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Ricin is a toxin that could potentially be used as a bioweapon. We identified anti-ricin A chain antibodies by sequencing the antibody repertoire from immunized mice and by selecting high affinity antibodies using yeast surface display. These methods led to the isolation of multiple antibodies with high (sub-nanomolar) affinity. Interestingly, the antibodies identified by the 2 independent approaches are from the same clonal lineages, indicating for the first time that yeast surface display can identify native antibodies. The new antibodies represent well-characterized reagents for biodefense diagnostics and therapeutics development.

Herein the problem of colloidal instability on electrochemically detected nanoparticle (NP) collisions with a Hg ultramicroelectrode (UME) by electrocatalytic amplification is addressed. NP tracking analysis (NTA) shows that rapid aggregation occurs in solution after diluting citrate-stabilized Pt NPs with hydrazine/phosphate buffers of net ionic strength greater than 70 mM. Colloidal stability improves by lowering the ionic strength, indicating that aggregation processes were strongly affected by charge screening of the NP double layer interactions at high cation concentrations. For the system of lowest ionic strength, the overwhelming majority of observed electrocatalytic current signals represent single NP/electrode impacts, as confirmed by NTA kinetic monitoring. NP diffusion coefficients determined by NTA and NP impact electroanalysis are in excellent agreement for the stable colloids, which signifies that the sticking probability of Pt NPs interacting with Hg is unity and that the observed NP impact rate agrees with the expected steady-state diffusive flux expression for the spherical cap Hg UME.

In the last decade, paper analytical devices (PADs) have evolved into sophisticated yet simple sensors with biological and environmental applications in the developed and developing world. The focus of this review is the technological improvements that have over the past five years increased the applicability of PADs to real-world problems. Specifically, this review reports on advances in sample processing, fluid flow control, signal amplification, and component integration. Throughout, we have sought to emphasize advances that retain the main virtues of PADs: low cost, portability, and simplicity.

Electrocatalytic oxygen reduction at carbon electrodes fully passivated by Al2O3 is reported. Specifically, pyrolyzed polymer film (PPF) electrodes were prepared and then coated with pinhole-free Al2O3 layers ranging in thickness from 2.5 to 5.7 nm. All of these ultrathin oxide film thicknesses completely passivated the PPF electrodes, resulting in no faradaic current for either inner-sphere or outer-sphere electrochemical reactions. The electrodes could, however, be reactivated by immobilizing Pt dendrimer-encapsulated nanoparticles (DENs), containing an average of 55 atoms each, on the oxide surface. These PPF/Al2O3/Pt DEN electrodes were completely stable under a variety of electrochemical and solution conditions, and they are active for simple electron-transfer reactions and for more complex electrocatalytic processes. This approach for preparing well-defined oxide electrodes opens the door to a better understanding of the effect of oxide supports on reactions electrocatalyzed by metal nanoparticles.

We present an effective numerical approach to simulate electrochemically mediated desalination of seawater. This new membraneless, energy efficient desalination method relies on the oxidation of chloride ions, which generates an ion depletion zone and local electric field gradient near the junction of a microchannel branch to redirect sea salt into the brine stream, consequently producing desalted water. The proposed numerical model is based on resolution of the 3D coupled Navier-Stokes, Nernst-Planck, and Poisson equations at non-uniform spatial grids. The model is implemented as a parallel code and can be employed to simulate mass-charge transport coupled with surface or volume reactions in 3D systems showing an arbitrarily complex geometrical configuration.

We report a paper-based assay platform for the detection of the kidney disease marker Trefoil Factor 3 (TFF3) in human urine. The sensor is based on a quantitative metalloimmunoassay that can determine TFF3 concentrations via electrochemical detection of environmentally stable silver nanoparticle (AgNP) labels attached to magnetic microbeads via a TFF3 immunosandwich. The paper electroanalytical device incorporates two preconcentration steps that make it possible to detect concentrations of TFF3 in human urine at the low end of the target TFF3 concentration range (0.03-7.0 μg mL(-1)). Importantly, the paper device provides a level of accuracy for TFF3 determination in human urine equivalent to that of a commercial kit. The paper sensor has a dynamic range of ∼2.5 orders of magnitude, only requires a simple, one-step incubation protocol, and is fast, requiring only 10 min to complete. The cost of the materials at the prototypic laboratory scale, excluding reagents, is just US$0.42.

Here, we report on the electrochemical detection of individual collisions between a conjugate consisting of silver nanoparticles (AgNPs) linked to conductive magnetic microbeads (cMμBs) via DNA hybridization and a magnetized electrode. The important result is that the presence of the magnetic field increases the flux of the conjugate to the electrode surface, and this in turn increases the collision frequency and improves the limit of detection (20 aM). In addition, the magnitude of the charge associated with the collisions is greatly enhanced in the presence of the magnetic field. The integration of DNA into the detection protocol potentially provides a means for using electrochemical collisions for applications in biological and chemical sensing.

