Showing papers by "George M. Whitesides published in 2010"

Diagnostics for the Developing World: Microfluidic Paper-Based Analytical Devices

Abstract: Microfluidic paper-based analytical devices (μPADs) are a new class of point-of-care diagnostic devices that are inexpensive, easy to use, and designed specifically for use in developing countries. (To listen to a podcast about this feature, please go to the Analytical Chemistry multimedia page at pubs.acs.org/page/ancham/audio/index.html.)

Soft lithography for micro- and nanoscale patterning

Abstract: This protocol provides an introduction to soft lithography--a collection of techniques based on printing, molding and embossing with an elastomeric stamp. Soft lithography provides access to three-dimensional and curved structures, tolerates a wide variety of materials, generates well-defined and controllable surface chemistries, and is generally compatible with biological applications. It is also low in cost, experimentally convenient and has emerged as a technology useful for a number of applications that include cell biology, microfluidics, lab-on-a-chip, microelectromechanical systems and flexible electronics/photonics. As examples, here we focus on three of the commonly used soft lithographic techniques: (i) microcontact printing of alkanethiols and proteins on gold-coated and glass substrates; (ii) replica molding for fabrication of microfluidic devices in poly(dimethyl siloxane), and of nanostructures in polyurethane or epoxy; and (iii) solvent-assisted micromolding of nanostructures in poly(methyl methacrylate).

Electrochemical sensing in paper-based microfluidic devices

Abstract: This paper describes the fabrication and the performance of microfluidic paper-based electrochemical sensing devices (we call the microfluidic paper-based electrochemical devices, µPEDs). The µPEDs comprise paper-based microfluidic channels patterned by photolithography or wax printing, and electrodes screen-printed from conducting inks (e.g., carbon or Ag/AgCl). We demonstrated that the µPEDs are capable of quantifying the concentrations of various analytes (e.g., heavy-metal ions and glucose) in aqueous solutions. This low-cost analytical device should be useful for applications in public health, environmental monitoring, and the developing world.

Foldable Printed Circuit Boards on Paper Substrates

Abstract: This paper describes several low-cost methods for fabricating flexible electronic circuits on paper. The circuits comprise i) metallic wires (e.g., tin or zinc) that are deposited on the substrate by evaporation, sputtering, or airbrushing, and ii) discrete surface-mountable electronic components that are fastened with conductive adhesive directly to the wires. These electronic circuits—like conventional printed circuit boards—can be produced with electronic components that connect on both sides of the substrate. Unlike printed circuit boards made from fiberglass, ceramics, or polyimides, however, paper can be folded and creased (repeatedly), shaped to form three-dimensional structures, trimmed using scissors, used to wick fluids (e.g., for microfluidic applications) and disposed of by incineration. Paper-based electronic circuits are thin and lightweight; they should be useful for applications in consumer electronics and packaging, for disposable systems for uses in the military and homeland security, for applications in medical sensing or low-cost portable diagnostics, for paper-based microelectromechanical systems, and for applications involving textiles.

