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In this work we present the results obtained on the simulation and nanofabrication of photonic crystals based on silicon nanopillars. The simulations show the formation of photonic band gaps within 1.31 and 1.89μm, with a gap-to-midgap ratio approaching 40%. The introduction of waveguides and cavities prove the adaptability of these structures to tune the wavelengths allowed to be transmitted through the system within the photonic band gaps. On the other hand, thanks to the use of advanced nanofabrication techniques, the modelled structures have been successfully fabricated.

In this work we have explored the use of a Surface Plasmon resonance (SPR) phenomenon for the detection of interleukin-6 (IL-6), a pro-inflammatory cytokine. It plays an important role in the muscle tissues, having direct relation with muscle contraction and, thus, it is considered a biomarker for some types of muscular dystrophies. Here we show that SPR can be used as a real-time monitoring of the shift of the reflectance dip of a gold diffraction grating in front to the antibody adhesion to gold.

Bacteria detection, counting and analysis is of great importance in several fields. When viability plays a major role in decision making, the counting of colony-forming units grown on agar plates remains the gold standard. However, because plate counts depend on the growth of the bacteria, it is a slow procedure and only works with culturable species. Impedance flow cytometry (IFC) is a promising technology for particle detection, counting and characterization. It relies on the perturbation of an electric field by particles flowing through a microfluidic channel. The perturbation is directly related to the electrical properties of the particles, and therefore provides information about their composition and structure. In this work we investigate whether IFC can be used to differentiate viable cells from inactivated cells. Our findings demonstrate that the specific viability state of the bacteria has to be considered, but that with proper characterization thresholds, IFC can be used to classify bacterial viability states. By using three different inactivation methods&mdash, ethanol, heat and autoclavation&mdash, we have been able to show that the impedance response of Escherichia coli depends on its viability state, but that the specific response depends on the inactivation method. With these findings we expect to be able to optimize IFC for more reliable bacteria detection and counting in the future.

Primary brain cells cultured on flat surfaces, i.e., in a two-dimensional fashion, have a long history of use as an experimental model system in neuroscience research. However, it is questionable to which extent these cultured brain cells resemble their in vivo counterparts. Mainly, it has been claimed that the non-oxidative glucose metabolism reflected by lactate production is unphysiologically high. Furthermore, it is known that culturing in 2D alters the phenotype of cells. Here we present diphenylalanine peptide nanowires (PNWs) as a culturing substrate for primary neocortical neurons from mice. The topology of the PNWs leads to neuronal cultures developing in 2.5D environment and hence improved culturing conditions. We investigate the effect of different concentrations of PNWs and different cell densities of neurons on the culturing conditions. The neocortical neurons were examined through scanning electron microscopy in order to study the effect of PNW concentrations and neuron densities on the structural appearance of the cells. Then employing the optimal combination of neuron density and PNW concentration, the neurons were evaluated functionally and metabolically by comparison with neocortical neurons standard culturing methods in 2D. Specifically, we tested neuronal viability, capacity for vesicular release of neurotransmitter GABA, as well as oxidative and non-oxidative glucose metabolism. It was evident that neurons cultured on PNWs exhibited increased viability combined with an increased capacity for neurotransmitter release and a lower fraction of non-oxidative metabolism than neurons cultured in 2D. Hence, neocortical neurons cultured in 2.5D on PNWs appear to be healthier and less glycolytic than neurons cultured in 2D.

Pseudomonas aeruginosa (PA) is a pathogen that is recognized for its advanced antibiotic resistance and its association with serious diseases such as ventilator-associated pneumonia and cystic fibrosis. The ability to rapidly detect the presence of pathogenic bacteria in patient samples is crucial for the immediate eradication of the infection. Pyocyanin is one of PA’s virulence factors used to establish infections. Pyocyanin promotes virulence by interfering in numerous cellular functions in host cells due to its redox-activity. Fortunately, the redox-active nature of pyocyanin makes it ideal for detection with simple electrochemical techniques without sample pretreatment or sensor functionalization. The previous decade has seen an increased interest in the electrochemical detection of pyocyanin either as an indicator of the presence of PA in samples or as a tool for quantifying PA virulence. This review provides the first overview of the advances in electrochemical detection of pyocyanin and offers an input regarding the future directions in the field.