Here we report on the effect of DNA modification on individual collisions between Pt nanoparticles (PtNPs) and ultramicroelectrode (UME) surfaces. These results extend recent reports of electrocatalytic amplification (ECA) arising from collisions between naked surfaces, and they are motivated by our interest in using ECA for low-level biosensing applications. In the present case, we studied collisions between naked PtNPs and DNA-modified Au and Hg UMEs and also collisions between DNA-modified PtNPs and naked Au and Hg UMEs. In all cases, the sensing reaction is the catalytic oxidation of N2H4. The presence of ssDNA (5-mer or 25-mer) immobilized on the UME surface has little effect on the magnitude or frequency of ECA signals, regardless of whether the electrode is Au or Hg. In contrast, when DNA is immobilized on the PtNPs and the electrodes are naked, clear trends emerge. Specifically, as the surface concentration of ssDNA on the PtNP surface increases, the magnitude and frequency of the current transients decrease. This trend is most apparent for the longer 25-mer. We interpret these results as follows. When ssDNA is immobilized at high concentration on the PtNPs, the surface sites on the NP required for electrocatalytic N2H4 oxidation are blocked. This leads to lower and fewer ECA signals. In contrast, naked PtNPs are able to transfer electrons to UMEs having sparse coatings of ssDNA.

We present a new paper-based isotachophoresis (ITP) device design for focusing DNA samples having lengths ranging from 23 to at least 1517 bp. DNA is concentrated by more than two orders of magnitude within 4 min. The key component of this device is a 2 mm-long, 2 mm-wide circular paper channel formed by concertina folding a paper strip and aligning the circular paper zones on each layer. Due to the short channel length, a high electric field of ~16 kV m(-1) is easily generated in the paper channel using two 9 V batteries. The multilayer architecture also enables convenient reclamation and analysis of the sample after ITP focusing by simply opening the origami paper and cutting out the desired layers. We profiled the electric field in the origami paper channel during ITP experiments using a nonfocusing fluorescent tracer. The result showed that focusing relied on formation and subsequent movement of a sharp electric field boundary between the leading and trailing electrolyte.

To create truly effective electrocatalysts for the cathodic reaction governing proton exchange membrane fuel cells (PEMFC), namely the oxygen reduction reaction (ORR), necessitates an accurate and detailed structural understanding of these electrocatalysts, especially at the nanoscale, and to precisely correlate that structure with demonstrable performance enhancement. To address this key issue, we have combined and interwoven theoretical calculations with experimental, spectroscopic observations in order to acquire useful structural insights into the active site geometry with implications for designing optimized nanoscale electrocatalysts with rationally predicted properties. Specifically, we have probed ultrathin (∼2 nm) core-shell Pt∼Pd9Au nanowires, which have been previously shown to be excellent candidates for ORR in terms of both activity and long-term stability, from the complementary perspectives of both DFT calculations and X-ray absorption spectroscopy (XAS). The combination and correlation of data from both experimental and theoretical studies has revealed for the first time that the catalytically active structure of our ternary nanowires can actually be ascribed to a PtAu∼Pd configuration, comprising a PtAu binary shell and a pure inner Pd core. Moreover, we have plausibly attributed the resulting structure to a specific synthesis step, namely the Cu underpotential deposition (UPD) followed by galvanic replacement with Pt. Hence, the fundamental insights gained into the performance of our ultrathin nanowires from our demonstrated approach will likely guide future directed efforts aimed at broadly improving upon the durability and stability of nanoscale electrocatalysts in general.

Here we show that a simple paper-based electrochemical sensor, fabricated by paper folding, is able to detect a 30-base nucleotide sequence characteristic of DNA from the hepatitis B virus (HBV) with a detection limit of 85 pM. This device is based on design principles we have reported previously for detecting proteins via a metalloimmunoassay. It has four desirable attributes. First, its design combines simple origami (paper folding) assembly, the open structure of a hollow-channel paper analytical device to accommodate micrometer-scale particles, and a convenient slip layer for timing incubation steps. Second, two stages of amplification are achieved: silver nanoparticle labels provide a maximum amplification factor of 250 000 and magnetic microbeads, which are mobile solid-phase supports for the capture probes, are concentrated at a detection electrode and provide an additional ∼25-fold amplification. Third, there are no enzymes or antibodies used in the assay, thereby increasing its speed, stability, and robustness. Fourth, only a single sample incubation step is required before detection is initiated.