Paper-Based ELISA

Abstract: This paper describes enzyme-linked immunosorbent assays (ELISA) performed in a 96-microzone plate fabricated in paper (paper-based ELISA, or P-ELISA). ELISA is widely used in biochemical analyses; these assays are typically carried out in microtiter plates or small vials. 2] ELISA combines the specificity of antibodies with high-turnover catalysis by enzymes to provide specificity and sensitivity. We have recently described a 96-microzone paper plate— fabricated by patterning hydrophobic polymer in hydrophilic paper—as a platform for biochemical analysis. Although microfluidic paper-based analytical devices (mPADs) were designed primarily to provide analytical capability at low cost in developing countries, we expect that they will also be useful in applications such as point-of-care clinical analysis, military and humanitarian aid field operations, and others where high throughput, low volumes of sample, low cost, and robustness are important. These devices have so far been prototyped using analyses of simple analytes: glucose, total protein, and certain enzymes. P-ELISA combines the sensitivity and specificity of ELISA with the convenience, low cost and ease-of-use of paper-based platforms; P-ELISA (at it current state of development) is faster and less expensive than conventional ELISA, but somewhat less sensitive. Porous membranes, including nitrocellulose and filter paper, have been used for decades in dot-immunobinding assays (DIA). Though DIAs are the simplest form of immunoassays on paper, they typically require one piece of nitrocellulose for each assay; the pieces of nitrocellulose have to be processed individually in Petri dishes, and the assays take several hours to complete. Quantitative DIAs have been reported, but DIAs are typically qualitative, and provide only “yes/no” results. Conventional ELISA, usually performed in 96-well plates (fabricated by injection molding in plastic), is quantitative and well-suited for highthroughput assays, but each assay requires large volumes (ca. 20–200 mL) of analyte and reagents, the time required for incubation and blocking steps are long ( 1 h per step, because the reagents must diffuse to the surface of the wells), and the results are usually quantified using a plate reader, typically a $20 000 instrument. Paper microzone plates for ELISA can have the same layout as plastic 96-well plates, but each test zone requires only about 3 mL of sample, and the results can be measured using a desktop scanner, typically a $100 instrument. In addition, an entire P-ELISA can be completed in less than one hour. The ease of fabrication of paper microzone plates also opens opportunities for a wide range of non-standard formats, and customized connections to carry reagents between zones. To evaluate the feasibility of P-ELISA, and the potential advantages and disadvantages of P-ELISA and 96-well-plate-based ELISA, we adapted a standard procedure to our format and then demonstrated an indirect P-ELISA using rabbit IgG as a model analyte. We also established that P-ELISA can be used to detect and quantify antibodies to the HIV-1 envelope antigen gp41 in human serum using an anti-human IgG antibody conjugated to alkaline phosphatase (ALP) to produce a colorimetric readout. We used a 96-microzone paper plate with an array (12 8) of circular test zones for running multiple P-ELISAs in parallel (Figure 1A); the Supporting Information describes the details. The array was designed to have the same layout and dimensions as a standard plastic 96-well plate, so that it would be compatible with existing microanalytical infrastructure (eightor twelve-channel pipettes and plate readers). Each test zone was 5 mm in diameter and required 3 mL of solution to fill (e.g., to wet completely with fluid); this design was a good compromise between convenience and conservation of reagents, as it reduced the amount of reagents and sample required for the assay but ensured accurate distribution of fluids when using a manual pipette. We also examined smaller test zones, with the smallest test zone requiring 0.5 mL of solution to fill (e.g., to wet completely). This size is similar to that required in a 384-well plate format. The top and bottom faces of the test zones in papermicrozone plates are open to atmosphere. The advantage of this configuration is that the zones can be washed by adding a washing buffer to the top of the zone while pressing the bottom of the zone against a piece of blotting paper. The washing buffer goes through the test zone vertically and into [*] Dr. C.-M. Cheng, Dr. A. W. Martinez, Dr. J. Gong, Dr. C. R. Mace, Prof. S. T. Phillips, Prof. E. Carrilho, K. A. Mirica, Prof. G. M. Whitesides Department of Chemistry and Chemical Biology Harvard University Cambridge, MA 02138 (USA) E-mail: gwhitesides@gmwgroup.harvard.edu Homepage: http://gmwgroup.harvard.edu

Integration of paper-based microfluidic devices with commercial electrochemical readers

Abstract: The combination of simple Electrochemical Micro-Paper-based Analytical Devices (EµPADs) with commercially available glucometers allows rapid, quantitative electrochemical analysis of a number of compounds relevant to human health (e.g., glucose, cholesterol, lactate, and alcohol) in blood or urine.