Bentazone is one of the most problematic pesticides polluting groundwater resources. It is on the list of pesticides that are mandatory to analyze at water work controls. The current pesticide measuring approach includes manual water sampling and time-consuming chromatographical quantification of the bentazone content at centralized laboratories. Here, we report the use of an electrochemical approach for analytical determination of bentazone that takes 10 s. The electrochemical electrodes were manually screen printed, resulting in the low-cost fabrication of the sensors. The current response was linearly proportional to the bentazone concentration with a R2 ~ 0.999. We demonstrated a sensitivity of 0.0987 μA/μM and a limit of detection of 0.034 μM, which is below the U.S. Health Advisory level. Furthermore, the sensors have proved to be reusable and stable with a drop of only 2% after 15 times reuse. The sensors have been applied to successfully quantify bentazone spiked in real groundwater and lake water. The sensing method presented here is a step towards on-site application of electrochemical detection of pesticides in water sources. Keywords: Bentazone, Sensor, Groundwater, Electrochemistry, Pesticide, Contamination

Pyocyanin is a virulence factor solely produced by the pathogen Pseudomonas aeruginosa. Pyocyanin is also a redox active molecule that can be directly detected by electrochemical sensing. A nanograss (NG) based sensor for sensitive quantification of pyocyanin in sputum samples from cystic fibrosis (CF) patients is presented here. The NG sensors were custom made in a cleanroom environment by etching nanograss topography on the electrode surface followed by depositing 200 nm gold. The NG sensors were utilized for amperometric quantification of pyocyanin in spiked hypertonic saline samples, resulting in a linear calibration curve with a R2 value of 0.9901 and a limit of detection of 172 nM. The NG sensors were applied in a small pilot test on five airway samples from five CF patients. The NG sensor was capable of identifying P. aeruginosa in the airway samples in 60 s without any sample pretreatment.

Glyphosate (Gly) is one of the most problematic pesticides that repeatedly appears in drinking water. Continuous on-site detection of Gly in water supplies can provide an early warning in incidents of contamination, before the pesticide reaches the drinking water. Here, we report the first direct detection of Gly in tap water with electrochemical sensing. Gold working electrodes were used to detect the pesticide in spiked tap water without any supporting electrolyte, sample pretreatment or electrode modifications. Amperometric measurements were used to quantify Gly to a limit of detection of 2 &mu, M, which is below the regulation limit of permitted contamination of drinking water in the United States. The quantification of Gly was linearly proportional with the measured signal. The selectivity of this method was evaluated by applying the same technique on a Gly Metabolite, AMPA, and on another pesticide, omethoate, with a chemical structure similar to Gly. The testing revealed no interfering electrochemical activity at the potential range used for Gly detection. The simple detection of Gly presented in this work may lead to direct on-site monitoring of Gly contamination at drinking water sources.

Candidemia and invasive candidiasis is a cause of high mortality and morbidity rates among hospitalized patients worldwide. The occurrence of the infections increases due to the complexity of the patients and overuse of the antifungal therapy. The current Candida detection method includes blood culturing which is a lengthy procedure and thus delays the administration of the antifungal therapy. Even though the results are available after 48 h it is still the gold standard in pathogen detection in a hospital setting. In this work we present an electrochemical impedance sensor that is capable of detecting Candida albicans yeast. The yeast cells are captured on electrodes specifically functionalized with anti-Candida antibodies and detection is achieved by electrochemical impedance spectroscopy. The sensor allows for detection of the yeast cells at clinically relevant concentrations in less than 1 h.

Based on a modified version of standard chips for fast differential scanning calorimetry, DSC of liquid samples has been performed at temperature scan rates of up to 1000 °C/s. This paper describes experimental results with the protein lysozyme, bovine serum, and olive oil. The heating and cooling rate of the sensor is measured for temperature scan rates of up to 1300 °C/s with water and 2-butanol, in the temperature range of −90 °C/s to +130 °C/s. The lysozyme is measured at temperature scan rates varying from 10 °C/s to 400 °C/s and in concentrations between 0.1% and 10% protein by weight. The bovine serum measurements show two main peaks, in good agreement with standard DSC measurements. Olive oil has been measured, with good agreement for the cooling curve and qualitative agreement for the heater curve, compared to DSC measurements.

This article presents a novel membrane-based sensor for real-time electrochemical investigations of cellular- or tissue cultures. The membrane sensor enables recording of electrical signals from a cell culture without any signal dilution, thus avoiding loss of sensitivity. Moreover, the porosity of the membrane provides optimal culturing conditions similar to existing culturing techniques allowing more efficient nutrient uptake and molecule release. The patterned sensor electrodes were fabricated on a porous membrane by electron-beam evaporation. The electrochemical performance of the membrane electrodes was characterized by cyclic voltammetry and chronoamperometry, and the detection of synthetic dopamine was demonstrated down to a concentration of 3.1 pM. Furthermore, to present the membrane-sensor functionality the dopamine release from cultured PC12 cells was successfully measured. The PC12 cells culturing experiments showed that the membrane-sensor was suitable as a cell culturing substrate for bio-applications. Real-time measurements of dopamine exocytosis in cell cultures were performed, where the transmitter release was recorded at the point of release. The developed membrane-sensor provides a new functionality to the standard culturing methods, enabling sensitive continuous in vitro monitoring and closely mimicking the in vivo conditions.