An integrated microfluidic/magnetophoretic methodology was developed for improving signal response time and detection limits for the chronoamperometric observation of discrete nanoparticle/electrode interactions by electrocatalytic amplification. The strategy relied on Pt-decorated iron oxide nanoparticles which exhibit both superparamagnetism and electrocatalytic activity for the oxidation of hydrazine. A wet chemical synthetic approach succeeded in the controlled growth of Pt on the surface of FeO/Fe3O4 core/shell nanocubes, resulting in highly uniform Pt-decorated iron oxide hybrid nanoparticles with good dispersibility in water. The unique mechanism of hybrid nanoparticle formation was investigated by electron microscopy and spectroscopic analysis of isolated nanoparticle intermediates and final products. Discrete hybrid nanoparticle collision events were detected in the presence of hydrazine, an electrochemical indicator probe, using a gold microband electrode integrated into a microfluidic channel. In contrast with related systems, the experimental nanoparticle/electrode collision rate correlates more closely with simple theoretical approximations, primarily due to the accuracy of the nanoparticle tracking analysis method used to quantify nanoparticle concentrations and diffusion coefficients. Further modification of the microfluidic device was made by applying a tightly focused magnetic field to the detection volume to attract the magnetic nanoprobes to the microband working electrode, thereby resulting in a 6-fold increase to the relative frequency of chronoamperometric signals corresponding to discrete nanoparticle impact events.

A theoretical and experimental study of the electrocatalytic oxidation of CO on PdxAu140-x@Pt dendrimer-encapsulated nanoparticle (DEN) catalysts is presented. These nanoparticles are comprised of a core having an average of 140 atoms and a Pt monolayer shell. The CO oxidation activity trend exhibits an unusual koppa shape as the number of Pd atoms in the core is varied from 0 to 140. Calculations based on density functional theory suggest that the koppa-shaped trend is driven primarily by structural changes that affect the CO binding energy on the surface. Specifically, a pure Au core leads to deformation of the Pt shell and a compression of the Pt lattice. In contrast, Pd, from the pure Pd cores, tends to segregate on the DEN surface, forming an inverted configuration having Pt within the core and Pd in the shell. With a small addition of Au, however, the alloy PdAu cores stabilize the core@shell structures by preventing Au and Pd from escaping to the particle surface.

The synthesis and characterization of Sn nanoparticles in organic solvents using sixth-generation dendrimers modified on their periphery with hydrophobic groups as stabilizers are reported. Sn(2+):dendrimer ratios of 147 and 225 were employed for the synthesis, corresponding to formation of Sn147 and Sn225 dendrimer-stabilized nanoparticles (DSNs). Transmission electron microscopy analysis indicated the presence of ultrasmall Sn nanoparticles having an average size of 3.0-5.0 nm. X-ray absorption spectroscopy suggested the presence of Sn nanoparticles with only partially oxidized surfaces. Cyclic voltammetry studies of the Sn DSNs for Li alloying/dealloying reactions demonstrated good reversibility. Control experiments carried out in the absence of DSNs clearly indicated that these ultrasmall Sn DSNs react directly with Li to form SnLi alloys.

The objective of the research described in this Account is the development of high-throughput computational-based screening methods for discovery of catalyst candidates and subsequent experimental validation using appropriate catalytic nanoparticles. Dendrimer-encapsulated nanoparticles (DENs), which are well-defined 1-2 nm diameter metal nanoparticles, fulfill the role of model electrocatalysts. Effective comparison of theory and experiment requires that the theoretical and experimental models map onto one another perfectly. We use novel synthetic methods, advanced characterization techniques, and density functional theory (DFT) calculations to approach this ideal. For example, well-defined core@shell DENs can be synthesized by electrochemical underpotential deposition (UPD), and the observed deposition potentials can be compared to those calculated by DFT. Theory is also used to learn more about structure than can be determined by analytical characterization alone. For example, density functional theory molecular dynamics (DFT-MD) was used to show that the core@shell configuration of Au@Pt DENs undergoes a surface reconstruction that dramatically affects its electrocatalytic properties. A separate Pd@Pt DENs study also revealed reorganization, in this case a core-shell inversion to a Pt@Pd structure. Understanding these types of structural changes is critical to building correlations between structure and catalytic function. Indeed, the second principal focus of the work described here is correlating structure and catalytic function through the combined use of theory and experiment. For example, the Au@Pt DENs system described earlier is used for the oxygen reduction reaction (ORR) as well as for the electro-oxidation of formic acid. The surface reorganization predicted by theory enhances our understanding of the catalytic measurements. In the case of formic acid oxidation, the deformed nanoparticle structure leads to reduced CO binding energy and therefore improved oxidation activity. The final catalytic study we present is an instance of theory correctly predicting (in advance of the experiments) the structure of an effective DEN electrocatalyst. Specifically, DFT was used to determine the optimal composition of the alloy-core in AuPd@Pt DENs for the ORR. This prediction was subsequently confirmed experimentally. This study highlights the major theme of our research: the progression of using theory to rationalize experimental results to the more advanced goal of using theory to predict catalyst function a priori. We still have a long way to go before theory will be the principal means of catalyst discovery, but this Account begins to shed some light on the path that may lead in that direction.