Stretchable Microfluidic Radiofrequency Antennas

Abstract: www.MaterialsViews.com C O M Stretchable Microfl uidic Radiofrequency Antennas M U N I By Masahiro Kubo , Xiaofeng Li , Choongik Kim , Michinao Hashimoto , Benjamin J. Wiley , Donhee Ham , and George M. Whitesides * C A IO N This paper describes a new method for fabricating stretchable radiofrequency antennas. The antennas consist of liquid metal (eutectic gallium indium alloy, EGaIn [ 1 , 2 ] ) enclosed in elastomeric microfl uidic channels. In particular, a microfl uidic structure made of two types of elastomers (polydimethylsiloxane (PDMS) and Ecofl ex (type 0030, Reynolds Advanced Materials)) with different stiffness has been developed to improve the stretchability and mechanical stability of the antennas. These antennas can be stretched up to a strain [defi ned as the percentage change in length or ( l – l 0 )/ l 0 ] of 120 %. This high stretchability allows the resonance frequencies of the antennas to be mechanically tuned over a wide range of frequencies. The antennas can also be repeatedly stretched, while retaining a high effi ciency (> 95 %) in radiation. “Stretchability” in electronics has the potential to open new opportunities, particularly for large-area devices and systems, and in systems that require the device to conform to a nonplanar surface, or to bend and stretch while in use. [ 3–5 ] Compared to “fl exible” electronics built on nonstretchable polymer or paper substrates, [ 6 , 7 ] stretchable electronics can cover almost arbitrarily curved surfaces and movable parts. Mechanical compliance may increase the comfort of the user for wearable electronics or implantable medical devices, and simplify the integration for a range of applications. [ 3–5 , 8 ] New approaches to stretchable electronics are now being developed. In a recent advance, Rogers et al. [ 4 , 5 ] described stretchable integrated circuits with elongation of up to 100 % using wavy, thin silicon ribbons on pre-stretched elastic substrates. Antennas offer new, attractive applications for stretchable electronics; these applications might include reconfi gurable antennas, [ 9 ] antennas for limited and nonplanar spaces, [ 10 ] and wearable sensors. Two methods are commonly used to build antennas for commercial applications. The most common method uses sheet-metal processing; in this method, a metal sheet is punched, bent, and welded into the desired structure. A second method uses chemical etching and plating to make small patterns of metal. This method can make fl exible antennas by patterning metal on a fl exible substrate. Neither

Programmable diagnostic devices made from paper and tape

Abstract: This paper describes three-dimensional microfluidic paper-based analytical devices (3-D µPADs) that can be programmed (postfabrication) by the user to generate multiple patterns of flow through them. These devices are programmed by pressing single-use ‘on’ buttons, using a stylus or a ballpoint pen. Pressing a button closes a small space (gap) between two vertically aligned microfluidic channels, and allows fluids to wick from one channel to the other. These devices are simple to fabricate, and are made entirely out of paper and double-sided adhesive tape. Programmable devices expand the capabilities of µPADs and provide a simple method for controlling the movement of fluids in paper-based channels. They are the conceptual equivalent of field-programmable gate arrays (FPGAs) widely used in electronics.

Thread as a Matrix for Biomedical Assays

Abstract: This paper describes the use of thread as a matrix for the fabrication of diagnostic assay systems. The kinds of thread used for this study are inexpensive, broadly available, and lightweight; some of them are already familiar materials in healthcare. Fluids wick along these threads by capillary action; no external power source is necessary for pumping. This paper demonstrates three designs for diagnostic assays that use different characteristics of the thread. The first two designs—the “woven array” and the “branching design”—take advantage of the ease with which thread can be woven on a loom to generate fluidic pathways that enable multiple assays to be performed in parallel. The third design—the “sewn array”—takes advantage of the ease with which thread can be sewn through a hydrophobic polymer sheet to incorporate assays into bandages, diapers and similar systems. These designs lead to microfluidic devices that may be useful in performing simple colorimetric assays that require qualitative results. We...

