platform that uses small volumes of sample and that is sufficiently inexpensive to be used widely for measuring samples from large populations. We believe that paper may serve as a particularly convenient platform for running bioassays in the remote situations locations. As a prototype for a mthod we believe to be particularly promosing, we patterned photoresist onto chromatography paper to form defined areas of hydrophilic paper separated by hydrophobic lines or “walls”; these patterns provide spatial control of biological fluids and enable fluid transport, without pumping, due to capillary action in the millimeter-sized channels produced. This method for patterning paper makes it possible to run multiple diagnostic assays on one strip of paper, while still using only small volumes of a single sample. In a fully developed technology, patterned photoresist would be replaced by an appropriate printing technology, but patterning paper with photoresist is: i) convenient for prototyping these devices, and ii) a useful new micropatterning technology in its own right. We patterned chromatography paper with SU-8 2010 photoresist as shown in Figure 1a and as described below: we soaked a 7.5-cm diameter piece of chromatography paper in 2 mL of SU-8 2010 for 30 s, spun it at 2000 rpm for 30 s, and then baked it at 95 °C for 5 min to remove the cyclopentanone in the SU-8 formula. We then exposed the photoresist and paper to 405 nm UV light (50 mW/cm2) for 10 s through a photo-mask (CAD/Art Services, Inc.) that was aligned using a mask aligner (OL-2 Mask Aligner, AB-M, Inc). After exposure, we baked the paper a second time at 95 °C for 5 min to cross-link the exposed portions of the resist. The unpolymerized photoresist was removed by soaking the paper in propylene glycol monomethyl ether acetate (PGMEA) (5 min), and by washing the pattern with propan-2-ol (3 × 10 mL). The paper was more hydrophobic after it was patterned, presumably due to residual resist bound to the paper, so we exposed the entire surface to an oxygen plasma for 10 s at 600 millitorr (SPI Plasma-Prep II, Structure Probe, Inc) to increase the hydrophilicity of the paper (Figures 2a and 2b). Figure 1 Chromatography paper patterned with photoresist. The darker lines are cured photoresist; the lighter areas are unexposed paper. (a) Patterned paper after absorbing 5 μL of Waterman red ink by capillary action. The central channel absorbs the sample ... Figure 2 Assays contaminated with (a) dirt, (b) plant pollen, and (c) graphite powder. The pictures were taken before and after running an artificial urine solution that contained 550 mM glucose and 75 μM BSA. The particulates do not move up the channels ... The patterned paper can be derivatized for biological assays by adding appropriate reagents to the test areas (Figures 1b and ​and2b).2b). In this communication, we demonstrate the method by detecting glucose and protein,[8] but the surface should be suitable for measuring many other analytes as well.[7] The glucose assay is based on the enzymatic oxidation of iodide to iodine,[9] where a color change from clear to brown is associated with the presence of glucose.[10] The protein assay is based on the color change of tetrabromophenol blue (TBPB) when it ionizes and binds to proteins;[11] a positive result in this case is indicated by a color change from yellow to blue. For the glucose assay, we spotted 0.3 μL of a 0.6 M solution of potassium iodide, followed by 0.3 μL of a 1:5 horseradish peroxidase/glucose oxidase solution (15 units of protein per mL of solution). For the protein assay, we spotted 0.3 μL of a 250-mM citrate buffer (pH 1.8) in a well separate from the glucose assay, and then layered 0.3 μL of a 3.3 mM solution of tetrabromophenol blue (TBPB) in 95% ethanol over the citrate buffer. The spotted reagents were allowed to air dry at room temperature. This pre-loaded paper gave consistent results for the protein assay regardless of storage temperature and time (when stored for 15 d both at 0 °C and at 23 °C, wrapped in aluminum foil). The glucose assay was sensitive to storage conditions, and showed decreased signal for assays run 24 h after spotting the reagents (when stored at 23 °C); when stored at 0 °C, however, the glucose assay was as sensitive after day 15 as it was on day 1. We measured artificial samples of glucose and protein in clinically relevant ranges (2.5-50 mM for glucose and 0.38-7.5 μM for bovine serum albumin (BSA))[12, 13] by dipping the bottom of each test strip in 5 μL of a pre-made test solution (Figure 2d). The fluid filled the entire pattern within ca. one minute, but the assays required 10-11 min for the paper to dry and for the color to fully develop.[14] In all cases, we observed color changes corresponding roughly in intensity to the amount of glucose and protein in the test samples, where the lowest concentrations define the lower limits to which these assays can be used (Figure 2e). For comparison, commercially-available dipsticks detect glucose at concentrations as low as 5 mM[7, 9] and protein as low as 0.75 μM;[6, 15] these limits indicate that these paper-based assays are comparable in sensitivity to commercial dipstick assays. Our assay format also allows for the measurement of multiple analytes. This paper-based assay is suitable for measuring multiple samples in parallel and in a relatively short period of time. For example, in one trial, one researcher was able to run 20 different samples (all with 550 mM glucose and 75 μM BSA) within 7.5 min (followed by another 10.5 min for the color to fully develop). An 18-min assay of this type—one capable of measuring two analytes in 20 different sample—may be efficient enough to use in high-throughput screens of larger sample pools. In the field, samples will not be measured under sterile conditions, and dust and dirt may contaminate the assays. The combination of paper and capillary action provides a mechanism for separating particulates from a biological fluid. As a demonstration, we purposely contaminated the artificial urine samples with quantities of dirt, plant pollen, and graphite powder at levels higher than we might expect to see in the samples in the field. These particulates do not move up the channels under the action of capillary wicking, and do not interfere with the assay (Figure 3). Paper strips have been used in biomedical assays for decades because they offer an inexpensive platform for colorimetric chemical testing.[1] Patterned paper has characteristics that lead to miniaturized assays that run by capillary action (e.g., without external pumping), with small volumes of fluids. These methods suggest a path for the development of simple, inexpensive, and portable diagnostic assays that may be useful in remote settings, and in particular, in less-industrialized countries where simple assays are becoming increasingly important for detecting disease and monitoring health,[16, 17], for environmental monitoring, in veterinary and agricultural practice and for other applications.

