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Field-effect-based electrolyte-insulator-semiconductor (EIS) sensors were modified with a bilayer of positively charged weak polyelectrolyte (poly(allylamine hydrochloride) (PAH)) and probe single-stranded DNA (ssDNA) and are used for the detection of complementary single-stranded target DNA (cDNA) in different test solutions. The sensing mechanism is based on the detection of the intrinsic molecular charge of target cDNA molecules after the hybridization event between cDNA and immobilized probe ssDNA. The test solutions contain synthetic cDNA oligonucleotides (with a sequence of tuberculosis mycobacteria genome) or PCR-amplified DNA (which origins from a template DNA strand that has been extracted from Mycobacterium avium paratuberculosis-spiked human sputum samples), respectively. Sensor responses up to 41 mV have been measured for the test solutions with DNA, while only small signals of ∼5 mV were detected for solutions without DNA. The lower detection limit of the EIS sensors was ∼0.3 nM, and the sensitivity was ∼7.2 mV/decade. Fluorescence experiments using SybrGreen I fluorescence dye support the electrochemical results.
Detection of triacetone triperoxide using temperature cycled metal-oxide semiconductor gas sensors
(2015)
On-line monitoring of the metabolic activity of microorganisms involved in intermediate stages of biogas production plays an important role to avoid undesirable “down times” during the biogas production. In order to control this process, an on-chip differential measuring system based on the light-addressable potentiometric sensor (LAPS) principle combined with a 3D-printed multi-chamber structure has been realized. As a test microorganism, Escherichia coli K12 (E. coli K12) were used for cell-based measurements. Multi-chamber structures were developed to determine the metabolic activity of E. coli K12 in suspension for a different number of cells, responding to the addition of a constant or variable amount of glucose concentrations, enabling differential and simultaneous measurements.
Determination of the frictional coefficient of the implant-antler interface : experimental approach
(2012)
The similar bone structure of reindeer antler to human bone permits studying the osseointegration of dental implants in the jawbone. As the friction is one of the major factors that have a significant influence on the initial stability of immediately loaded dental implants, it is essential to define the frictional coefficient of the implant-antler interface. In this study, the kinetic frictional forces at the implant-antler interface were measured experimentally using an optomechanical setup and a stepping motor controller under different axial loads and sliding velocities. The corresponding mean values of the static and kinetic frictional coefficients were within the range of 0.5–0.7 and 0.3–0.5, respectively. An increase in the frictional forces with increasing applied axial loads was registered. The measurements showed an evidence of a decrease in the magnitude of the frictional coefficient with increasing sliding velocity. The results of this study provide a considerable assessment to clarify the suitable frictional coefficient to be used in the finite element contact analysis of antler specimens.
The capacitive electrolyte–insulator–semiconductor (EIS) structure is a typical device based on a field-effect sensor platform. With a simple silicon-based structure, EIS have been useful for several sensing applications, especially with incorporation of nanostructured films to modulate the ionic transport and the flat-band potential. In this paper, we report on ion transport and changes in flat-band potential in EIS sensors made with layer-by-layer films containing poly(amidoamine) (PAMAM) dendrimer and single-walled carbon nanotubes (SWNTs) adsorbed on p-Si/SiO 2 /Ta 2 O 5 chips with an Al ohmic contact. The impedance spectra were fitted using an equivalent circuit model, from which we could determine parameters such as the double-layer capacitance. This capacitance decreased with the number of bilayers owing to space charge accumulated at the electrolyte–insulator interface, up to three PAMAM/SWNTs bilayers, after which it stabilized. The charge-transfer resistance was also minimum for three bilayers, thus indicating that this is the ideal architecture for an optimized EIS performance. The understanding of the influence of nanostructures and the fine control of operation parameters pave the way for optimizing the design and performance of new EIS sensors.