Lifespan-on-a-chip: microfluidic chambers for performing lifelong observation of C. elegans †

Abstract: This article describes the fabrication of a microfluidic device for the liquid culture of many individual nematode worms (Caenorhabditis elegans) in separate chambers. Each chamber houses a single worm from the fourth larval stage until death, and enables examination of a population of individual worms for their entire adult lifespans. Adjacent to the chambers, the device includes microfluidic worm clamps, which enable periodic, temporary immobilization of each worm. The device made it possible to track changes in body size and locomotion in individual worms throughout their lifespans. This ability to perform longitudinal measurements within the device enabled the identification of age-related phenotypic changes that correlate with lifespan in C. elegans.

Charge Transport and Rectification in Arrays of SAM-Based Tunneling Junctions

Abstract: This paper describes a method of fabrication that generates small arrays of tunneling junctions based on self-assembled monolayers (SAMs); these junctions have liquid-metal top-electrodes stabilized in microchannels and ultraflat (template-stripped) bottom-electrodes. The yield of junctions generated using this method is high (70−90%). The junctions examined incorporated SAMs of alkanethiolates having ferrocene termini (11-(ferrocenyl)-1-undecanethiol, SC11Fc); these junctions rectify currents with large rectification ratios (R), the majority of which fall within the range of 90−180. These values are larger than expected (theory predicts R ≤ 20) and are larger than previous experimental measurements. SAMs of n-alkanethiolates without the Fc groups (SCn−1CH3, with n = 12, 14, 16, or 18) do not rectify (R ranged from 1.0 to 5.0). These arrays enable the measurement of the electrical characteristics of the junctions as a function of chemical structure, voltage, and temperature over the range of 110−293 K, wi...

Mechanism of Rectification in Tunneling Junctions Based on Molecules with Asymmetric Potential Drops

Abstract: This paper proposes a mechanism for the rectification of current by self-assembled monolayers (SAMs) of alkanethiolates with Fc head groups (SC11Fc) in SAM-based tunneling junctions with ultra-flat Ag bottom electrodes and liquid metal (Ga2O3/EGaIn) top electrodes. A systematic physical-organic study based on statistically large numbers of data (N = 300−1000) reached the conclusion that only one energetically accessible molecular orbital (the HOMO of the Fc) is necessary to obtain large rectification ratios R ≈ 1.0 × 102 (R = |J(−V)|/|J(V)| at ±1 V). Values of R are log-normally distributed, with a log-standard deviation of 3.0. The HOMO level has to be positioned spatially asymmetrically inside the junctions (in these experiments, in contact with the Ga2O3/EGaIn top electrode, and separated from the Ag electrode by the SC11 moiety) and energetically below the Fermi levels of both electrodes to achieve rectification. The HOMO follows the potential of the Fermi level of the Ga2O3/EGaIn electrode; it overla...

Magnetic levitation in the analysis of foods and water.

Abstract: This paper describes a method and a sensor that use magnetic levitation (MagLev) to characterize samples of food and water on the basis of measurements of density. The sensor comprises two permanent NdFeB magnets positioned on top of each other in a configuration with like poles facing and a container filled with a solution of paramagnetic ions. Measurements of density are obtained by suspending a diamagnetic object in the container filled with the paramagnetic fluid, placing the container between the magnets, and measuring the vertical position of the suspended object. MagLev was used to estimate the salinity of water, to compare a variety of vegetable oils on the basis of the ratio of polyunsaturated fat to monounsaturated fat, to compare the contents of fat in milk, cheese, and peanut butter, and to determine the density of grains.

Thiol—disulfide interchange

Abstract: INTRODUCTION METHODS USED IN FOLLOWING THIOL-DISULFIDE INTERCHANGE A. Spectroscopic (UV, NMR) Assays B. Enzymatic Assays C. Assays Based on Chromatography MECHANISM A. Products B. Dependence on Solut ion pH, and on the pK" Values of Thiols C. Kinetics 1. Rate law 2. Br/nsted relat ion 3. Substituent effects a. Steric b. Acidity c. Charge d. Hydrogen bonding e. Reactions involving cyclic disulfides 4. Solvent effects 5. Gas-phase studies 6. Catalysis 7. Comparison with selenolate-diselenide interchange D. Transit ion State Structure E. Theoretical Calculat ions on Thiol-Disulhde Interchanse F. Mechanist ic Uncertaint ies . .

