A gold coated polystyrene ring microarray formed by two-step patterning: construction of an advanced microelectrode for voltammetric sensing.

A two-step patterning process was developed based on nanosphere lithography and plasma etching to fabricate an array of electrodes with two different gold ring structures: the arrays of Au micro-ring electrode (Au-MRE) and Au covered with polystyrene micro-ring electrode (Au-PS-MRE). The Au-MRE structure was fabricated by etching a monolayer of polystyrene (PS) spheres on indium tin oxide (ITO) surface to generate PS rings on ITO glass. PS rings served as a mask in secondary etching for blocking an interaction of oxygen plasma and ITO surface to create a ring-patterned ITO surface. Then, the PS residue was removed and gold was deposited. The site-selective electrodeposition of gold was carried out and an array of a gold ring structure was formed on the ITO glass. The Au-PS-MRE structure was fabricated by keeping the PS residue from second etching before deposition of gold. The Au-PS-MRE microelectrode was studied by using hexacyanoferrate as an electrochemical probe where it displayed steady state current in cyclic voltammetry. The respective calibration plots were acquired at a working potential of 0.31 V and 0.12 V (vs. Ag/AgCl) for oxidation and reduction reaction, respectively. The sensitivity is as high as 163.4-220.7 µA·mM-1·mm-2 which is larger by a factor of 95-132 compared to a conventional gold film macroelectrode. The detection limit (at a signal-to-noise ratio of 3) is 2.2 µM. This approach thus yields relatively effective and low-cost fabrication without resorting to high resolution instruments. Conceivably, the technique may be used to produce microelectrode arrays on a large scale. Graphical abstract Schematic presentation of a novel fabrication process of micro-ring electrode arrays. Two-step patterning based on nanosphere lithography leads to electrodes with great electrochemical performance. Direct deposition metal in the presence of polystyrene (PS) mask induces the formation of a new structure with arrays of gold covered with PS microring on the indium tin oxide (ITO) coated glass. The microelectrode-like behavior has been achieved using this fabrication process.

Dually functional polyethylenimine-coated gold nanoparticles: a versatile material for electrode modification and highly sensitive simultaneous determination of four tumor markers.

A novel sandwich-type electrochemical multiplex immunoassay is described for simultaneous detection of the tumor biomarkers alpha fetoprotein (AFP), carcinoembryonic antigen (CEA), prostate-specific antigen (PSA) and interleukin-8 (IL-8). Polyethylenimine-coated gold nanoparticles (PEI-AuNPs) were used for both modification of a screen-printed carbon electrode (SPCE) and as labeling tags. The coated AuNPs can be easily adsorbed on the electrodes which also are loaded with the electroactive metal ions cadmium(II), lead(II) copper(II) and silver(I) and related secondary antibodies (Ab2). These give distinct voltammetric signals at -0.80, -0.55, -0.20 and + 0.05 V, respectively (vs Ag/AgCl). Four corresponding capture antibodies (Ab1) were then conjugated to one of the electrodes. After a sandwich-type structure was formed by binding of the analytes and the labeling AuNPs, the electrochemical signal responses were recorded. Under the optimized testing conditions, there is a linear relationship in range from 0.25-10 ng mL-1 for AFP, CEA and PSA, and from 0.50-100 pg mL-1 for IL-8. The corresponding detection limits are 1.7, 1.6, 0.9 and 1.0 fg mL-1, respectively. Cross reactivity, interferences and stability of the modified electrodes and of the signal nanotags are satisfying in that they can be stored for >4 weeks without significant signal reduction. The method was successfully applied to the determination of the biomarkers in spiked human serum. Graphical abstract Poly(ethylenimine)-coated gold nanoparticles were used in a sandwich-type multiplex electrochemical immunosensor. The coated gold nanoparticles were used for both electrode modification and as electrochemical nanotags. The resultingvmmunosensor exhibits excellent sensitivity for the four analytes studied, and also displays selectivity and long-term stability.

Sensitive amperometric biosensors for detection of glucose and cholesterol using a platinum/reduced graphene oxide/poly(3-aminobenzoic acid) film-modified screen-printed carbon electrode.