A modified and improved photografting procedure of Topas® surface hydrophilization is investigated in order to obtain stable modification of the polymer for long term storage. The achieved hydrophilicity and monitoring of the wettability during one month of storage are presented as well as a description of the optimal cleaning procedure and storage conditions to maintain the modified surface. Three minutes of oxygen plasma activation followed by 4 min of acrylic acid UV-photografting at 50 °C leads to the most stable hydrophilicity that was characterized by an initial water contact angle of 53.5° ± 1.2°. Storage of the modified material in cold water at 4 °C and refraining from ultrasonic cleaning limit water contact angle increase to 5° over 30 days. In comparison with pristine hydrophobic Topas, the proposed treatment improves chromosome spreading ability significantly.

A new method for measuring specific protein concentrations in solutions has been developed. The technique makes use of the Coulter effect for detecting and sizing of micro-scaled objects suspended in a buffer fluid. The method is completely label-free as it is only based on the electrical readout when a suspension of microscopic beads flows over a set of electrodes in a microfluidic device. Since no electrode functionalization is needed the same device can be used in a number of different assays. Using goat-anti-rat IgG functionalized polystyrene beads we have shown proof of principle detecting rat IgG in solution. When the analyte (rat IgG) is present oligomers of beads are formed. The electrical readout of the oligomers is different compared to a zero control sample with no rat IgG. Detection of the protein has been performed in a concentration as small as 14 ng/mL. The dynamic range of the system has been demonstrated to be relatively large, ranging from 1 μg/mL to 14 ng/mL. The microfluidic system is made from polymer and glass and very little volume of sample (

Downscaling of microfluidic cell culture and detection devices for electrochemical monitoring has mostly focused on miniaturization of the microfluidic chips which are often designed for specific applications and therefore lack functional flexibility. We present a compact microfluidic cell culture and electrochemical analysis platform with in-built fluid handling and detection, enabling complete cell based assays comprising on-line electrode cleaning, sterilization, surface functionalization, cell seeding, cultivationand electrochemical real-time monitoring of cellular dynamics. To demonstrate the versatility and multifunctionality of the platform, we explored amperometric monitoring of intracellular redox activity in yeast (Saccharomyces cerevisiae) and detection of exocytotically released dopamine from rat pheochromocytoma cells (PC12). Electrochemical impedance spectroscopy was used in bothapplications for monitoring cell sedimentation and adhesion as well as proliferation in the case of PC12 cells. The influence of flow rate on the signal amplitude in the detection of redox metabolism as well as the effect of mechanical stimulation on dopamine release were demonstrated using the programmable fluid handling capability. The here presented platform is aimed at applications utilizing cell based assays, ranging from e.g. monitoring of drug effects in pharmacological studies, characterization of neural stem cell differentiation, and screening of genetically modified microorganisms to environmental monitoring.

Protein nanofibrils and nanotubes are now widely accepted as having potential for use in the field of bionanotechnology. For this to be a feasible alternative to existing technologies, there is a need for a commercially viable source. Previous work has identified amyloid fibrils formed from crude crystallin proteins as such a source, since these fibrils can be produced in large quantities at a low cost. Applications include use of fibrils as templates for the formation of nanowires or as biosensing scaffolds. There remains a number of practical considerations, such as stability and the ability to control their arrangement. In this study, crude crystallin amyloid fibrils are shown to be stable in a range of biological and clean room solvents, with the fibril presence confirmed by transmission electron microscopy and the thioflavin T fluorescent assay. The fibrils were also immobilised between microelectrodes using dielectrophoresis, which enabled the recording of I-V curves for small numbers of fibrils. This investigation showed the fibrils to have low conductivity, with current values in the range of 10(-10) A recorded. This low conductivity could be increased through modification, or alternately, the fibrils could be used unmodified for applications where they can act as templates or high surface area nanoscaffolds.

This Letter involved the preparation of a conjugate between single-walled carbon nanotubes and folic acid that was obtained without covalent chemical functionalization using a simple ‘one pot’ synthesis method. Subsequently, the conjugate was investigated by a computational hybrid method: our own N-layered Integrated Molecular Orbital and Molecular Mechanics (B3LYP(6–31G(d):UFF)). The results confirmed that the interaction occurred via hydrogen bonding between protons of the glutamic moiety from folic acid and π electrons from the carbon nanotubes. The single-walled carbon nanotube-folic acid conjugate presented herein is believed to lead the way to new potential applications as carbon nanotube-based drug delivery systems.

Aim: Pseudomonas aeruginosa is a pathogen that is prevalent in serious infections in compromised patients worldwide. A unique virulence factor of this bacterium is the redox-active molecule pyocyanin, which is a potential biomarker for the identification of P. aeruginosa infections. Here we report a direct, selective and rapid detection technique of pyocyanin. Materials & methods: Pyocyanin was detected by amperometry at a relatively high potential where the pyocyanin signal was unaffected by background contributions. Results & conclusion: Pyocyanin was detected at concentrations down to 125 nM in a 50 µM mixture of interfering compounds with a reproducibility of r2 = 0.999 (n = 5) within 200 s. The results document a step toward a point-of-care technique for diagnosis of P. aeruginosa infections.