Preeclampsia: 2-methoxyestradiol induces cytotrophoblast invasion and vascular development specifically under hypoxic conditions.

Abstract: Inadequate invasion of the uterus by cytotrophoblasts is speculated to result in pregnancy-induced disorders such as preeclampsia. However, the molecular mechanisms that govern appropriate invasion of cytotrophoblasts are unknown. Here, we demonstrate that under low-oxygen conditions (2.5% oxygen), 2-methoxyestradiol (2-ME), which is a metabolite of estradiol and is generated by catechol-o-methyltransferase (COMT), induces invasion of cytotrophoblasts into a naturally-derived, extracellular matrix. Neither low-oxygen conditions nor 2-ME alone induces the invasion of cytotrophoblasts in this system; however, low-oxygen conditions combined with 2-ME result in the appropriate invasion of cytotrophoblasts into the extracellular matrix. Cytotrophoblast invasion under these conditions is also associated with a decrease in the expression of hypoxia-inducible factor-1α (HIF-1α), transforming growth factor-β3 (TGF-β3), and tissue inhibitor of metalloproteinases-2 (TIMP-2). Pregnant COMT-deficient mice with hypoxic placentas and preeclampsia-like features demonstrate an up-regulation of HIF-1α, TGF-β3, and TIMP-2 when compared with wild-type mice; normal levels are restored on administration of 2-ME, which also results in the resolution of preeclampsia-like features in these mice. Indeed, placentas from patients with preeclampsia reveal lower levels of COMT and higher levels of HIF-1α, TGF-β3, and TIMP-2 when compared with those from normal pregnant women. We demonstrate that low-oxygen conditions of the placenta are a critical co-stimulator along with 2-ME for the proper invasion of cytotrophoblasts to facilitate appropriate vascular development and oxygenation during pregnancy.

Micro- and Nanopatterning of Inorganic and Polymeric Substrates by Indentation Lithography

Abstract: This paper describes the use of a nanoindenter, equipped with a diamond tip, to form patterns of indentations on planar substrates (epoxy, silicon, and SiO2). The process is called “Indentation Lit...

Fabrication and Replication of Arrays of Single- or Multicomponent Nanostructures by Replica Molding and Mechanical Sectioning

Abstract: This paper describes the fabrication of arrays of nanostructures (rings, crescents, counterfacing split rings, cylinders, coaxial cylinders, and other structures) by a four-step process: (i) molding an array of epoxy posts by soft lithography, (ii) depositing thin films on the posts, (iii) embedding the posts in epoxy, and (iv) sectioning in a plane parallel to the plane defined by the array of posts, into slabs, with an ultramicrotome (“nanoskiving”). This work demonstrates the combination of four capabilities: (i) formation of structures that are submicrometer in all dimensions; (ii) fabrication of 3D structures, and arrays of structures, with gradients of height; (iii) patterning of arrays containing two or more materials, including metals, semiconductors, oxides, and polymers; and (iv) generation of as many as 60 consecutive slabs bearing contiguous arrays of nanostructures. These arrays can be transferred to different substrates, and arrays of gold rings exhibit plasmonic resonances in the range of w...

Millimeter-scale contact printing of aqueous solutions using a stamp made out of paper and tape

Abstract: This communication describes a simple method for printing aqueous solutions with millimeter-scale patterns on a variety of substrates using an easily fabricated, paper-based microfluidic device (a paper-based “stamp”) as a contact printing device. The device is made from inexpensive materials, and it is easily assembled by hand; this method is thus accessible to a wide range of laboratories and budgets. A single device was used to print over 2500 spots in less than three minutes at a density of 16 spots per square centimetre. This method provides a new tool to pattern biochemicals—reagents, antigens, proteins, and DNA—on planar substrates. The accuracy of the volume of fluid delivered in simple paper-to-paper printing is low, and although the pattern transfer is rapid, it is better suited for qualitative than accurate, quantitative work. By patterning the paper to which the transfer occurs using wax printing or an equivalent technique, accuracy increases substantially.