A facile one-step electrochemical synthesis of a platinum/reduced graphene oxide/poly(3-aminobenzoic acid) (Pt/rGO/P3ABA) nanocomposite film on a screen-printed carbon electrode (SPCE) and its application in the development of sensitive amperometric biosensors was successfully demonstrated herein. The electropolymerization of P3ABA together with co-electrodeposition of rGO and Pt was conducted by cyclic voltammetry, as was the GO reduction to rGO. A Pt/rGO/P3ABA-modified SPCE exhibited excellent electrocatalytic oxidation towards hydrogen peroxide (H2O2) and can be employed as an electrochemical platform for the immobilization of glucose oxidase (GOx) and cholesterol oxidase (ChOx) to fabricate glucose and cholesterol biosensors, respectively. Under the optimized conditions at a working potential of +0.50 V, the proposed biosensors revealed excellent linear responses to glucose and cholesterol in the concentration ranges of 0.25-6.00 mM and 0.25-4.00 mM, respectively, with high sensitivities of 22.01 and 15.94 µA mM-1 cm-2 and low detection limits (LODs) of 44.3 and 40.5 µM. Additionally, the Michaelis-Menten constant (Km) of GOx was 3.54 mM, while the Km of ChOx was 3.82 mM. Both biosensors displayed a good anti-interference ability and clearly exhibited acceptable recoveries for the detection of glucose and cholesterol in a human serum sample (98.2-104.1%).

Electrochemical detection of c-reactive protein based on anthraquinone-labeled antibody using a screen-printed graphene electrode.

In this present work, a novel electrochemical immunosensor employing a screen-printed graphene electrode (SPGE) for a simple and highly sensitive determination of C-reactive protein (CRP) in a sandwich-type format was proposed. The sensor comprised of two CRP-specific antibodies: an unlabeled capture primary antibody (Anti-1°Ab) and an electrochemically detectable anthraquinone-labeled signaling secondary (AQ-2°Ab) antibody. The Anti-1°Ab was first covalently anchored onto an L-cysteine/gold-modified disposable SPGE (L-Cys/Au/SPGE) to create the anti-CRP surface. After binding of the CRP and the AQ-2°Ab, the electrochemical signal response was measured using differential pulse voltammetry (DPV). In the presence of CRP, the sensor exhibited a significant increase in the AQ current at AQ-2°Ab compared to the negative control. The CRP concentration was detected in the range of 0.01-150 µg/mL, and the limit of detection (LOD) (S/N = 3) and limit of quantitation (LOQ) (10 SD/Slope) were 1.5 ng/mL and 10 ng/mL, respectively. This sensor exhibited very high sensitivity in determining CRP and was successfully applied to detect CRP in certified human serum with satisfactory results. The developed sensor is suitable as an alternative method for determination of CRP and the same principle may be further applied to determine other clinically important target molecules.

A sensitive electrochemical immunosensor based on poly(2-aminobenzylamine) film modified screen-printed carbon electrode for label-free detection of human immunoglobulin G.

This work focuses on fabricating poly(2-aminobenzylamine)-modified screen-printed carbon electrode as an electrochemical immunosensor for the label-free detection of human immunoglobulin G. To selectively detect immunoglobulin G, the anti-immunoglobulin G antibody with high affinity to immunoglobulin G was covalently linked with the amine group of poly(2-aminobenzylamine) film-deposited screen-printed carbon electrode. The selectivity for immunoglobulin G was subsequently assured by being challenged with redox-active interferences and adventitious adsorption did not significantly interfere the analyte signal. To obviate the use of costly secondary antibody, the [Fe(CN)6]4-/3- redox probe was instead applied to measure the number of human immunoglobulin G through the immunocomplex formation that is quantitatively related to the level of the differential pulse voltammetric current. The resulting immunosensor exhibited good sensitivity with the detection limit of 0.15 ng mL-1, limit of quantitation of 0.50 ng mL-1 and the linear range from 1.0 to 50 ng mL-1. Given those striking analytical performances and the affordability arising from using cheap screen-printed carbon electrode with label-free detection, the immunosensor serves as a promising model for the next-step development of a diagnostic tool.