Pyocyanin is a virulence factor uniquely produced by the pathogen Pseudomonas aeruginosa. The fast and selective detection of pyocyanin in clinical samples can reveal important information about the presence of this microorganism in patients. Electrochemical sensing of the redox-active pyocyanin is a route to directly quantify pyocyanin in real time and in situ in hospitals and clinics. The selective quantification of pyocyanin is, however, limited by other redox-active compounds existing in human fluids and by other metabolites produced by pathogenic bacteria. Here we present a direct selective method to detect pyocyanin in a complex electroactive environment using commercially available electrodes. It is shown that cyclic voltammetry measurements between –1.0 V to 1.0 V reveal a potential detection window of pyocyanin of 0.58–0.82 V that is unaffected by other redox-active interferents. The linear quantification of pyocyanin has an R2 value of 0.991 across the clinically relevant concentration range of 2–100 ηM. The proposed method was tested on human saliva showing a standard deviation of 2.5% ±1% (n = 5) from the known added pyocyanin concentration to the samples. This inexpensive procedure is suggested for clinical use in monitoring the presence and state of P. aeruginosa infection in patients.

A conjugate between single-walled carbon nanotubes, chitosan and folic acid has been prepared. It was characterized by diffusion ordered two-dimensional hydrogen-1 nuclear magnetic resonance and hydrogen-1 nuclear magnetic resonance spectroscopy which revealed the presence of a conjugate that was generated by the linkage between the carboxyl moiety of the folic acid and the amino group of the chitosan, which in turn was non-covalently bound to the single-walled carbon nanotubes. The obtained diffusion coefficient values demonstrated that free folic acid diffused more rapidly than the folic acid conjugated to single-walled carbon nanotubes–chitosan. The values of the proton signal of hydrogen-1 nuclear magnetic resonance spectroscopy and two-dimensional hydrogen-1 nuclear magnetic resonance spectroscopy further confirmed that the folic acid was conjugated to the chitosan, wrapping the single-walled carbon nanotubes.

This study describes an integrated micro ''factory'' for the preparation of biological self-assembled peptide nanotubes and nanoparticles on a polymer chip, yielding controlled growth conditions. Self-assembled peptides constitute attractive building blocks for the fabrication of biological nanostructures due to the mild conditions of their synthesis process. This biological material can form nanostructures in a rapid way and the synthesis method is less expensive as compared to that of carbon nanotubes or silicon nanowires. The present article thus reports on the on-chip fabrication of self-assembled peptide nanostructures by means of a microfluidic device that is able to resist the harsh conditions imposed by the solvent used during the nanostructure synthesis. This on-chip fabrication was found to be simple, rapid, and convenient.

Microfluidic bioreactors (μBR) are becoming increasingly popular for cell culture, sample preparation and analysis in case of routine genetic and clinical diagnostics. We present a novel μBR for non-adherent cells designed to mimic in vivo perfusion of cells based on diffusion of media through a sandwiched membrane. The culture chamber and perfusion chamber are separated by a sandwiched membrane and each chamber has separate inlet/outlets for easy loading/unloading of cells and perfusion of the media. The perfusion of media and exchange of nutrients occur through the sandwiched membrane, which was also verified with simulations. Finally, we present the application of this device for cytogenetic sample preparation, whereby we culture and arrest peripheral T-lymphocytes in metaphase and later fix them in the μBR. The expansion of T-lymphocytes from an unknown patient sample was quantified by means of CFSE staining and subsequent counting in a flow cytometer. To conclude on the applicability of μBR for genetic diagnostics, we prepare chromosome spreads on glass slides from the cultured samples, which is the primary step for metaphase FISH analysis.

The development of new drug therapies relies on studies of cell transmigration in in vitro systems. Migration has traditionally been studied using two methods, the Boyden chamber and a shear flow chamber assay. Though, commonly applied in cell transmigration studies, they are far from imitating a natural migration process. Here we describe a novel in vitro cell transmigration microfluidic assay, which mimicks physiological shear flow conditions in blood vessels. The device was designed to incorporate the principles of both the Boyden chamber and the shear flow chamber assay, i.e. migration through the membrane under flow conditions. The 3D environment of migrating cells is imitated by injecting cell adhesion proteins to coat the membrane in the device. We tested the developed device with Jurkat cells migration towards medium supplemented with serum, and with chemokine induced lymphocytes migration. The applied continuous flow of cell suspension and chemoattractant ensures that the concentration gradient is maintained in time and space. The cell adhesion proteins used to enhance cell migration in the device were fibronectin and VCAM-1. We successfully observed a multistep transmigration process by means of the developed microfluidic migration assay. The presented device is inexpensive, easy to fabricate and disposable, having a potential to be applied in basic research as well as in the drug development process.