Booster stations can fulfill a varying pressure demand with high energy-efficiency, because individual pumps can be deactivated at smaller loads. Although this is a seemingly simple approach, it is not easy to decide precisely when to activate or deactivate pumps. Contemporary activation controls derive the switching points from the current volume flow through the system. However, it is not measured directly for various reasons. Instead, the controller estimates the flow based on other system properties. This causes further uncertainty for the switching decision. In this paper, we present a method to find a robust, yet energy-efficient activation strategy.
In this work, we present a compact, bifunctional chip-based sensor setup that measures the temperature and electrical conductivity of water samples, including specimens from rivers and channels, aquaculture, and the Atlantic Ocean. For conductivity measurements, we utilize the impedance amplitude recorded via interdigitated electrode structures at a single triggering frequency. The results are well in line with data obtained using a calibrated reference instrument. The new setup holds for conductivity values spanning almost two orders of magnitude (river versus ocean water) without the need for equivalent circuit modelling. Temperature measurements were performed in four-point geometry with an on-chip platinum RTD (resistance temperature detector) in the temperature range between 2 °C and 40 °C, showing no hysteresis effects between warming and cooling cycles. Although the meander was not shielded against the liquid, the temperature calibration provided equivalent results to low conductive Milli-Q and highly conductive ocean water. The sensor is therefore suitable for inline and online monitoring purposes in recirculating aquaculture systems.
Chemical imaging systems allow the visualisation of the distribution of chemical species on the sensor surface. This work represents a new flexible approach to read out light-addressable potentiometric sensors (LAPS) with the help of a digital light processing (DLP) set-up. The DLP, known well for video projectors, consists of a mirror-array MEMS device, which allows fast and flexible generation of light patterns. With the help of these light patterns, the sensor surface of the LAPS device can be addressed. The DLP approach has several advantages compared to conventional LAPS set-ups, e.g., the spot size and the shape of the light pointer can be changed easily and no mechanical movement is necessary, which reduces the size of the set-up and increases the stability and speed of the measurement. In addition, the modulation frequency and intensity of the light beam are important parameters of the LAPS set-up. Within this work, the authors will discuss two different ways of light modulation by the DLP set-up, investigate the influence of different modulation frequencies and different light intensities as well as demonstrate the scanning capabilities of the new set-up by pH mapping on the sensor surface.
A capacitive electrolyte-insulator-semiconductor (EIS) field-effect biosensor for acetoin detection has been presented for the first time. The EIS sensor consists of a layer structure of Al/p-Si/SiO₂/Ta₂O₅/enzyme acetoin reductase. The enzyme, also referred to as butane-2,3-diol dehydrogenase from B. clausii DSM 8716T, has been recently characterized. The enzyme catalyzes the (R)-specific reduction of racemic acetoin to (R,R)- and meso-butane-2,3-diol, respectively. Two different enzyme immobilization strategies (cross-linking by using glutaraldehyde and adsorption) have been studied. Typical biosensor parameters such as optimal pH working range, sensitivity, hysteresis, linear concentration range and long-term stability have been examined by means of constant-capacitance (ConCap) mode measurements. Furthermore, preliminary experiments have been successfully carried out for the detection of acetoin in diluted white wine samples.
An enzyme-based multi-parameter biosensor is developed for monitoring the concentration of formate, d-lactate, and l-lactate in biological samples. The sensor is based on the specific dehydrogenation by an oxidized β-nicotinamide adenine dinucleotide (NAD+)-dependent dehydrogenase (formate dehydrogenase, d-lactic dehydrogenase, and l-lactic dehydrogenase, respectively) in combination with a diaphorase from Clostridium kluyveri (EC 1.8.1.4). The enzymes are immobilized on a platinum working electrode by cross-linking with glutaraldehyde (GA). The principle of the determination scheme in case of l-lactate is as follows: l-lactic dehydrogenase (l-LDH) converts l-lactate into pyruvate by reaction with NAD+. In the presence of hexacyanoferrate(III), the resulting reduced β-nicotinamide adenine dinucleotide (NADH) is then regenerated enzymatically by diaphorase. The electrochemical detection is based on the current generated by oxidation of hexacyanoferrate(II) at an applied potential of +0.3 V vs. an Ag/AgCl reference electrode. The biosensor will be electrochemically characterized in terms of linear working range and sensitivity. Additionally, the successful practical application of the sensor is demonstrated in an extract from maize silage.