Microfabrication meets microbiology

Abstract: This Review summarizes methods for constructing systems and structures at micron or submicron scales that have applications in microbiology. These tools make it possible to manipulate individual cells and their immediate extracellular environments and have the capability to transform the study of microbial physiology and behaviour. Because of their simplicity, low cost and use in microfabrication, we focus on the application of soft lithographic techniques to the study of microorganisms, and describe several key areas in microbiology in which the development of new microfabricated materials and tools can have a crucial role.

Muscular Thin Films for Building Actuators and Powering Devices

Abstract: We demonstrate the assembly of biohybrid materials from engineered tissues and synthetic polymer thin films. The constructs were built by culturing neonatal rat ventricular cardiomyocytes on polydimethylsiloxane thin films micropatterned with extracellular matrix proteins to promote spatially ordered, two-dimensional myogenesis. The constructs, termed muscular thin films, adopted functional, three-dimensional conformations when released from a thermally sensitive polymer substrate and were designed to perform biomimetic tasks by varying tissue architecture, thin-film shape, and electrical-pacing protocol. These centimeter-scale constructs perform functions as diverse as gripping, pumping, walking, and swimming with fine spatial and temporal control and generating specific forces as high as 4 millinewtons per square millimeter.

The pressure drop along rectangular microchannels containing bubbles.