This study has evaluated self-assembled peptide nanotubes (PNTS) and nanowires (PNWS) as etching mask materials for the rapid and low-cost fabrication of silicon wires using reactive ion etching (RIE). The self-assembled peptide structures were fabricated under mild conditions and positioned on clean silicon wafers, after which these biological nanostructures were exposed to an RIE etching process. Following this treatment, the structure of the remaining nanotubes and nanowires was analyzed by scanning electron microscopy (SEM). Important differences in the behavior of the nanotubes and the nanowires were observed after the RIE process. The nanotubes remained intact while the nanowires were destroyed by the RIE process. The instability of the peptide nanowires during this process was further confirmed with focused ion beam milling experiments. The PNTS could stand energetic argon ions for around 32 s while the PNWS resisted only 4 s before becoming milled. Based on these results, self-assembled PNTS were further used as an etching mask to fabricate silicon wires in a rapid and low-cost manner. The obtained silicon wires were subjected to structural and electrical characterization by SEM and I–V measurements. Additionally, the fabricated silicon structures were functionalized with fluorescent molecules via a biotin–streptavidin interaction in order to probe their potential in the development of biosensing devices.

Over the last couple of years, self-organizing nanotubes based on the dipeptide diphenylalanine have received much attention, mainly as possible building blocks for the next generation of biosensors and as drug delivery systems. One of the main reasons for this large interest is that these peptide nanotubes are believed to be very stable both thermally and chemically. Previously, the chemical and thermal stability of self-organizing structures has been investigated after the evaporation of the solvent. However, it was recently discovered that the stability of the structures differed significantly when the tubes were in solution. It has been shown that, in solution, the peptide nanotubes can easily be dissolved in several solvents including water. It is therefore of critical importance that the stability of the nanotubes in solution and not after solvent evaporation be investigated prior to applications in which the nanotube will be submerged in liquid. The present article reports results demonstrating the instability and suggests a possible approach to a stabilization procedure, which drastically improves the stability of the formed structures. The results presented herein provide new information regarding the stability of self-organizing diphenylalanine nanotubes in solution.

Conducting polymer 3D microelectrodes have been fabricated for possible future neurological applications. A combination of micro-fabrication techniques and chemical polymerization methods has been used to create pillar electrodes in polyaniline and polypyrrole. The thin polymer films obtained showed uniformity and good adhesion to both horizontal and vertical surfaces. Electrodes in combination with metal/conducting polymer materials have been characterized by cyclic voltammetry and the presence of the conducting polymer film has shown to increase the electrochemical activity when compared with electrodes coated with only metal. An electrochemical characterization of gold/polypyrrole electrodes showed exceptional electrochemical behavior and activity. PC12 cells were finally cultured on the investigated materials as a preliminary biocompatibility assessment. These results show that the described electrodes are possibly suitable for future in-vitro neurological measurements.

Pyocyanin is a toxin produced by Pseudomonas aeruginosa. Here we describe a novel paper-based electrochemical sensor for pyocyanin detection, manufactured with a simple and inexpensive approach based on electrode printing on paper. The resulting sensors constitute an effective electrochemical method to quantify pyocyanin in bacterial cultures without the conventional time consuming pretreatment of the samples. The electrochemical properties of the paper-based sensors were evaluated by ferri/ferrocyanide as a redox mediator, and showed reliable sensing performance. The paper-based sensors readily allow for the determination of pyocyanin in bacterial cultures with high reproducibility, achieving a limit of detection of 95 nM and a sensitivity of 4.30 μA/μM in standard culture media. Compared to the similar commercial ceramic based sensors, it is a 2.3-fold enhanced performance. The simple in-house fabrication of sensors for pyocyanin quantification allows researchers to understand in vitro adaptation of P. aeruginosa infections via rapid screenings of bacterial cultures that otherwise are expensive and time-consuming.

We have developed a simple method for the improved release of embossed poly(methyl methacrylate) (PMMA) as well as casted poly(dimethyl siloxane) (PDMS) from a SU-8 mold using vapor phase deposition of 1H,1H,2H,2H-Perfluorodecyltrichlorosilane (FDTS). We have further investigated if prior breakage of the epoxy groups by oxygen plasma or sulfuric acid improves the deposition of FDTS. The deposition of FDTS on acid-activated and untreated SU-8 gave an identical well performing anti-stiction coating, as opposed to oxygen plasma activated surface which resulted in a poor FDTS coverage. In this paper the method for the mold fabrication as well as the vapor phase deposition of FDTS onto the mold is described; examples of released final devices using this method in PMMA and PDMS are presented.

Biological self-assembled structures are receiving increasing focus within micro- and nanotechnology, for example, as sensing devices, due to the fact that they are cheap to produce and easy to functionalize. Therefore, methods for the characterization of these structures are much needed. In this paper, electrostatic force microscopy (EFM) was used to distinguish between hollow nanotubes formed by self-assembly by a simple aromatic dipeptide, L-phenylalanine, silver-filled peptide-based nanotubes, and silver wires placed on prefabricated SiO2 surfaces with a backgate. The investigation shows that it is possible to distinguish between these three types of structures using this method. Further, an agreement between the detected signal and the structure of the hollow peptide was demonstrated; however only qualitative agreement with the mathematical expressing of the tubes is shown.