Within the present work a sterilization process by a heated gas mixture that contains hydrogen peroxide (H₂O₂) is validated by experiments and numerical modeling techniques. The operational parameters that affect the sterilization efficacy are described alongside the two modes of sterilization: gaseous and condensed H₂O₂. Measurements with a previously developed H₂O₂ gas sensor are carried out to validate the applied H₂O₂ gas concentration during sterilization. We performed microbiological tests at different H₂O₂ gas concentrations by applying an end-point method to carrier strips, which contain different inoculation loads of Geobacillus stearothermophilus spores. The analysis of the sterilization process of a pharmaceutical glass vial is performed by numerical modeling. The numerical model combines heat- and advection-diffusion mass transfer with vapor–pressure equations to predict the location of condensate formation and the concentration of H₂O₂ at the packaging surfaces by changing the gas temperature. For a sterilization process of 0.7 s, a H₂O₂ gas concentration above 4% v/v is required to reach a log-count reduction above six. The numerical results showed the location of H₂O₂ condensate formation, which decreases with increasing sterilant-gas temperature. The model can be transferred to different gas nozzle- and packaging geometries to assure the absence of H₂O₂ residues.
Glucose oxidase (GOx) is an enzyme frequently used in glucose biosensors. As increased temperatures can enhance the performance of electrochemical sensors, we investigated the impact of temperature pulses on GOx that was drop-coated on flattened Pt microwires. The wires were heated by an alternating current. The sensitivity towards glucose and the temperature stability of GOx was investigated by amperometry. An up to 22-fold increase of sensitivity was observed. Spatially resolved enzyme activity changes were investigated via scanning electrochemical microscopy. The application of short (<100 ms) heat pulses was associated with less thermal inactivation of the immobilized GOx than long-term heating.
In industrial processes there is a variety of heavy metals (e.g., copper, zinc, cadmium, and lead) in use for wires, coatings, paints, alloys, batteries, etc. Since the application of these transition metals for industry is inevitable, it is a vital task to develop proper analytical techniques for their monitoring at low activity levels, especially because most of these elements are acutely toxic for biological organisms. The determination of ions in solution by means of a simple and inexpensive sensor array is, therefore, a promising task. In this work, a sensor array with heavy metal-sensitive chalcogenide glass membranes for the simultaneous detection of the four ions Ag⁺, Cu2⁺, Cd2⁺, and Pb2⁺ in solution is realized. The results of the physical characterization by means of microscopy, profilometry, Rutherford backscattering spectroscopy (RBS), and scanning electron microscopy (SEM) as well as the electrochemical characterization by means of potentiometric measurements are presented. Additionally, the possibility to expand the sensor array by polymeric sensor membranes is discussed.
The discovery of human induced pluripotent stem cells reprogrammed from somatic cells [1] and their ability to differentiate into cardiomyocytes (hiPSC-CMs) has provided a robust platform for drug screening [2]. Drug screenings are essential in the development of new components, particularly for evaluating the potential of drugs to induce life-threatening pro-arrhythmias. Between 1988 and 2009, 14 drugs have been removed from the market for this reason [3]. The microelectrode array (MEA) technique is a robust tool for drug screening as it detects the field potentials (FPs) for the entire cell culture. Furthermore, the propagation of the field potential can be examined on an electrode basis. To analyze MEA measurements in detail, we have developed an open-source tool.