We present a method for quantifying the accuracy of extended X-ray absorption fine structure (EXAFS) fitting models. As a test system, we consider the structure of bare Au147 nanoparticles as well as particles bound with thiol ligands, which are used to systematically vary disorder in the atomic structure of the nanoparticles. The accuracy of the fitting model is determined by comparing two distributions of bond lengths: (1) a direct average over a molecular dynamics (MD) trajectory using forces and energies from density functional theory (DFT) and (2) a fit to the theoretical EXAFS spectra generated from that same trajectory. Both harmonic and quasi-harmonic EXAFS fitting models are used to characterize the first-shell Au-Au bond length distribution. The harmonic model is found to significantly underestimate the coordination number, disorder, and bond length. The quasi-harmonic model, which includes the third cumulant of the first-shell bond length distribution, yields accurate bond lengths, but incorrectly predicts a decrease in particle size and little change in the disorder with increasing thiol ligands. A direct analysis of the MD data shows that the particle surfaces become much more disordered with ligand binding, and the high disorder is incorrectly interpreted by the EXAFS fitting models. Our DFT calculations compare well with experimental EXAFS measurements of Au nanoparticles, synthesized using a dendrimer encapsulation technique, showing that systematic errors in EXAFS fitting models apply to nanoparticles 1-2 nm in size. Finally we show that a combination of experimental EXAFS analysis with candidate models from DFT is a promising strategy for a more accurate determination of nanoparticle structures.

We report electrochemical catalytic amplification of individual collisions between ∼57 nm diameter Pt nanoparticles (Pt NPs) and 12.5 μm diameter Au ultramicroelectrodes modified with passivating, electrostatically assembled polyelectrolyte multilayer (PEM) films prepared by the layer-by-layer deposition method. Two key findings are reported. First, despite the thicknesses of the insulating PEM films, which range up to 5 nm, electrons are able to tunnel from the Pt NPs to the electrode resulting in electrocatalytic N2H4 oxidation at the PEM film-solution interface. These single-particle measurements are in accord with prior reports showing that the electrochemical activity of passive PEM films can be reactivated by adsorption of metallic NPs. Second, it is possible to control the frequency of the collisions by manipulating the net electrostatic charge present on the outer surface of the PEM thin film. These results, which demonstrate that chemistry can be used to control electrocatalytic amplification, set the stage for future sensing applications.

We report a paper-based assay platform for detection of ricin a chain. The paper platform is assembled by simple origami paper folding. The sensor is based on quantitative, electrochemical detection of silver nanoparticle labels linked to a magnetic microbead support via a ricin immunosandwich. Importantly, ricin was detected at concentrations as low as 34 pM. Additionally, the assay is robust, even in the presence of 100-fold excess hoax materials. Finally, the device is easily remediated after use by incineration. The cost of the device, not including reagents, is just $0.30. The total assay time, including formation of the immunosandwich, is 9.5 min.

We present an origami paper-based electrophoretic device (oPAD-Ep) that achieves rapid (∼5 min) separation of fluorescent molecules and proteins. Due to the innovative design, the required driving voltage is just ∼10 V, which is more than 10 times lower than that used for conventional electrophoresis. The oPAD-Ep uses multiple, thin (180 μm/layer) folded paper layers as the supporting medium for electrophoresis. This approach significantly shortens the distance between the anode and cathode, and this, in turn, accounts for the high electric field (>1 kV/m) that can be achieved even with a low applied voltage. The multilayer design of the oPAD-Ep enables convenient sample introduction by use of a slip layer as well as easy product analysis and reclamation after electrophoresis by unfolding the origami paper and cutting out desired layers. We demonstrate the use of oPAD-Ep for simple separation of proteins in bovine serum, which illustrates its potential applications for point-of-care diagnostic testing.

Here we outline a new method for synthesizing fully reduced Pt dendrimer-encapsulated nanoparticles (DENs). This is achieved by first synthesizing Cu DENs of the appropriate size through sequential dendrimer loading and reduction steps, and then galvanically exchanging the zerovalent Cu DENs for Pt. The properties of Pt DENs having an average of 55, 140, and 225 atoms prepared by direct chemical reduction and by galvanic exchange are compared. Data obtained by UV-vis spectroscopy, X-ray absorption spectroscopy, X-ray photoelectron spectroscopy, and high-resolution electron microscopy confirm only the presence of fully reduced Pt DENs when synthesized by galvanic exchange, while chemical reduction leads to a mixture of reduced DENs and unreduced precursor. These results are significant because Pt DENs are good models for developing a better understanding of the effects of finite size on catalytic reactions. Until now, however, the results of such studies have been complicated by a heterogeneous mixture of Pt catalysts.