Abstract: This paper derives the difference in pressure between the beginning and the end of a rectangular microchannel through which a flowing liquid (water, with or without surfactant, and mixtures of water and glycerol) carries bubbles that contact all four walls of the channel. It uses an indirect method to derive the pressure in the channel. The pressure drop depends predominantly on the number of bubbles in the channel at both low and high concentrations of surfactant. At intermediate concentrations of surfactant, if the channel contains bubbles (of the same or different lengths), the total, aggregated length of the bubbles in the channel is the dominant contributor to the pressure drop. The difference between these two cases stems from increased flow of liquid through the “gutters”—the regions of the system bounded by the curved body of the bubble and the corners of the channel—in the presence of intermediate concentrations of surfactant. This paper presents a systematic and quantitative investigation of the influence of surfactants on the flow of fluids in microchannels containing bubbles. It derives the contributions to the overall pressure drop from three regions of the channel: (i) the slugs of liquid between the bubbles (and separated from the bubbles), in which liquid flows as though no bubbles were present; (ii) the gutters along the corners of the microchannels; and (iii) the curved caps at the ends of the bubble.

Dependence of effective molarity on linker length for an intramolecular protein-ligand system.

Abstract: This paper reports dissociation constants and “effective molarities” (Meff) for the intramolecular binding of a ligand covalently attached to the surface of a protein by oligo(ethylene glycol) (EGn) linkers of different lengths (n = 0, 2, 5, 10, and 20) and compares these experimental values with theoretical estimates from polymer theory. As expected, the value of Meff is lowest when the linker is too short (n = 0) to allow the ligand to bind noncovalently at the active site of the protein without strain, is highest when the linker is the optimal length (n = 2) to allow such binding to occur, and decreases monotonically as the length increases past this optimal value (but only by a factor of ∼8 from n = 2 to n = 20). These experimental results are not compatible with a model in which the single bonds of the linker are completely restricted when the ligand has bound noncovalently to the active site of the protein, but they are quantitatively compatible with a model that treats the linker as a random-coil p...

Microsolidics: Fabrication of Three‐Dimensional Metallic Microstructures in Poly(dimethylsiloxane)

Abstract: This Communication describes a method of fabricating complex metallic microstructures in 3D by injecting liquid solder into microfluidic channels, and allowing the solder to cool and solidify; after fabrication, the metallic structures can be flexed, bent, or twisted This method of fabrication—which we call microsolidics—takes advantage of the techniques that were developed for fabricating microfluidic channels in poly(dimethylsiloxane) (PDMS) in 2D and 3D, uses surface chemistry to control the interfacial free energy of the metal– PDMS interface, and uses techniques based on microfluidics, but ultimately generates solid metal structures This approach makes it possible to build flexible electronic circuits or connections between circuits, complex embedded or freestanding 3D metal microstructures, 3D electronic components, and hybrid electronic–microfluidic devices There are several techniques for making metal microstructures in 3D Electroplating and electroless deposition are routinely used to construct microstructures with metallic layers several nanometers to several microns thick in 2D or 3D [1–11] To generate solid replicas of 3D objects, several groups have developed a technique, referred to as “microcasting”, to form metals in order to fabricate microparts (eg, posts and gears) with features as small as 10 lm and aspect ratios as high as 10 from steel, zirconia, and alumina [12,13] Techniques based on LIGA (Lithographie, Galvanoformung, und Abformung) produce even more complicated metallic objects by depositing a metal onto a molded polymer template that is subsequently removed to yield an open structure (such as a honeycomb arrangement of cells) [14,15] In principle, these approaches can be used to pattern metals of any thickness to produce features with an aspect ratio that is larger than that produced using electroplating

The force acting on a superparamagnetic bead due to an applied magnetic field.