Carbon nanotube networks were assembled by dielectrophoresis on microelectrodes and their response to temperature was monitored. The stability of the networks was investigated in order to determine their suitability for use as electrical components or sensors. Our results suggest that the networks cannot readily be used for these applications since their behaviour depends greatly on the amount of oxygen adsorbed on their surfaces.

In this paper we demonstrate a novel culturing system for brain slices and neuronal cells, which can control the concentration of nutrients and the waste removal from the culture by adjusting the fluid flow within the device. The entire system can be placed in an incubator. The system has been tested successfully with brain slices and PC12 cells. The culture substrate can be modified using metal electrodes and/or nanostructures for conducting electrical measurements while culturing and for better mimicking the in vivo conditions.

Here we present a robust, stable and low-noise experimental set-up for performing electrochemical detection on a centrifugal microfluidic platform. By using a low-noise electronic component (electrical slip-ring) it is possible to achieve continuous, on-line monitoring of electrochemical experiments, even when the microfluidic disc is spinning at high velocities. Automated sample handling is achieved by designing a microfluidic system to release analyte sequentially, utilizing on-disc passive valving. In addition, the microfluidic system is designed to trap and keep the liquid sample stationary during analysis. In this way it is possible to perform cyclic voltammetry (CV) measurements at varying spin speeds, without altering the electrochemical response. This greatly simplifies the interpretation and quantification of data. Finally, real-time and continuous monitoring of an entire electrochemical experiment, including all intermediate sample handling steps, is demonstrated by amperometric detection of on-disc mixing of analytes (PBS and ferricyanide).

The presented microfluidic interconnection system provides an alternative for the individual interfacing of simple microfluidic devices fabricated in polymers such as polymethylmethacrylate, polycarbonate and cyclic olefin polymer. A modification of the device inlet enables the direct attachment of tubing (such as polytetrafluoroethylene tubing) secured and sealed by using a small plug, without the need for additional assembly, glue or o-rings. This provides a very clean connection that does not require additional, potentially incompatible, materials. The tightly sealed connection can withstand pressures above 250 psi and therefore supports applications with high flow rates or highly viscous fluids. The ease of incorporation, configuration, fabrication and use make this interconnection system ideal for the rapid prototyping of simple microfluidic devices or other integrated systems that require microfluidic interfaces. It provides a valuable addition to the toolbox of individual and small arrays of connectors suitable for micromachined or template-based injection molded devices since it does not require protruding, threaded or glued modifications on the inlet and avoids bulky and expensive fittings.

The resonance frequency and the Q-factor of the fundamental and higher order flexural modes of silicon dioxide microcantilevers have been characterized at different pressures and for different thicknesses of gold coating. We present the experimental results and discuss the effect of the gold film on the performance and sensitivity of the cantilevers when used as mass sensors. An almost linear relationship between the Q-factor and the resonance frequency of the uncoated cantilevers is observed, implying that a higher sensitivity can be attained by actuation at higher order resonant modes. We also find that even a thin gold coating may reduce Q-factors by more than an order of magnitude.

The resonance frequency of the fundamental and four higher order modes of a silicon dioxide microcantilever is measured. The effect on these modes of depositing a 400 nm gold coating is investigated theoretically and experimentally. We derive an analytical solution to the eigenmodes of a multi-layered cantilever and verify its validity by comparison to finite-element analysis as well as the experimentally obtained results. The temperature and pressure dependence of the resonance frequencies is investigated experimentally and found to be in good agreement with theoretical models. An experimentally obtained value for the temperature dependence of Young's modulus of elasticity for thermally grown SiO2 is presented.

Silicon-rich nitride, deposited by LPCVD, is a low stress amorphous material with a high refractive index. After deposition the silicon-rich nitride thin film is annealed at temperatures above 1100 °C to break N H bonds, which have absorption peaks in the wavelength band important for optical telecommunication. However, silicon clustering appears in the thin films when annealing above 1150 °C. Clustering is undesirable in waveguide materials because the localized variations of the refractive index associated with the clusters lead to Raleigh scattering, which can cause significant propagation loss in optical waveguides. This means that the annealing temperature must be high enough to break the N H bonds, but no so high as to produce clusters. Therefore, the process window for an annealing step lies between 1100 and 1150 °C. The chemical composition of amorphous silicon-rich nitride has been investigated by Rutherford back scattering (RBS) and X-ray photoelectron spectroscopy (XPS). The influence of deposition parameters and annealing temperatures on the stoichiometry and the chemical bonds will be discussed. The origin of the clusters has been found to be silicon due to severe silicon out-diffusion from the substrate during annealing at temperatures above 1100 °C.