Here we report on the electrochemical properties of carbon electrodes coated with thin layers of Al2O3 and SnO2. These oxide films were deposited using atomic layer deposition (ALD) and range in thickness from 1 to 6 nm. Electrochemical experiments show that the thinnest oxide layers contain defects that penetrate to the underlying carbon electrode. However, oxygenation of the carbon surface prior to ALD increases the surface concentration of nucleation sites for oxide growth and suppresses the defect density. Films of Al2O3 just ∼3-4 nm in thickness are free of pinholes. Slightly thicker coatings of SnO2 are required for equivalent passivation. Both Al2O3 and SnO2 films are stable in both neutral and acidic electrolytes even after repeated voltammetric scanning. The results reported here open up the possibility of studying the effect of oxide supports on electrocatalytic reactions.

We report on the effect of convection on electrochemically active collisions between individual Pt nanoparticles (PtNPs) and Hg and Au electrodes. Compared to standard electrochemical cells utilizing Hg and Au ultramicroelectrodes (UMEs) used in previous studies of electrocatalytic amplification, microelectrochemical devices offer two major advantages. First, the PtNP limit of detection (0.084 pM) is ∼8 times lower than the lowest concentration measured using UMEs. Second, convection enhances the mass transfer of PtNPs to the electrode surface, which enhances the collision frequency from ∼0.02 pM(-1) s(-1) on UMEs to ∼0.07 pM(-1) s(-1) in microelectrochemical devices. We also show that the size of PtNPs can be measured in flowing systems using data from collision experiments and then validate this finding using multiphysics simulations.

Here we report on the development of a high-efficiency, dual channel-electrode (DCE) generation-collection system and its application for interrogating redox-active surface-adsorbed thin films. DCE systems consist of two electrodes configured on the base of a microfluidic channel. Under laminar flow conditions, a redox reaction can be driven on the upstream generator electrode, and the products carried by convection to the downstream collector electrode where the reverse redox reaction occurs. One significant outcome of this report is that simple fabrication techniques can be used to prepare DCE systems that have collection efficiencies of up to 97%. This level of efficiency makes it possible to quantitatively measure the charge associated with redox-active thin films interposed between the generator and collector electrodes. This is important, because it provides a means for interrogating species that are not in sufficiently close proximity to an electrode to enable direct electron transfer or electroactive films adsorbed to insulating surfaces. Here, the method is demonstrated by comparing results from this indirect surface interrogation method, using Fe(CN)6(3-) as the redox probe, and direct electroreduction of Au oxide thin films. These experimental results are further compared to finite-element simulations.

We report a new type of paper analytical device that provides quantitative electrochemical output and detects concentrations as low as 767 fM. The model analyte is labeled with silver nanoparticles (AgNPs), which provide 250,000-fold amplification. AgNPs eliminate the need for enzymatic amplification, thereby improving device stability and response time. The use of magnetic beads to preconcentrate the AgNPs at the detection electrode further improves sensitivity. Response time is improved by incorporation of a hollow channel, which increases the flow rate in the device by a factor of 7 and facilitates the use of magnetic beads. A key reaction necessary for label detection is made possible by the presence of a slip layer, a fluidic switch that can be actuated by manually slipping a piece of paper. The design of the device is versatile and should be useful for detection of proteins, nucleic acids, and microbes.

Here, we report a strategy for the design of an inexpensive paper analytical device (PAD) for quantitative detection of oligonucleotides and proteins. Detection is based on the principle of target-induced conformational switching of an aptamer linked to an electrochemical label. This simple and robust method is well matched to the equally simple and robust characteristics of the PAD platform. The demonstrated limits of detection for DNA and thrombin are 30 nM and 16 nM, respectively, and the device-to-device reproducibility is better than ±10%. The PAD has a shelf life of at least 4 weeks, involves little user intervention, and requires a sample volume of just 20 μL.

In this paper we describe a method for three-dimensional wax patterning of microfluidic paper-based analytical devices (μPADs). The method is rooted in the fundamental details of wax transport in paper and provides a simple way to fabricate complex channel architectures such as hemichannels and fully enclosed channels. We show that three-dimensional μPADs can be fabricated with half as much paper by using hemichannels rather than ordinary open channels. We also provide evidence that fully enclosed channels are efficiently isolated from the exterior environment, decreasing contamination risks, simplifying the handling of the device, and slowing evaporation of solvents.