Abstract: This paper describes a model of the motion of superparamagnetic beads in a microfluidic channel under the influence of a weak magnetic field produced by an electric current passing through a coplanar metal wire. The model based on the conventional expression for the magnetic force experienced by a superparamagnetic bead (suspended in a biologically relevant medium) and the parameters provided by the manufacturer failed to match the experimental data. To fit the data to the model, it was necessary to modify the conventional expression for the force to account for the non-zero initial magnetization of the beads, and to use the initial magnetization and the magnetic susceptibility of the beads as adjustable parameters. The best-fit value of susceptibility deviated significantly from the value provided by the manufacturer, but was in good agreement with the value computed using the magnetization curves measured independently for the beads from the same vial as those used in the experiment. The results of this study will be useful to researchers who need an accurate prediction of the behavior of superparamagnetic beads in aqueous suspensions under the influence of weak magnetic fields. The derivation of the force on a magnetic bead due to a magnetic field also identifies the correct treatment to use for this interaction, and resolves discrepancies present throughout the literature.

A microfabricated array of clamps for immobilizing and imaging C. elegans

Abstract: This paper describes the fabrication of a microfluidic device for rapid immobilization of large numbers of live C. elegans for performing morphological analysis, microsurgery, and fluorescence imaging in a high-throughput manner. The device consists of two principal elements: (i) an array of 128 wedge-shaped microchannels, or clamps, which physically immobilize worms, and (ii) a branching network of distribution channels, which deliver worms to the array. The flow of liquid through the device (driven by a constant pressure difference between the inlet and the outlet) automatically distributes individual worms into each clamp. It was possible to immobilize more than 100 worms in less than 15 min. The immobilization process was not damaging to the worms: following removal from the array of clamps, worms lived typical lifespans and reproduced normally. The ability to monitor large numbers of immobilized worms easily and in parallel will enable researchers to investigate physiology and behavior in large populations of C. elegans.

Coding/Decoding and Reversibility of Droplet Trains in Microfluidic Networks

Abstract: Droplets of one liquid suspended in a second, immiscible liquid move through a microfluidic device in which a channel splits into two branches that reconnect downstream. The droplets choose a path based on the number of droplets that occupy each branch. The interaction among droplets in the channels results in complex sequences of path selection. The linearity of the flow through the microchannels, however, ensures that the behavior of the system can be reversed. This reversibility makes it possible to encrypt and decrypt signals coded in the intervals between droplets. The encoding/decoding device is a functional microfluidic system that requires droplets to navigate a network in a precise manner without the use of valves, switches, or other means of external control.

Si/SiO2-Templated Formation of Ultraflat Metal Surfaces on Glass, Polymer, and Solder Supports: Their Use as Substrates for Self-Assembled Monolayers

Abstract: This paper describes the use of several methods of template stripping (TS) to produce ultraflat films of silver, gold, palladium, and platinum on both rigid and polymeric mechanical supports: a composite of glass and ultraviolet (UV)-curable adhesive (optical adhesive, OA), solder, a composite of poly(dimethyl siloxane) (PDMS) and OA, and bare OA. Silicon supporting its native oxide layer (Si/SiO2) serves as a template for both mechanical template stripping (mTS), in which the metal film is mechanically cleaved from the template, and chemical template stripping (cTS), in which the film−template composite is immersed in a solution of thiols, and the formation of the SAM on the metal film causes the film to separate from the template. Films formed on all supports have lower root-mean-square (rms) roughness (as measured by atomic force microscopy, AFM) than films used as-deposited (AS-DEP) by electron-beam evaporation. Monolayers of n-dodecanethiolate formed by the mTS and cTS methods are effectively indist...

Influence of Defects on the Electrical Characteristics of Mercury-Drop Junctions: Self-Assembled Monolayers of n-Alkanethiolates on Rough and Smooth Silver

Abstract: This paper compares the structural and electrical characteristics of self-assembled monolayers (SAMs) of n-alkanethiolates, SCn (n = 10, 12, 14), on two types of silver substrates: one used as-deposited (AS-DEP) by an electron-beam evaporator, and one prepared using the method of template-stripping Atomic force microscopy showed that the template-stripped (TS) silver surfaces were smoother and had larger grains than the AS-DEP surfaces, and reflectance−absorbance infrared spectroscopy showed that SAMs formed on TS substrates were more crystalline than SAMs formed on AS-DEP substrates The range of current densities, J (A/cm2), measured through mercury-drop junctions incorporating a given SAM on AS-DEP silver was, on average, several orders of magnitude larger than the range of J measured through the same SAM on TS silver, and the AS-DEP junctions failed, on average, 35 times more often within five current density−voltage (J−V) scans than did TS junctions (depending on the length of the alkyl chains of