Site-Selective Controlled Dealloying Process of Gold-Silver Nanowire Array: a Simple Approach towards Long-Term Stability and Sensitivity Improvement of SERS Substrate.

Limitations of achieving highly sensitive and stable surface-enhanced Raman scattering (SERS) substrate greatly concern the suitable method for fabrication of large-area plasmonic nanostructures. Herein we report a simple approach using template-based synthesis to create a highly ordered two-dimensional array of gold-silver alloy nanowires, followed by the controlled dealloying process. This particular step of mild acid etching (15%v/v nitric acid for 5 min) allowed the formation of Raman hot spots on the nanowire tips while maintaining the integrity of highly active alloy composition and rigid nanowire array structure. Full consideration of SERS substrate performance was accomplished using 4-mercaptobenzoic acid (4-MBA) as a probe molecule. Exceedingly higher SERS signal (150-fold) can be achieved with respect to typical gold film substrate. Moreover, an excellent stability of SERS substrate was also determined for over 3 months storage time. In contrast to the previous studies which stability improvement was accomplished at a cost of sensitivity reduction, the simultaneous improvement of sensitivity and stability makes the controlled dealloying process an excellent choice of SERS substrate fabrication. In addition, uniformity and reproducibility studies indicated satisfactory results with the acceptable values of relative standard deviation.

Ultrasensitive electrochemical immunosensor based on dual signal amplification process for p16(INK4a) cervical cancer detection in clinical samples.

The p16(INK4a) (p16) is a cyclin-dependent kinase inhibitor, which has been evaluated in several studies as a diagnostic marker of cervical cancer. Immunostaining using p16 specific antibody has confirmed an over-expression of p16 protein in cervical cancer cells and its association with disease progression. This article reports an ultrasensitive electrochemical immunosensor for specific detection of p16 and demonstrates its performance for detection of solubilized p16 protein in cell lysates obtained from patients. Sandwich-based immunoreaction couple with double signal amplification strategy based on catalytic enlargement of particle tag was used for high sensitivity and specificity. The conditions were optimized to create an immunoassay protocol. Disposable screen-printed electrode modified with capture antibodies (Ab1) was selected for further implementation towards point-of-care diagnostics. Small gold nanoparticles (15 nm diameter) conjugated with detection antibodies (Ab2) were found to better serve as a detection label due to limited interference with antigen-antibody interaction. Double signal enhancement was performed by sequential depositions of gold and silver layers. This gave the sensitivity of 1.78 µA mL(ng GST-p16)(-1) cm(-2) and detection limit of 1.3 ng mL(-1) for GST-p16 protein which is equivalent to 0.49 ng mL(-1) for p16 protein and 28 cells for HeLa cervical cancer cells. In addition to purified protein, the proposed immunosensor effectively detected elevated p16 level in cervical swab samples obtained from 10 patients with positive result from standard Pap smear test, indicating that an electrochemical immunosensors hold an excellent promise for detection of cervical cancer in clinical setting.

Flow-based solution-liquid-solid nanowire synthesis.

Discovered almost two decades ago, the solution-liquid-solid (SLS) method for semiconductor nanowire synthesis has proven to be an important route to high-quality, single-crystalline anisotropic nanomaterials. In execution, the SLS technique is similar to colloidal quantum-dot synthesis in that it entails the injection of chemical precursors into a hot surfactant solution, but mechanistically it is considered the solution-phase analogue to vapour-liquid-solid (VLS) growth. Both SLS and VLS methods make use of molten metal nanoparticles to catalyse the nucleation and elongation of single-crystalline nanowires. Significantly, however, the methods differ in how chemical precursors are introduced to the metal catalysts. In SLS, precursors are added in a one-off fashion in a flask, whereas in VLS they are carried by a flow of gas through the reaction chamber, and by-products are removed similarly. The ability to dynamically control the introduction of reactants and removal of by-products in VLS synthesis has enabled a degree of synthetic control not possible with SLS growth. We show here that SLS synthesis can be transformed into a continuous technique using a microfluidic reactor. The resulting flow-based SLS ('flow-SLS') platform allows us to slow down the synthesis of nanowires and capture mechanistic details concerning their growth in the solution phase, as well as synthesize technologically relevant axially heterostructured semiconductor nanowires, while maintaining the propensity of SLS for accessing ultrasmall diameters below 10 nm.