We report electrochemical detection of collisions between individual magnetic microbeads, present at subattomolar concentrations, and electrode surfaces. This limit of detection is 4 orders of magnitude lower than has been reported previously, and it is enabled by using a magnetic field to preconcentrate the microbeads prior to detection in a microfluidic electrochemical cell. Importantly, the frequency of collisions between the microbeads and the electrode is not compromised by the low concentration of microbeads. These findings represent an unusual case of detecting individual electrochemical events at very low analyte concentration. In addition to experiments supporting these claims, finite-element simulations provide additional insights into the nature of the interactions between flowing microbeads and their influence on electrochemical processes.

Here, we report the use of microwire and mesh working electrodes in paper analytical devices fabricated by origami paper folding (oPADs). The important new result is that Au wires and carbon fibers having diameters ranging from micrometers to tens of micrometers can be incorporated into oPADs and that their electrochemical characteristics are consistent with the results of finite element simulations. These electrodes are fully compatible with both hollow channels and paper channels filled with cellulose fibers, and they are easier to incorporate than typical screen-printed carbon electrodes. The results also demonstrate that the Au electrodes can be cleaned prior to device fabrication using aggressive treatments and that they can be easily surface modified using standard thiol-based chemistry.

In the present article we provide a detailed analysis of fundamental electrochemical processes in a new class of paper-based analytical devices (PADs) having hollow channels (HCs). Voltammetry and amperometry were applied under flow and no flow conditions yielding reproducible electrochemical signals that can be described by classical electrochemical theory as well as finite-element simulations. The results shown here provide new and quantitative insights into the flow within HC-PADs. The interesting new result is that despite their remarkable simplicity these HC-PADs exhibit electrochemical and hydrodynamic behavior similar to that of traditional microelectrochemical devices.

We report that the oxygen binding energy of alloy-core@Pt nanoparticles can be linearly tuned by varying the alloy-core composition. Using this tuning mechanism, we are able to predict optimal compositions for different alloy-core@Pt nanoparticles. Subsequent electrochemical measurements of ORR activities of AuPd@Pt dendrimer-encapsulated nanoparticles (DENs) are in a good agreement with the theoretical prediction that the peak of activity is achieved for a 28% Au/72% Pd alloy core supporting a Pt shell. Importantly, these findings represent an unusual case of first-principles theory leading to nearly perfect agreement with experimental results.

Bimetallic PdPt dendrimer-encapsulated nanoparticles (DENs) having sizes of about 2 nm were synthesized by a homogeneous route that involved (1) formation of a Pd core, (2) deposition of a Cu shell onto the Pd core in the presence of H2 gas, and (3) galvanic exchange of Pt for the Cu shell. Under these conditions, a Pd@Pt core@shell DEN is anticipated, but detailed characterization by in-situ extended X-ray absorption fine structure (EXAFS) spectroscopy and other analytical methods indicate that the metals invert to yield a Pt-rich core with primarily Pd in the shell. The experimental findings correlate well with density functional theoretical (DFT) calculations. Theory suggests that the increased disorder associated with <~2 nm diameter nanoparticles, along with the relatively large number of edge and corner sites, drives the structural rearrangement. This type of rearrangement is not observed on larger nanoparticles or in bulk metals.

We demonstrate the hybridization-induced fluorescence detection of DNA on an origami-based paper analytical device (oPAD). The paper substrate was patterned by wax printing and controlled heating to construct hydrophilic channels and hydrophobic barriers in a three-dimensional fashion. A competitive assay was developed where the analyte, a single-stranded DNA (ssDNA), and a quencher-labeled ssDNA competed for hybridization with a fluorophore-labeled ssDNA probe. Upon hybridization of the analyte with the fluorophore-labeled ssDNA, a linear response of fluorescence vs analyte concentration was observed with an extrapolated limit of detection <5 nM and a sensitivity relative standard deviation as low as 3%. The oPAD setup was also tested against OR/AND logic gates, proving to be successful in both detection systems.

A bipolar electrode (BPE) is an electrically conductive material that promotes electrochemical reactions at its extremities (poles) even in the absence of a direct ohmic contact. More specifically, when sufficient voltage is applied to an electrolyte solution in which a BPE is immersed, the potential difference between the BPE and the solution drives oxidation and reduction reactions. Because no direct electrical connection is required to activate redox reactions, large arrays of electrodes can be controlled with just a single DC power supply or even a battery. The wireless aspect of BPEs also makes it possible to electrosynthesize and screen novel materials for a wide variety of applications. Finally, bipolar electrochemistry enables mobile electrodes, dubbed microswimmers, that are able to move freely in solution., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

We present a microfluidic paper analytical device (μPAD) that relies on flow in hollow channels, rather than through a cellulose network, to transport fluids. The flow rate in hollow channels is 7 times higher than in regular paper channels and can be conveniently controlled from 0 to several mm/s by balancing capillary and pressure forces. More importantly, the pressure of a single drop of liquid (~0.2 mbar) is sufficient to induce fast pressure-driven flow, making hollow channels suitable for point of care diagnostics. We demonstrate their utility for simple colorimetric glucose and BSA assays in which the time for liquid transport is reduced by a factor of 4 compared to normal cellulose channels.