Don't Forget Long-Term Fundamental Research in Energy

Abstract: Achieving a fundamental understanding of the phenomena that will underpin both global stewardship and future technologies in energy calls for a thoughtful balance between large-scale immediate solutions using existing technology and the fundamental research needed to provide better solutions in the 50-year period.

Ionic electrets: electrostatic charging of surfaces by transferring mobile ions upon contact.

Abstract: This paper describes the fabrication and characterization of ionic electretsmaterials that bear a long-lived electrostatic charge because of an imbalance between the number of cationic and anionic charges in the material. Crosslinked polystyrene microspheres that contain covalently bound ions and mobile counterions transfer some of their mobile ions in air, in the absence of bulk liquid, to another material upon contact. According to the ion-transfer model of contact electrification, this selective transfer of mobile ions yields microspheres that have a net electrostatic charge. A tool that operates on the principle of electrostatic induction measures the charge on individual microspheres (50−450 μm in diameter). Microspheres with a variety of covalently bound ionic functional groups (tetraalkylammonium, alkyltriphenylphosphonium, alkylsulfonate, and arylsulfonate) acquire charges consistent with this ion-transfer mechanism. The charge on a microsphere is proportional to its surface area (ca. 1 elementary...

Fabrication of large-area patterned nanostructures for optical applications by nanoskiving.

Abstract: Cost-effective and convenient methods for fabrication of patterned metallic nanostructures over the large (mm2) areas required for applications in photonics are much needed. In this paper, we demonstrate the fabrication of arrays of closed and open, loop-shaped nanostructures by a technique (nanoskiving) that combines thin-film deposition by metal evaporation with thin-film sectioning. These arrays of metallic structures serve as frequency-selective surfaces at mid-infrared wavelengths. Experiments with structures prepared using this technique demonstrate that a closed-looped structure has a single dominant resonance regardless of the polarization of the incident light, while open structures have resonances that are anisotropic with respect to the polarization of the electric field. Finite-difference time-domain (FDTD) simulations reproduce the scattering spectra of these frequency-selective surfaces, provide an explanation of the wavelength of the experimentally observed resonances, and rationalize their...

Synthesis of composite emulsions and complex foams with the use of microfluidic flow-focusing devices.

Abstract: A method is described for the formation of stable, composite aqueous emulsions of 1) combinations of distinct families of bubbles of nitrogen, 2) combinations of distinct families of droplets of an organic fluid (either perfluoro(methyl)decalin or hexadecane), and 3) combinations of bubbles and droplets. A system of two or three microfluidic flow-focusing units is coupled to a single outlet channel. The composite emulsions can be precisely tuned, both in their composition and in the number fraction of components--either bubbles or droplets--of different types. The use of microfluidic technology, with closely coupled flow-focusing units, guarantees that the emulsions are mixed locally at a controlled local stoichiometry. The emulsions self-assemble in a nonequilibrium process to form a wide variety of highly organized periodic lattices.

Density-Based Diamagnetic Separation: Devices for Detecting Binding Events and for Collecting Unlabeled Diamagnetic Particles in Paramagnetic Solutions

Abstract: This paper describes the fabrication of a fluidic device for detecting and separating diamagnetic materials that differ in density. The basis for the separation is the balance of the magnetic and gravitational forces on diamagnetic materials suspended in a paramagnetic medium. The paper demonstrates two applications of separations involving particles suspended in static fluids for detecting the following: (i) the binding of streptavidin to solid-supported biotin and (ii) the binding of citrate-capped gold nanoparticles to amine-modified polystyrene spheres. The paper also demonstrates a microfluidic device in which polystyrene particles that differ in their content of CH2Cl groups are continuously separated and collected in a flowing stream of an aqueous solution of GdCl3. The procedures for separation and detection described in this paper require only gadolinium salts, two NdFeB magnets, and simple microfluidic devices fabricated from poly(dimethylsiloxane). This device requires no power, has no moving ...