Three amperometric biosensors have been developed for the detection of L-malic acid, fumaric acid, and L -aspartic acid, all based on the combination of a malate-specific dehydrogenase (MDH, EC 1.1.1.37) and diaphorase (DIA, EC 1.8.1.4). The stepwise expansion of the malate platform with the enzymes fumarate hydratase (FH, EC 4.2.1.2) and aspartate ammonia-lyase (ASPA, EC 4.3.1.1) resulted in multi-enzyme reaction cascades and, thus, augmentation of the substrate spectrum of the sensors. Electrochemical measurements were carried out in presence of the cofactor β-nicotinamide adenine dinucleotide (NAD+) and the redox mediator hexacyanoferrate (III) (HCFIII). The amperometric detection is mediated by oxidation of hexacyanoferrate (II) (HCFII) at an applied potential of + 0.3 V vs. Ag/AgCl. For each biosensor, optimum working conditions were defined by adjustment of cofactor concentrations, buffer pH, and immobilization procedure. Under these improved conditions, amperometric responses were linear up to 3.0 mM for L-malate and fumarate, respectively, with a corresponding sensitivity of 0.7 μA mM−1 (L-malate biosensor) and 0.4 μA mM−1 (fumarate biosensor). The L-aspartate detection system displayed a linear range of 1.0–10.0 mM with a sensitivity of 0.09 μA mM−1. The sensor characteristics suggest that the developed platform provides a promising method for the detection and differentiation of the three substrates.
Hydrogen peroxide (H2O2) is a typical surface sterilization agent for packaging materials used in the pharmaceutical, food and beverage industries. We use the finite-elements method to analyze the conceptual design of an in-line thermal evaporation unit to produce a heated gas mixture of air and evaporated H2O2 solution. For the numerical model, the required phase-transition variables of pure H2O2 solution and of the aerosol mixture are acquired from vapor-liquid equilibrium (VLE) diagrams derived from vapor-pressure formulations. This work combines homogeneous single-phase turbulent flow with heat-transfer physics to describe the operation of the evaporation unit. We introduce the apparent heat-capacity concept to approximate the non-isothermal phase-transition process of the H2O2-containing aerosol. Empirical and analytical functions are defined to represent the temperature- and pressure-dependent material properties of the aqueous H2O2 solution, the aerosol and the gas mixture. To validate the numerical model, the simulation results are compared to experimental data on the heating power required to produce the gas mixture. This shows good agreement with the deviations below 10%. Experimental observations on the formation of deposits due to the evaporation of stabilized H2O2 solution fits the prediction made from simulation results.
Development of an optimized LSO/LuYAP phoswich detector head for the Lausanne ClearPET demonstrator
(2006)
This paper describes the LSO/LuYAP phoswich detector head developed for the ClearPET small animal PET scanner demonstrator that is under construction in Lausanne within the Crystal Clear Collaboration. The detector head consists of a dual layer of 8×8 LSO and LuYAP crystal arrays coupled to a multi-anode photomultiplier tube (Hamamatsu R7600-M64). Equalistion of the LSO/LuYAP light collection is obtained through partial attenuation of the LSO scintillation light using a thin aluminum deposit of 20-35 nm on LSO and appropriate temperature regulation of the phoswich head between 30°C to 60°C. At 511keV, typical FWHM energy resolutions of the pixels of a phoswich head amounts to (28±2)% for LSO and (25±2)% for LuYAP. The LSO versus LuYAP crystal identification efficiency is better than 98%. Six detector modules have been mounted on a rotating gantry. Axial and tangential spatial resolutions were measured up to 4 cm from the scanner axis and compared to Monte Carlo simulations using GATE. FWHM spatial resolution ranges from 1.3 mm on axis to 2.6 mm at 4 cm from the axis.