We present results of a range of experiments of sputtering of water ice together with a guide to the literature. We studied how sputtering depends on the projectile energy and fluence, ice growth temperature, irradiation temperature and external electric fields. We observed luminescence from the decay of H(2p) atoms sputtered by heavy ion impact, but not bulk ice luminescence. Radiolyzed ice does not sputter under 3.7 eV laser irradiation. Fil: Baragiola, Raul Antonio. University of Virginia; Estados Unidos Fil: Vidal, Ricardo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina Fil: Svendsen, W.. University Of Virginia. Departament Of Materials Science.; Estados Unidos Fil: Schou, J.. University of Virginia; Estados Unidos Fil: Shi, M.. University of Virginia; Estados Unidos Fil: Bahr, D.A.. University of Virginia; Estados Unidos Fil: Atteberry, C.L.. University of Virginia; Estados Unidos

Herein, we describe the synthesis and characterization of a covalent nanoscale assembly formed between diphenylalanine micro/nanotubes (PNT) and folic acid (FA). The conjugate was obtained via chemical functionalization through coupling of amine groups of PNTs and carboxylic groups of FA. The surface analysis of PNT-FA indicated the presence of FA aggregates on the surface of PNTs. The covalent interaction between FA and self-assembled PNTs was further investigated using fluorescence microscopy, Raman and surface-enhanced Raman scattering (SERS) spectroscopies. The SERS experiments were performed on a large area silver-capped (diameter of 62 nm) silicon nanopillars with an approximate height of 400 nm and a width of 200 nm. The results showed that the PNT-FA synthesis procedure preserves the molecular structure of FA. The PNT-FA conjugate presented in this study is a promising candidate for applications in the detection and diagnosis of cancer or tropical diseases such as leishmaniasis and as a carrier nanosystem delivering drugs to malignant tumors that overexpress folate receptors.

This work describes the electrical investigation of paclitaxel-treated HeLa cells using a custom-made microfluidic biosensor for whole cell analysis in continuous flow. We apply the method of differential electrical impedance spectroscopy to treated HeLa cells in order to elucidate the changes in electrical properties compared with non-treated cells. We found that our microfluidic system was able to distinguish between treated and non-treated cells. Furthermore, we utilize a model for electrical impedance spectroscopy in order to perform a theoretical study to clarify our results. This study focuses on investigating the changes in the electrical properties of the cell membrane caused by the effect of paclitaxel. We observe good agreement between the model and the obtained results. This establishes the proof-of-concept for the application in cell drug therapy.

Sputtering of the solid hydrogens by electrons and ions exhibits features that may be related to quantum properties of these solids, i.e. a drastic enhancement of the yield for electron–bombarded thick deuterium films and a thermal peak at low ejection energies in the energy distribution of the sputtered particles.

This Article presents the development of a combined cell culture–biosensing platform using vertically aligned self-assembled peptide nanofibers. Peptide nanofibers were patterned on a microchip containing gold microelectrodes to provide the cells with a 3D environment enabling them to grow and proliferate. Gold microelectrodes were functionalized with conductive polymers for the electrochemical detection of dopamine released from PC12 cells. The combined cell culture–biosensing platform assured a close proximity of the release site, the cells and the active surface of the sensor, thereby rendering it possible to avoid a loss of sensitivity because of the diffusion of the sample. The obtained results showed that the peptide nanofibers were suitable as a cell culturing substrate for PC12 cells. The peptide nanofibers could be employed as an alternative biological material to increase the adherence properties of PC12 cells. Dopamine was amperometrically detected at a value of 168 fmole.

The deposition rate for laser ablated metals has been studied in a standard geometry for fluences up to 20J/cm2. The rate for silver and nickel is a few percent of a monolayer per pulse at the laser wavelengths 532 nm and 355 nm. The rate for nickel is significantly higher than that for silver at 532 nm, whereas the rate for the two metals is similar at 355 nm. This behaviour disagrees with calculations based on the thermal properties at low intensities as well as predictions based on formation of an absorbing plasma at high intensities. The deposition rate falls strongly with increasing pressure of the ambient gases, nitrogen and argon.

The deposition rate of laser-ablated silver has been determined for fluences between 0.5 and 15 J / cm 2 at the wavelengths 532 and 355 nm for a beam spot area of around 0.01 cm 2 . The ablated metal was collected on a quartz crystal microbalance. The rate at 5 J / cm 2 was about 4 x 10 13 Ag / cm 2 per pulse for 532 nm, and somewhat lower for 355 nm. The initial vaporization during the ablation has been studied numerically as well.