Electrostatic Self-Assembly of Polystyrene Microspheres by Using Chemically Directed Contact Electrification

Abstract: Herein we describe a process—based on contact electrification and electrostatic interactions—that directs the selfassembly of chemically modified polystyrene microspheres to form three-dimensional microstructures. When two solid surfaces are brought into contact and separated, charge is often transferred from one surface to the other in a process known as contact electrification. 2] We can predictably and rationally control the contact electrification of polystyrene microspheres, and use the resulting charged materials for electrostatic self-assembly. We control the contact electrification of these microspheres by introducing immobilized ions and mobile counterions: the choice of these ions determines the electrostatic charges that these beads acquire through contact before and during the assembly process. Oppositely charged microspheres assemble into uniform spherical microstructures under the influence of electrostatic forces. Sequential steps of self-assembly can create multilayered microstructures. There are many examples of electrostatic self-assembly of charged ions, polyelectrolytes, and colloids in solution. Xerography, an example of dry electrostatic self-assembly, uses corona discharge from a high-voltage electrode to create a charge on the imaging drum, and contact electrification to create an opposite charge on the toner particles. Contact electrification can also direct the self-assembly of millimetersized spheres into ordered two-dimensional lattices. (That process used the inherent differences in contact electrification of various polymers, in contrast to the rational, chemically directed contact electrification we describe herein.) Patterns of charge, created by electron-beam writing, an atomic force microscopy (AFM) tip, or electrical microcontact printing on a dielectric surface, can guide the self-assembly of microor nanoparticles with sub-100 nm lateral resolution. Although contact electrification is a familiar phenomenon, the detailed mechanisms of contact electrification are not known, and it is likely that different mechanisms may be involved depending on the specific materials and environmental conditions. There is one class of materials that exhibits predictable contact electrification and for which Diaz and coworkers have proposed a plausible mechanism of chargetransfer: the contact charging of ionomers (polymers with covalently bound ionic functional groups) is believed to result from the transfer of mobile ions from the ionomer to another material (Figure 1).

Elastomeric mask and use in fabrication of devices

Abstract: An elastomeric mask is provided that allows deposition of a variety of materials through mask openings. The mask seals effectively against substrate surfaces, allowing simple deposition from fluid phase, gas phase, and the like or removal of material using gaseous or liquid etchants. The mask then can be simply peeled from the surface of the substrate leaving the patterned material behind. Multi-layered mask techniques are described in which openings in an upper mask allow selected openings of a lower mask to remain un-shielded, while other openings of the lower mask are shielded. A first deposition step, following by re-orientation of the upper mask to expose a different set of lower mask openings, allows selective deposition of different materials in different openings of the lower mask. Pixelated organic electroluminescent devices are provided via the described technique.

Fabrication of Complex Metallic Nanostructures by Nanoskiving

Abstract: This paper describes the use of nanoskiving to fabricate complex metallic nanostructures by sectioning polymer slabs containing small, embedded metal structures. This method begins with the deposition of thin metallic films on an epoxy substrate by e-beam evaporation or sputtering. After embedding the thin metallic film in an epoxy matrix, sectioning (in a plane perpendicular or parallel to the metal film) with an ultramicrotome generates sections (which can be as thin as 50 nm) of epoxy containing metallic nanostructures. The cross-sectional dimensions of the metal wires embedded in the resulting thin epoxy sections are controlled by the thickness of the evaporated metal film (which can be as small as 20 nm) and the thickness of the sections cut by the ultramicrotome; this work uses a standard 45° diamond knife and routinely generates slabs 50 nm thick. The embedded nanostructures can be transferred to, and positioned on, planar or curved substrates by manipulating the thin polymer film. Removal of the e...