A method for controlling enrichment, separation, and delivery of analytes into different secondary microchannels using simple microfluidic architecture is described. The approach, which is based on bipolar electrochemistry, requires only easily fabricated electrodes and a low-voltage DC power supply: no pumps or valves are necessary. Upon application of a voltage between two driving electrodes, passive bipolar electrodes (BPEs) are activated that result in formation of a local electric field gradient. This gradient leads to separation and enrichment of a pair of fluorescent analytes within a primary microfluidic channel. Subsequently, other passive BPEs can be activated to deliver the enriched tracers to separate secondary microchannels. The principles and performance underpinning the method are described.

Optical tracking of collisions between insulating microbeads and an ultramicroelectrode surface are correlated to electrochemical measurements and 3D simulations. The experiments are based on partial blocking of the electrode surface by the beads. Results obtained using these three methods provide details regarding the radial distribution of landing locations, the extent of current blockage, collision frequency, motion of beads on the electrode surface following collisions, and aggregation behavior both prior to collisions and afterward on the electrode surface.

We report electrocatalytic oxidation of formic acid using monometallic and bimetallic dendrimer-encapsulated nanoparticles (DENs). The results indicate that the Au147@Pt DENs exhibit better electrocatalytic activity and low CO formation. Theoretical calculations attribute the observed activity to the deformation of nanoparticle structure, slow dehydration of formic acid, and weak binding of CO on Au147@Pt surface. Subsequent experiments confirmed the theoretical predictions.

Here we report a method for highly reproducible chronoamperometric analysis of the contents of microdroplets. Aqueous microdroplets having volumes on the order of 1 nL and separated by a fluorocarbon solvent are generated within a microfluidic device using a T-shaped junction. The key finding is that stable and reproducible quasi-steady-state currents are observed if the electrochemical measurements are made in a narrowed segment of a microchannel. Under these conditions, the microdroplets are stretched, here by a factor of 10, leading to desirable intradroplet mass transfer characteristics. Microdroplet frequencies up to 0.67 s(-1) are accessible using this method. The quasi-steady-state currents resulting from chronoamperometric analysis of microdroplets containing 1.0 mM Ru(NH3)6(3+) have relative standard deviations of just 1.8% and 2.8% at flow rates of 30 nL min(-1) and 60 nL min(-1), respectively. Importantly, the design of the microelectrochemical device ensures direct contact between intradroplet redox molecules and the electrode surface. That is, the fluorocarbon between microdroplets does interfere with inner-sphere electrocatalytic processes such as the oxygen reduction reaction. Finite-element simulations are presented that are in accord with the experimental findings.

Here we report simultaneous screening of bimetallic electrocatalyst candidates for the oxygen reduction reaction (ORR) using bipolar electrochemistry. The analysis is carried out by dispensing different bimetallic precursor compositions onto the cathodic poles of an array of bipolar electrodes (BPEs) and then heating them in a reducing atmosphere to yield the catalyst candidates. Because BPEs do not require a direct electrical connection for activation, up to 33 electrocatalysts can be screened simultaneously by applying a voltage to the electrolyte solution in which the BPE array is immersed. The screening of the electrocatalyst candidates can be achieved in about 10 min. The current required to drive the ORR arises from oxidation of Cr microbands present at the anodic poles of the BPEs. Therefore, the most effective electrocatalysts result in oxidation (dissolution) of the most microbands, and simply counting the microbands remaining at the end of the screen provides information about the onset potential required to reduce oxygen. Here, we evaluated three Pd-M (M = Au, Co, W) bimetallic electrocatalysts. In principle, arbitrarily large libraries of electrocatalysts can be screened using this approach.

We report on real-time electrochemical detection of individual DNA hybridization events at an electrode surface. The experiment is carried out in a microelectrochemical device configured with a working electrode modified with single-stranded DNA probe molecules. When a complementary DNA strand labelled with a catalyst hybridizes to the probe, an easily detectable electrocatalytic current is observed. In the experiments reported here, the catalyst is a platinum nanoparticle and the current arises from electrocatalytic oxidation of hydrazine. Two types of current transients are observed: short bursts and longer-lived steps. At low concentrations of hydrazine, the average size of the current transients is proportional to the amount of hydrazine present, but at higher concentrations the hydrazine oxidation reaction interferes with hybridization.