Rapid prototyping of microstructures by soft lithography for biotechnology.

Abstract: This chapter describes the methods and specific procedures used to fabricate microstructures by soft lithography. These techniques are useful for the prototyping of devices useful for applications in biotechnology. Fabrication by soft lithography does not require specialized or expensive equipment; the materials and facilities necessary are found commonly in biological and chemical laboratories in both academia and industry. The combination of the fact that the materials are low-cost and that the time from design to prototype device can be short (< 24 h) makes it possible to use and to screen rapidly devices that also can be disposable. Here we describe the procedures for fabricating microstructures with lateral dimensions as small as 1 mum. These types of microstructures are useful for microfluidic devices, cell-based assays, and bioengineered surfaces.

Uniform Amplification of Phage with Different Growth Characteristics in Individual Compartments Consisting of Monodisperse Droplets

Abstract: Uniform amplification of a mixture of phage clones is central to the selection of peptides and proteins presented on the coat proteins of phage (phage display).[1,2] Uniform amplification cannot be achieved when phage having different rates of growth compete with each other in a common solution. Here we describe a method for uniform amplification of individual phage clones, from a mixture of clones possessing different growth characteristics. We use a microfluidic droplet generator[3] to separate individual clones from a mixture of slowly growing (S) and rapidly growing (R) M13 filamentous phage into droplets of growth media (ca. 200 µm in diameter) containing E. coli. At sufficiently low concentrations of phage, each droplet contains one or no phage particles. Different phage cannot compete for bacterial hosts when isolated in different droplets, and the relative number of S and R clones present at the start is preserved after amplification. Because amplification of phage clones depends on the size of the droplets in which they reside, the use of droplets of uniform size is essential for the success of this process.

Cofabrication: A Strategy for Building Multicomponent Microsystems

Abstract: This Account describes a strategy for fabricating multicomponent microsystems in which the structures of essentially all of the components are formed in a single step of micromolding. This strategy, which we call “cofabrication”, is an alternative to multilayer microfabrication, in which multiple layers of components are sequentially aligned (“registered”) and deposited on a substrate by photolithography. Cofabrication has several characteristics that make it an especially useful approach for building multicomponent microsystems. It rapidly and inexpensively generates correctly aligned components (for example, wires, heaters, magnetic field generators, optical waveguides, and microfluidic channels) over very large surface areas. By avoiding registration, the technique does not impose on substrates the size limitations of common registrations tools, such as steppers and contact aligners. We have demonstrated multicomponent microsystems with surface areas exceeding 100 cm2, but in principle, device size is ...

Patterning precipitates of reactions in paper

Abstract: This article describes a method for patterning certain solids—insoluble salts and reduced metals—in sheets of paper. Chemical reactions that produce these solids as precipitates occur when a stamp of patterned paper inked with an aqueous solution of reagent comes into contact with a paper substrate containing a second reagent. The pattern is determined by a hydrophobic barrier on the stamp that restricts delivery of the ink in two dimensions. The technique is one of the few methods available to generate two-dimensional patterns of solids within the bulk of sheets of paper. It can reliably produce features with lateral dimensions only down to 1 mm, but is convenient, inexpensive, and amenable to use in large-area patterning. The method can be used to introduce function to paper-based systems: (i) paramagnetic salts precipitated within paper allow pieces of it to be manipulated or separated from mixtures with a bar magnet, (ii) the precipitation of transition metals or enzymes can be used to position and store catalysts on paper for subsequent use, (iii) catalysts patterned in two dimensions in paper can be used to generate dynamic 3-D structures when exposed to appropriate substrates: for example, a ring of Pd0 deposited on a sheet of paper will generate a cylindrical “cage” of rising oxygen bubbles when exposed to an aqueous solution of hydrogen peroxide, and (iv) patterns of catalysts or colored precipitates can serve as deterrents to counterfeiting.