As a semiconductor-based electrochemical sensor, the light-addressable potentiometric sensor (LAPS) can realize two dimensional visualization of (bio-)chemical reactions at the sensor surface addressed by localized illumination. Thanks to this imaging capability, various applications in biochemical and biomedical fields are expected, for which the spatial resolution is critically significant. In this study, therefore, the spatial resolution of the LAPS was investigated in detail based on the device simulation. By calculating the spatiotemporal change of the distributions of electrons and holes inside the semiconductor layer in response to a modulated illumination, the photocurrent response as well as the spatial resolution was obtained as a function of various parameters such as the thickness of the Si substrate, the doping concentration, the wavelength and the intensity of illumination.
The simulation results verified that both thinning the semiconductor substrate and increasing the doping concentration could improve the spatial resolution, which were in good agreement with known experimental results and theoretical analysis. More importantly, new findings of interests were also obtained. As for the dependence on the wavelength of illumination, it was found that the known dependence was not always the case. When the Si substrate was thick, a longer wavelength resulted in a higher spatial resolution which was known by experiments. When the Si substrate was thin, however, a longer wavelength of light resulted in a lower spatial resolution. This finding was explained as an effect of raised concentration of carriers, which reduced the thickness of the space charge region.
The device simulation was found to be helpful to understand the relationship between the spatial resolution and device parameters, to understand the physics behind it, and to optimize the device structure and measurement conditions for realizing higher performance of chemical imaging systems.
A novel photoexcitation method for the light-addressable potentiometric sensor (LAPS) realized a higher spatial resolution of chemical imaging. In this method, a modulated light probe, which generates the alternating photocurrent signal, is surrounded by a ring of constant light, which suppresses the lateral diffusion of photocarriers by enhancing recombination. A device simulation verified that a higher spatial resolution could be obtained by adjusting the gap between the modulated and constant light. It was also found that a higher intensity and a longer wavelength of constant light was more effective. However, there exists a tradeoff between the spatial resolution and the amplitude of the photocurrent, and thus, the signal-to-noise ratio. A tilted incidence of constant light was applied, which could achieve even higher resolution with a smaller loss of photocurrent.
Extracellular acidification is a basic indicator for alterations in two vital metabolic pathways: glycolysis and cellular respiration. Measuring these alterations by monitoring extracellular acidification using cell-based biosensors such as LAPS plays an important role in studying these pathways whose disorders are associated with numerous diseases including cancer. However, the surface of the biosensors must be specially tailored to ensure high cell compatibility so that cells can represent more in vivo-like behavior, which is critical to gain more realistic in vitro results from the analyses, e.g., drug discovery experiments. In this work, O2 plasma patterning on the LAPS surface is studied to enhance surface features of the sensor chip, e.g., wettability and biofunctionality. The surface treated with O2 plasma for 30 s exhibits enhanced cytocompatibility for adherent CHO–K1 cells, which promotes cell spreading and proliferation. The plasma-modified LAPS chip is then integrated into a microfluidic system, which provides two identical channels to facilitate differential measurements of the extracellular acidification of CHO–K1 cells. To the best of our knowledge, it is the first time that extracellular acidification within microfluidic channels is quantitatively visualized as differential (bio-)chemical images.
A light-addressable potentiometric sensor (LAPS) is a field-effect-based potentiometric sensor with an electrolyte/insulator/semiconductor (EIS) structure, which is able to monitor analyte concentrations of (bio-)chemical species in aqueous solutions in a spatially resolved way. Therefore, it is also an appropriate tool to record 2D-chemical images of concentration variations on the sensor surface. In the present work, two differential, LAPS-based measurement principles are introduced to determine the metabolic activity of Escherichia coli (E. coli) K12 and Chinese hamster ovary (CHO) cells as test microorganisms. Hereby, we focus on i) the determination of the extracellular acidification rate (ΔpH/min) after adding glucose solutions to the cell suspensions; and ii) recording the amplitude increase of the photocurrent (Iph) related to the produced acids from E. coli K12 bacteria and CHO cells on the sensor surface by 2D-chemical imaging. For this purpose, 3D-printed multi-chamber structures were developed and mounted on the planar sensor-chip surface to define four independent compartments, enabling differential measurements with varying cell concentrations. The differential concept allows eliminating unwanted drift effects and, with the four-chamber structures, measurements on the different cell concentrations were performed simultaneously, thus reducing also the overall measuring time.