We report a potentiometric method for measuring the hemoglobin A1c (HbA1c, glycated hemoglobin) concentration, hemoglobin (Hb) concentration, and percent HbA1c (%HbA1c) in human blood hemolysate. The %HbA1c is important for diagnosis and management of diabetes mellitus. Alizarin red s (ARS) is used as a redox indicator. Phenylboronic acid (PBA) binds to both ARS and HbA1c via diol-boronic acid complexation. The binding of PBA to ARS shifts its redox potential negatively. However, when HbA1c competes with ARS for PBA binding, the solution potential shifts positively. This shift is linked to the HbA1c concentration. The concentration of Hb is determined by allowing it to react with Fe(CN)(6)(3-). The potential shift arising from the reduction of Fe(CN)(6)(3-) by Hb is proportional to the logarithm of the Hb concentration. The results obtained for %HbA1c in human blood hemolysate are in good agreement with those determined using a reference method.

In this paper we show that a microelectrochemical cell comprising two parallel microchannels spanned by a single bipolar electrode can be used to simultaneously enrich and separate both anions and cations within a single microchannel. This is possible because reduction and oxidation of water at the cathodic and anodic poles of the bipolar electrode, respectively, lead to ion depletion zones. Specifically, TrisH(+) is neutralized by OH(-) at the cathodic pole, while acetate buffer is neutralized by H(+) at the anodic pole. This action creates a local electric field gradient having both positive and negative components, and hence positive and negative ions follow their respective field gradients leading to separation. In the presence of an opposing counter-flow (pressure driven flow in this case), enrichment also occurs. In addition to separation and enrichment in a single channel, it is also possible to simultaneously enrich cations in one microchannel and anions in the other. Enrichment is achieved by controlling experimental parameters, including the type of buffer and the direction and magnitude of the opposing counter-flow.

We have previously demonstrated up to 5 × 10(5)-fold enrichment of anionic analytes in a microchannel using a technique called bipolar electrode focusing (BEF). Here, we demonstrate that BEF can also be used to enrich a cationic fluorescent tracer. The important point is that chemical modification of the microchannel walls enables reversal of the electroosmotic flow (EOF), enabling cations, instead of anions, to be enriched via an electric field gradient focusing mechanism. Reversal of the EOF has significant consequences on the formation and shape of the region of the buffer solution depleted of charge carriers (depletion zone). Electric field measurements and numerical simulations are used to elucidate the factors influencing the depletion zone. This information is used to understand and control the location and shape of the depletion zone, which in turn influences the stability and concentration of the enriched band.

Here we report on the effect of the mass transfer rate (k(t)) on the oxygen reduction reaction (ORR) catalyzed by Pt dendrimer-encapsulated nanoparticles (DENs) comprised of 147 and 55 atoms (Pt(147) and Pt(55)). The experiments were carried out using a dual-electrode microelectrochemical device, which enables the study of the ORR under high k(t) conditions with simultaneous detection of H(2)O(2). At low k(t) (0.02 to 0.12 cm s(-1)) the effective number of electrons involved in ORR, n(eff), is 3.7 for Pt(147) and 3.4 for Pt(55). As k(t) is increased, the mass-transfer-limited current for the ORR becomes significantly lower than the value predicted by the Levich equation for a 4-electron process regardless of catalyst size. However, the percentage of H(2)O(2) detected remains constant, such that n(eff) barely changes over the entire k(t) range explored (0.02 cm s(-1)). This suggests that mass transfer does not affect n(eff), which has implications for the mechanism of the ORR on Pt nanoparticles. Interestingly, there is a significant difference in n(eff) for the two sizes of Pt DENs (n(eff) = 3.7 and 3.5 for Pt(147) and Pt(55), respectively) that cannot be assigned to mass transfer effects and that we therefore attribute to a particle size effect.

Paper biosensors: an origami sensor is printed on a single piece of paper, folded into a three-dimensional fluidic device, and encapsulated by thermal lamination. Aptamer is trapped in the fluidic channel, where it binds to the target and releases an enzyme to generate a signal. The device is read out using a digital multimeter., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

We report a two-channel microelectrochemical sensor that communicates between separate sensing and reporting microchannels via one or more bipolar electrodes (BPEs). Depending on the contents of each microchannel and the voltage applied across the BPE, faradaic reactions may be activated simultaneously in both channels. As presently configured, one end of the BPE is designated as the sensing pole and the other as the reporting pole. When the sensing pole is activated by a target, electrogenerated chemiluminescence (ECL) is emitted at the reporting pole. Compared to previously reported single-channel BPE sensors, the key advantage of the multichannel architecture reported here is physical separation of the ECL reporting cocktail and the solution containing the target. This prevents chemical interference between the two channels.