Patterned paper as a template for the delivery of reactants in the fabrication of planar materials

Abstract: This account reviews the use of templates, fabricated by patterning paper, for the delivery of aqueous solutions of reactants (predominantly, ions) in the preparation of structured, thin materials (e.g., films of ionotropic hydrogels). In these methods, a patterned sheet of paper transfers an aqueous solution of reagent to a second phase—either solid or liquid—brought into contact with the template; this process can form solid structures with thicknesses that are typically ≤1.5 mm. The shape of the template and the pattern of a hydrophobic barrier on the paper control the shape of the product, in its plane, by restricting the delivery of the reagent in two dimensions. The concentration of the reagents, and the duration that the template remains in contact with the second phase, control growth in the third dimension (i.e., thickness). The method is especially useful in fabricating shaped films of ionotropic hydrogels (e.g., calcium alginate) by controlling the delivery of solutions of multivalent cations to solutions of anionic polymers. The templates can also be used to direct reactions that generate patterns of solid precipitates within sheets of paper. This review examines applications of the method for: (i) patterning bacteria in two dimensions within a hydrogel film, (ii) manipulating hydrogel films and sheets of paper magnetically, and (iii) generating dynamic 3-D structures (e.g., a cylinder of rising bubbles of O2) from sheets of paper with 2-D patterns of a catalyst (e.g., Pd0) immersed in appropriate reagents (e.g., 1% H2O2 in water).

Formation of Bubbles in a Multisection Flow-Focusing Junction

Abstract: The formation of bubbles in a flow-focusing (FF) junction comprising multiple rectangular sections is described. The simplest junctions comprise two sections (throat and orifice). Systematic investigation of the influence on the formation of bubbles of the flow of liquid and the geometry of the junction identifies regimes that generate monodisperse, bidisperse, and tridisperse trains of bubbles. The mechanisms by which these junctions form monodisperse and bidisperse bubbles are inferred from the shapes of the gas thread during breakup: these mechanisms differ primarily by the process in which the gas thread collapses in the throat and/or orifice. The dynamic self-assembly of bidisperse bubbles leads to unexpected groupings of bubbles during their flow along the outlet channel.

Survey of Materials for Nanoskiving and Influence of the Cutting Process on the Nanostructures Produced

Abstract: This paper examines the factors that influence the quality of nanostructures fabricated by sectioning thin films with an ultramicrotome ("nanoskiving"). It surveys different materials (metals, ceramics, semiconductors, and conjugated polymers), deposition techniques (evaporation, sputter deposition, electroless deposition, chemical-vapor deposition, solution-phase synthesis, and spin-coating), and geometries (nanowires or two-dimensional arrays of rings and crescents). It then correlates the extent of fragmentation of the nanostructures with the composition of the thin films, the methods used to deposit them, and the parameters used for sectioning. There are four major conclusions. (i) Films of soft and compliant metals (those that have bulk values of hardness less than or equal to those of palladium, or ≤500 MPa) tend to remain intact upon sectioning, whereas hard and stiff metals (those that have values of hardness greater than or equal to those of platinum, or ≥500 MPa) tend to fragment. (ii) All conjugated polymers tested form intact nanostructures. (iii) The extent of fragmentation is lowest when the direction of cutting is perpendicular to the exposed edge of the embedded film. (iv) The speed of cutting-from 0.1 to 8 mm/s-has no effect on the frequency of defects. Defects generated during sectioning include scoring from defects in the knife, delamination of the film from the matrix, and compression of the matrix. The materials tested were: aluminum, titanium, nickel, copper, palladium, silver, platinum, gold, lead, bismuth, germanium, silicon dioxide (SiO2), alumina (Al2O3), tin-doped indium oxide (ITO), lead sulfide nanocrystals, the semiconducting polymers poly(2-methoxy-5-(2'-ethyl-hexyloxy)-1,4-phenylene vinylene) (MEH-PPV), poly(3-hexylthiophene) (P3HT), and poly(benzimidazobenzophenanthroline ladder) (BBL), and the conductive polymer poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS).