'Giant' CdSe/CdS core/shell nanocrystal quantum dots as efficient electroluminescent materials: strong influence of shell thickness on light-emitting diode performance.

We use a simple device architecture based on a poly(3,4-ethylendioxythiophene):poly(styrenesulfonate) (PEDOT:PSS)-coated indium tin oxide anode and a LiF/Al cathode to assess the effects of shell thickness on the properties of light-emitting diodes (LEDs) comprising CdSe/CdS core/shell nanocrystal quantum dots (NQDs) as the emitting layer. Specifically, we are interested in determining whether LEDs based on thick-shell nanocrystals, so-called "giant" NQDs, afford enhanced performance compared to their counterparts incorporating thin-shell systems. We observe significant improvements in device performance as a function of increasing shell thickness. While the turn-on voltage remains approximately constant for all shell thicknesses (from 4 to 16 CdS monolayers), external quantum efficiency and maximum luminance are found to be about one order of magnitude higher for thicker shell nanocrystals (≥13 CdS monolayers) compared to thinner shell structures (<9 CdS monolayers). The thickest-shell nanocrystals (16 monolayers of CdS) afforded an external quantum efficiency and luminance of 0.17% and 2000 Cd/m(2), respectively, with a remarkably low turn-on voltage of ~3.0 V.

Rapid delivery of drug carriers propelled and navigated by catalytic nanoshuttles.

This paper reports the first proof-of-concept of using catalytic nanoshuttles to pick up, transport, and release common drug carriers including biocompatible and biodegradable polymeric particles and liposomes. The rapid transport of a wide size range of drug-loaded particles (100 nm-3.0 µm) with a speed approximately three orders of magnitude faster than that of the particles transported by Brownian motion demonstrates the high propulsion power of the nanoshuttles. The nanoshuttles' navigation ability is illustrated by the transport of the drug carriers through a microchannel from the pick-up to the release microwell. Such ability of nanomotors to rapidly deliver drug-loaded polymeric particles and liposomes to their target destination represents a novel approach towards transporting drug carriers in a target-specific manner. This also potentially addresses the obstacles of current nanoparticle drug delivery, such as off-targeting of particles. While an initial concept of actively transporting therapeutic particles is demonstrated in vitro in this paper, future efforts will focus on practical in vivo motor-based targeted drug delivery in connection to fuel-free nanovehicles.

Synthetic nanomotors in microchannel networks: directional microchip motion and controlled manipulation of cargo.

We illustrate the use of catalytic nanowire motors for directional motion and microscale transport of cargo within microfluidic channel networks. The CNT-based synthetic nanomotor can propel a large cargo load at high speeds through predetermined paths and junctions of the microchannel network. The magnetic properties of the nickel-containing nanomotors offer controlled cargo manipulations, including en-route load, drag, and release. Such use of synthetic nanomachines can lead to chemically powered versatile laboratory-on-a-chip devices performing a series of tasks simultaneously or sequentially.

Carbon-nanotube-induced acceleration of catalytic nanomotors.

Synthetic nanoscale motors represent a major step toward the development of practical nanomachines. Despite impressive progress, man-made nanomachines lack the efficiency and speed of their biological counterparts. Here we show that the incorporation of carbon nanotubes (CNT) into the platinum (Pt) component of asymmetric metal nanowire motors leads to dramatically accelerated movement in hydrogen-peroxide solutions, with average speeds (50-60 microm/s) approaching those of natural biomolecular motors. Further acceleration to 94 microm/s, with some motors moving above 200 microm/sis observed upon adding hydrazine to the peroxide fuel. Factors influencing the accelerated movement, including the CNT loading and fuel concentration, are examined. Such development of highly efficient and controllable nanomotors offers great promise for self-powered nanoscale transport and delivery systems.