Pumping fluids in microfluidic systems using the elastic deformation of poly(dimethylsiloxane).

Abstract: This paper demonstrates a methodology for storing and pumping fluids that provide a useful capability for microfluidic devices. It uses microfluidic screw valves to isolate fluids in poly(dimethylsiloxane) (PDMS) microcompartments, in which the pressure of the liquid is stored in the elastic deformation of the walls and ceiling of the compartments. Fluids can be stored under pressure in these structures for months. When the valves are opened, the walls and ceiling push the fluid out of the compartments into microfluidic channels. The system has five useful characteristics: (i) it is made using soft lithographic techniques; (ii) it allows multiple reagents to be preloaded in devices and stored under pressure without any additional user intervention; (iii) it makes it possible to meter out fluids in devices, and to control rates of flow of fluids; (iv) it prevents the user from exposure to potentially toxic reagents; and (v) it is hand-operated and does not require additional equipment or resources.

The study of charge transport through organic thin films: mechanism, tools and applications.

Abstract: In this paper, we discuss the current state of organic and molecular-scale electronics, some experimental methods used to characterize charge transport through molecular junctions and some theoretical models (superexchange and barrier tunnelling models) used to explain experimental results. Junctions incorporating self-assembled monolayers of organic molecules—and, in particular, junctions with mercury-drop electrodes—are described in detail, as are the issues of irreproducibility associated with such junctions (due, in part, to defects at the metal–molecule interface).

Lateral flow and flow-through bioassay based on patterned porous media, methods of making same, and methods of using same

Abstract: Embodiments of the invention provide lateral flow and flow-through bioassay devices based on patterned porous media, methods of making same, and methods of using same. Under one aspect, an assay device includes a porous, hydrophilic medium; a fluid impervious barrier comprising polymerized photoresist, the barrier substantially permeating the thickness of the porous, hydrophilic medium and defining a boundary of an assay region within the porous, hydrophilic medium; and an assay reagent in the assay region.

Thermodynamic parameters for the association of fluorinated benzenesulfonamides with bovine carbonic anhydrase II.

Abstract: This paper describes a calori- metric study of the association of a series of seven fluorinated benzenesul- fonamide ligands (C6HnF5� nSO2NH2) with bovine carbonic anhydrase II (BCA). Quantitative structure-activity relationships between the free energy, enthalpy, and entropy of binding and pKa and log P of the ligands allowed the evaluation of the thermodynamic parameters in terms of the two inde- pendent effects of fluorination on the ligand: its electrostatic potential and its hydrophobicity. The parameters were partitioned to the three different struc- tural interactions between the ligand and BCA: the Zn II cofactor-sulfon- A bond ( � 65 % of the free energy of binding), the hydrogen bonds be- tween the ligand and BCA ( � 10 %), and the contacts between the phenyl ring of the ligand and BCA ( � 25 %). Calorimetry revealed that all of the li- gands studied bind in a 1:1 stoichiome- try with BCA; this result was con- firmed by 19 F NMR spectroscopy and X-ray crystallography (for complexes with human carbonic anhydrase II).

A Synthetic Trivalent Hapten that Aggregates Anti-2,4-DNP IgG into Bicyclic Trimers

Abstract: This paper describes the synthesis of the trivalent hapten molecule 1, containing three 2,4-dinitrophenyl (2,4-DNP) groups, and the use of this molecule to aggregate three molecules of anti-2,4-DNP IgG into a complex with 3:2 stoichiometry (IgG312). The equilibrium product IgG312 was generated in ∼90% yield upon mixing IgG and 1; during incubation, thermodynamically unstable, high-molecular-weight aggregates (>104 nm in diameter) form first and convert subsequently to IgG312. The thermodynamics and the kinetics of the formation of aggregates were studied using size-exclusion high-performance liquid chromatography (SE-HPLC), dynamic light scattering (DLS), and analytical ultracentrifugation (AUC). An analytical model based on multiple species in equilibrium was developed and used to interpret the SE-HPLC data. The aggregate IgG312 was more stable thermodynamically and kinetically than monomeric aggregates of this IgG with monomeric derivatives of 2,4-DNP; this stability suggests potential applications of t...