Differential modulation of valence and arousal in high-alexithymic and low-alexithymic individuals
(2010)
High-alexithymic individuals are characterized by an impaired ability to identify and communicate emotions whereas low-alexithymic individuals have a wide-ranging ability to deal with emotions. This study examined the hypothesis that valence and arousal modifications of emotional stimuli differentially modulate cortical regions in high-alexithymic and low-alexithymic individuals. To this end, 28 high-alexithymic and 25 low-alexithymic individuals were investigated with event-related fMRI using visual emotional stimuli. We found differential neural activations in the dorsal anterior cingulate, the insula and the amygdala. We suggest that these differences may account for the impaired ability of high-alexithymic individuals to appropriately handle emotional stimuli.
We propose a stochastic programming method to analyse limit and shakedown of structures under random strength with lognormal distribution. In this investigation a dual chance constrained programming algorithm is developed to calculate simultaneously both the upper and lower bounds of the plastic collapse limit or the shakedown limit. The edge-based smoothed finite element method (ES-FEM) using three-node linear triangular elements is used.
We propose the so-called chance constrained programming model of stochastic programming theory to analyze limit and shakedown loads of structures under random strength with a lognormal distribution. A dual chance constrained programming algorithm is developed to calculate simultaneously both the upper and lower bounds of the plastic collapse limit and the shakedown limit. The edge-based smoothed finite element method (ES-FEM) is used with three-node linear triangular elements.
Direct sampling method via Landweber iteration for an absorbing scatterer with a conductive boundary
(2024)
In this paper, we consider the inverse shape problem of recovering isotropic scatterers with a conductive boundary condition. Here, we assume that the measured far-field data is known at a fixed wave number. Motivated by recent work, we study a new direct sampling indicator based on the Landweber iteration and the factorization method. Therefore, we prove the connection between these reconstruction methods. The method studied here falls under the category of qualitative reconstruction methods where an imaging function is used to recover the absorbing scatterer. We prove stability of our new imaging function as well as derive a discrepancy principle for recovering the regularization parameter. The theoretical results are verified with numerical examples to show how the reconstruction performs by the new Landweber direct sampling method.
The deformation and damage laws of non-homogeneous irregular structural planes in rocks are the basis for studying the stability of rock engineering. To investigate the damage characteristics of rock containing non-parallel fissures, uniaxial compression tests and numerical simulations were conducted on sandstone specimens containing three non-parallel fissures inclined at 0°, 45° and 90° in this study. The characteristics of crack initiation and crack evolution of fissures with different inclinations were analyzed. A constitutive model for the discontinuous fractures of fissured sandstone was proposed. The results show that the fracture behaviors of fissured sandstone specimens are discontinuous. The stress–strain curves are non-smooth and can be divided into nonlinear crack closure stage, linear elastic stage, plastic stage and brittle failure stage, of which the plastic stage contains discontinuous stress drops. During the uniaxial compression test, the middle or ends of 0° fissures were the first to crack compared to 45° and 90° fissures. The end with small distance between 0° and 45° fissures cracked first, and the end with large distance cracked later. After the final failure, 0° fissures in all specimens were fractured, while 45° and 90° fissures were not necessarily fractured. Numerical simulation results show that the concentration of compressive stress at the tips of 0°, 45° and 90° fissures, as well as the concentration of tensile stress on both sides, decreased with the increase of the inclination angle. A constitutive model for the discontinuous fractures of fissured sandstone specimens was derived by combining the logistic model and damage mechanic theory. This model can well describe the discontinuous drops of stress and agrees well with the whole processes of the stress–strain curves of the fissured sandstone specimens.