Neutralizing positive charges at the surface of a protein lowers its rate of amide hydrogen exchange without altering its structure or increasing its thermostability.

Abstract: This paper combines two techniquessmass spectrometry and protein charge ladderssto examine the relationship between the surface charge and hydrophobicity of a representative globular protein (bovine carbonic anhydrase II; BCA II) and its rate of amide hydrogen-deuterium (H/D) exchange. Mass spectrometric analysis indicated that the sequential acetylation of surface lysine-e-NH3 + groupssa type of modification that increases the net negative charge and hydrophobicity of the surface of BCA II without affecting its secondary or tertiary structuresresulted in a linear decrease in the aggregate rate of amide H/D exchange at pD 7.4, 15 °C. According to analysis with MS, the acetylation of each additional lysine generated between 1.4 and 0.9 additional hydrogens that are protected from H/D exchange during the 2 h exchange experiment at 15 °C, pD 7.4. NMR spectroscopy demonstrated that none of the hydrogen atoms which became protected upon acetylation were located on the side chain of the acetylated lysine residues (i.e., lys-e-NHCOCH3) but were instead located on amide NHCO moieties in the backbone. The decrease in rate of exchange associated with acetylation paralleled a decrease in thermostability: the most slowly exchanging rungs of the charge ladder were the least thermostable (as measured by differential scanning calorimetry). This observationsthat faster rates of exchange are associated with slower rates of denaturationsis contrary to the usual assumptions in protein chemistry. The fact that the rates of H/D exchange were similar for perbutyrated BCA II (e.g., (lys-e-NHCO(CH2)2CH3)18) and peracetylated BCA II (e.g., (lys-e-NHCOCH3)18) suggests that the electrostatic charge is more important than the hydrophobicity of surface groups in determining the rate of H/D exchange. These electrostatic effects on the kinetics of H/D exchange could complicate (or aid) the interpretation of experiments in which H/D exchange methods are used to probe the structural effects of non-isoelectric perturbations to proteins (i.e., phosphorylation, acetylation, or the binding of the protein to an oligonucleotide or to another charged ligand or protein).

Control over Rectification in Supramolecular Tunneling Junctions

Abstract: In complete control: The magnitude of current rectification in well-defined supramolecular tunneling junctions can be controlled by changing the terminal functionality (red spheres) of dendrimers (gray spheres) immobilized on a supramolecular platform (see picture). Junctions containing biferrocene and ferrocene end groups showed larger rectification ratios than junctions containing adamantyl end groups.

Subnanometer replica molding of molecular steps on ionic crystals.

Abstract: Replica molding with elastomeric polymers has been used routinely to replicate features less than 10 nm in size. Because the theoretical limit of this technique is set by polymer-surface interactions, atomic radii, and accessible volumes, replication at subnanometer length scales should be possible. Using polydimethylsiloxane to create a mold and polyurethane to form the replica, we demonstrate replication of elementary steps 3-5 A in height that define the minimum separation between molecular layers in the lattices of the ionic crystals potassium dihydrogen phosphate and calcite. This work establishes the operation of replica molding at the molecular scale.

Microfluidic, electrochemical devices

Abstract: Microfluidic, electrochemical devices are described. The microfluidic, electrochemical device comprises one or more electrode(s) on a substrate and a patterned porous, hydrophilic layer having a fluid-impermeable barrier which substantially permeates the thickness of the porous, hydrophilic layer and defines boundaries of one or more hydrophilic channels within the patterned porous, hydrophilic layer, wherein the hydrophilic channel(s) comprises a hydrophilic region which is in fluidic communication with the electrode(s). In some embodiments, the electrodes comprise a working electrode, a counter electrode, and a reference electrode. In some embodiments, the microfluidic, electrochemical device further comprises a fluid sink. The method of assembling the microfluidic, electrochemical device is described. The method of using the device for electrochemical analysis of one or more analytes is also described.