Fabrication and Manipulation of Ionotropic Hydrogels Crosslinked by Paramagnetic Ions.

Abstract: This article describes the fabrication and manipulation of millimeter-scale spheres fabricated from ionotropic hydrogels that are cross-linked with paramagnetic metal ions (e.g., Ho 3+ ). These ionotropic hydrogels experience a force in a magnetic field gradient that correlates with the concentration of the paramagnetic cations cross-linking the polymer. In an externally applied magnetic field, the paramagnetic hydrogel spheres assemble into ordered arrays or confined geometrical structures in the regions of highest magnetic field. These spheres can be separated from heterogeneous mixtures of diamagnetic materials using a simple bar magnet. Two applications using these recoverable hydrogel spheres were demonstrated: (i) When prepared with embedded indicator dyes bound to paper, the spheres were used as colorimetric sensors for pH. (ii) When prepared with embedded activated carbon powder, they were used to remove organic materials from aqueous solutions.

Patterning micron-sized features in a cross-linked poly(acrylic acid) film by a wet etching process

Abstract: This paper describes a photolithographic method to create sub-micron-scale patterns of cation-cross-linked poly(acrylic acid) (CCL-PAA). PAA can be cross-linked with a wide range of metal cations—including, but not limited to, Ag+, Ca2+, Pd2+, Al3+, La3+, and Ti4+. Upon patterning a positive photoresist (diazonaphthoquinone-novolac resin) on a film of CCL-PAA, the exposed regions of CCL-PAA were etched by either an aqueous NaOH or EDTA solution. The initial cross-linking cation could be exchanged for a second cation that could not be patterned photolithographically. We used these patterned films of CCL-PAA i) to host and template the reduction of metallic cations to metallic nanoparticles, and ii) to fabricate porous, low-k dielectric substrates.

Engineered cell growth on polymeric films and biotechnological applications there of

Abstract: A free-standing thin film is fabricated from a structure comprising a base layer coated with a sacrificial polymer layer, which is in turn coated with a flexible polymer layer. Cells are then seeded onto the flexible polymer layer and cultured to form a tissue. The flexible polymer layer is then released from the base layer to produce a free-standing thin film comprising the tissue on the flexible polymer layer. In one embodiment, the cells are myocytes, which can be actuated to propel or displace the free-standing film. In another embodiment, the free-standing film is used to treat injured human tissue.

Terahertz plasmonic composites.

Abstract: The dielectric response of a polymer matrix composite can be substantially modified and tuned within a broad frequency band by integrating within the material an artificial plasmon medium composed of periodically distributed, very thin, electrically conducting wires. In the microwave regime, such plasmon/polymer composites have been studied analytically, computationally, and experimentally. This work reports the design, fabrication, and characterization of similar composites for operation at terahertz frequencies. Such composites require significant reduction in the thickness and spacing of the wires. We used numerical modeling to design artificial effective plasmonic media with turn-on frequencies in the terahertz range. Prototype samples were produced by lithographically embedding very thin gold strips into a PDMS [poly(dimethylsiloxane)] matrix. These samples were characterized with a Fourier-transform infrared interferometer using the frequency-dependent transmission and Kramers-Kronig relations to determine the electromagnetic properties. We report the characterization results for a sample, demonstrating excellent agreement between theory, computer design, and experiment. To our knowledge this is the first demonstration of the possibility of creating composites with tuned dielectric response at terahertz frequencies.