This article describes the preparation of a graphene electrode modified with a new conjugate of peptide nanotubes and folic acid for the selective detection of human cervical cancer cells over-expressing folate receptors. The functionalization of peptide nanotubes with folic acid was confirmed by fluorescence microscopy and atomic force microscopy. The peptide nanotube-folic acid modified graphene electrode was characterized by scanning electron microscopy and cyclic voltammetry. The modification of the graphene electrode with peptide nanotube-folic acid led to an increase in the current signal. The human cervical cancer cells were bound to the modified electrode through the folic acid-folate receptor interaction. Cyclic voltammograms in the presence of [Fe(CN)(6)](3-/4-) as a redox species demonstrated that the binding of the folate receptor from human cervical cancer cells to the peptide nanotube-folic acid modified electrode lowered the electron transfer resulting in a decrease in the measured current. A detection limit of 250 human cervical cancer cells per mL was obtained. Control experiments confirmed that the peptide nanotube-folic acid electrode specifically recognized folate receptors. The modified electrode described here opens up new possibilities for future applications in early stage diagnoses of diseases where cells over-express folate receptors, such as in cancer or leishmaniasis disease.

In this paper we present a series of experiments showing that vertical self-assembled diphenylalanine peptide nanowires (PNWs) are a suitable candidate material for cellular biosensing. We grew HeLa and PC12 cells onto PNW modified gold surfaces and observed no hindrance of cell growth caused by the peptide nanostructures; furthermore we studied the properties of PNWs by investigating their influence on the electrochemical behavior of gold electrodes. The PNWs were functionalized with polypyrrole (PPy) by chemical polymerization, therefore creating conducting peptide/polymer nanowire structures vertically attached to a metal electrode. The electroactivity of such structures was characterized by cyclic voltammetry. The PNW/PPy modified electrodes were finally used as amperometric dopamine sensors, yielding a detection limit of 3,1 microM.

In this work we introduce a novel out-of-plane electrode with pronounced scalloped surface and high aspect ratio for electrical recordings of brain tissue in vitro, with the aim to reduce significantly the impedance of the measuring system. The profile and height of the structures is tailored by means of silicon fabrication techniques that sharpen them progressively and in a controlled manner. We will show that the use of the scalloped area achieves a great decrease in impedance, which is very significant for a reduction of noise in electrical measurements. The measured impedance reflects an important improvement in comparison with already available systems. Additionally, first test of durability prove the robustness of these needle-like electrodes during indentation motions. In conclusion, the resulting electrodes are robust, sharp structures that decrease the typical impedance of microelectrodes and are potentially suited for indentation and recording of brain tissue.

In this report electrostatic force microscopy (EFM) is used to study different peptide self-assembled structures such as tubes and particles. It is shown that not only geometrical information can be obtained using EFM, but also information about the composition of different structures. In particular we use EFM to investigate the structures of diphenylalanine peptide tubes, particles, and CSGAITIG peptide particles placed on pre-fabricated SiO2 surfaces with a backgate. We show that the cavity in the peptide tubes could be due to the presence of water residues. Additionally we show that self-assembled amyloid peptides form spherical solid structures containing the same self-assembled peptide in its interior. In both cases transmission electron microscopy is used to verify these structures. Further, the limitations of the EFM technique are discussed, especially when the observed structures become small compared with the radius of the AFM tip used. Finally, an agreement between the detected signal and the structure of the hollow peptide tubes is demonstrated. SCANNING 33: 201–207, 2011. © 2011 Wiley Periodicals, Inc.

Magneto-resistive sensors capable of detecting superparamagnetic micro-/nano-sized beads are promising alternatives to standard diagnostic assays based on absorbance or fluorescence and streptavidin-functionalized beads are widely used as an integral part of these sensors. Here we have developed an immunomicroarray for systematic studies of the binding properties of 10 different micro-/nano-sized streptavidin-functionalized beads to a biotin substrate immobilized on SiO(2) with or without surface modification. SiO(2) surface cleaning, immobilized substrate concentration and surface blocking conditions were optimized. Polyethylene glycol-based surfaces with different end groups on the anchor molecule, 2,4,6-trichloro-1,3,5-triazine (TsT), were synthesized and compared with the standard (3-aminopropyl)triethoxysilane (APTS)/glutaraldehyde chemistry. APTS/glutaraldehyde, directly linked TsT and bare H(2)O(2)-activated SiO(2) performed better than polyethylene glycol-modified surfaces. Two beads, Masterbeads and M-280 beads, were found to give superior results compared with other bead types. Antibody/antigen interactions, illustrated by C-reactive protein, were best performed with Masterbeads. The results provide important information concerning the surface binding properties of streptavidin-functionalized beads and the immunomicroarray can be used when optimizing the performance of bead-based biosensors.

Self-assembled amyloid peptide nanotubes (SAPNT) were manipulated and immobilized using dielectrophoresis. Micro-patterned electrodes of Au were fabricated by photolithography and lifted off on a silicon dioxide layer. SAPNT were manipulated by adjusting the amplitude and frequency of the applied voltage. The immobilized SAPNT were evaluated by SEM and atomic force microscopy. The conductivity of the immobilized SAPNT was studied by I-V characterization, for both single SAPNT and bundles. This work illustrates a way to manipulate and integrate biological nanostructures into novel bio-nanoassemblies with concrete applications, such as field-effect transistors, microprobes, microarrays, and biosensing devices.