Adaptive nanowire-nanotube bioelectronic system for on-demand bioelectrocatalytic transformations.

An integrated nanobioelectronic system, exploiting the distinct properties of nanowires and carbon-nanotubes, has been designed for triggering reversibly and on-demand bioelectrocatalytic transformations of alcohols.

Adaptive nanowires for switchable microchip devices.

This paper demonstrates for the first time the use of adaptive functional nickel nanowires for switching on-demand operation of microfluidic devices. Controlled reversible magnetic positioning and orientation of these nanowires at the microchannel outlet offers modulation of the detection and separation processes, respectively. The former facilitates switching between active and passive detection states to allow the microchip to be periodically activated to perform a measurement and reset it to the passive ("off") state between measurements. Fine magnetic tuning of the separation process (postchannel broadening of the analyte zone) is achieved by reversibly modulating the nanowire orientation (i.e., detector alignment) at the channel outlet. The concept can be extended to other microchip functions and stimuli-responsive materials and holds great promise for regulating the operation of microfluidic devices in reaction to specific needs or unforeseen scenarios.

Shape-tailored porous gold nanowires: from nano barbells to nano step-cones.

Step-like porous gold nanowires of different shapes and diameters have been prepared by sequentially depositing alloy segments composed of different gold/silver ratios and de-alloying the silver component. For example, step-cone and nano-barbell porous gold nanowires were generated by a membrane-templated sequential deposition of gold-silver alloy segments from plating solutions of respectively decreasing or alternating gold/silver composition ratios. Alloy segments of different gold/silver ratios, prepared by using different plating potentials, also lead to multistep nanowires. In addition to step-like nanowires, we describe the preparation of cone- and bone-shaped porous nanowires from alloy nanowires of longitudinally changing compositions, generated via deposition from a flowing plating solution of a continuously changing composition. Such customization of the porous gold nanostructure is attributed to the chemical removal of silver and the different extents of gold reordering from alloy segments of different compositions. The latter leads to porous gold segments of smaller diameters from silver-rich alloy segments. The new "nanomachining" concept is versatile and could be extended to nanowires of diverse shapes with a variety of properties, generating an attractive assortment of nano-hardware.

Magnetic tuning of the electrochemical reactivity through controlled surface orientation of catalytic nanowires.

Nanowires have received considerable attention owing to their broad potential applications. We report here on the application of nanowires for magnetic control of the electrochemical reactivity and demonstrate how one can modulate the electrocatalytic activity by orienting catalytic nanowires at different angles. Unlike early "on/off" magnetic switching studies based on functionalized magnetic spheres, the present magnetoswitchable protocol relies on modulating the electrochemical reactivity without removing the magnetic material from the surface. Such behavior is attributed to the reversible blocking of the redox processes and to changes in the tortuosity-dependent flux rate. The nanowire-based magnetoswitchable protocol may be extremely useful for adjusting the electrochemical reactivity, such as for tuning the power output of fuel cells (rather than switching the power on/off).

Microchip capillary electrophoresis/electrochemical detection of hydrazine compounds at a cobalt phthalocyanine modified electrochemical detector.

This article reports on the use of cobalt(II) phthalocyanine (CoPc)-modified carbon paste amperometric detector for monitoring hydrazine compounds following their microchip separation. The marked catalytic electrochemical properties of CoPc-modified electrode display enhanced sensitivity compared with unmodified carbon pastes at a relatively low detection potential (+0.5V versus Ag/AgCl). Factors influencing the on-chip separation and detection processes have been optimized. Three hydrazines (hydrazine, 1,1 dimethylhydrazine, and phenylhydrazine) have been separated within 130s at a separation voltage of 1kV using a 10mM phosphate run buffer (pH 6.5). The detection limits obtained from using the CoPc-modified carbon paste electrodes for hydrazine and phenylhydrazine are 0.5 and 0.7muM, respectively, with linearity over the 20-200muM range examined. Such miniaturization and speed advantages of microchip CE are coupled to the highly sensitivity and convenient preparation of CoPc-modified carbon paste electrode. The resulting microsystem should be attractive for field monitoring of toxic hydrazine compounds in environmental applications.