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Penicillin detection by means of field-effect based sensors: EnFET, capacitive EIS sensor or LAPS?
(2000)
The LAPS (light-addressable potentiometric sensor) platform is one of the most attractive approaches for chemical and biological sensing with many applications ranging from pH and ion/analyte concentration measurements up to cell metabolism detection and chemical imaging. However, although it is generally accepted that LAPS measurements are spatially resolved, the light-addressability feature of LAPS devices has not been discussed in detail so far. In this work, an extended electrical equivalent-circuit model of the LAPS has been presented, which takes into account possible cross-talk effects due to the capacitive coupling of the non-illuminated region. A shunting effect of the non-illuminated area on the measured photocurrent and addressability of LAPS devices has been studied. It has been shown, that the measured photocurrent will be determined not only by the local interfacial potential in the illuminated region but also by possible interfacial potential changes in the non-illuminated region, yielding cross-talk effects. These findings were supported by the experimental investigations of a penicillin-sensitive multi-spot LAPS and a metal-insulator-semiconductor LAPS as model systems.
The on-chip integration of multiple biochemical sensors based on field-effect electrolyte-insulator-semiconductor capacitors (EISCAP) is challenging due to technological difficulties in realization of electrically isolated EISCAPs on the same Si chip. In this work, we present a new simple design for an array of on-chip integrated, individually electrically addressable EISCAPs with an additional control gate (CG-EISCAP). The existence of the CG enables an addressable activation or deactivation of on-chip integrated individual CG-EISCAPs by simple electrical switching the CG of each sensor in various setups, and makes the new design capable for multianalyte detection without cross-talk effects between the sensors in the array. The new designed CG-EISCAP chip was modelled in so-called floating/short-circuited and floating/capacitively-coupled setups, and the corresponding electrical equivalent circuits were developed. In addition, the capacitance-voltage curves of the CG-EISCAP chip in different setups were simulated and compared with that of a single EISCAP sensor. Moreover, the sensitivity of the CG-EISCAP chip to surface potential changes induced by biochemical reactions was simulated and an impact of different parameters, such as gate voltage, insulator thickness and doping concentration in Si, on the sensitivity has been discussed.
An array of electrically isolated nanoplate field-effect silicon-on-insulator (SOI) capacitors as a new transducer structure for multiparameter (bio-)chemical sensing is presented. The proposed approach allows addressable biasing and electrical readout of multiple nanoplate field-effect capacitive (bio-)chemical sensors on the same SOI chip, as well as differential-mode measurements. The realized sensor chip has been applied for pH and penicillin concentration measurements, electrical monitoring of polyelectrolyte multilayer formation, and the label-free electrical detection of consecutive deoxyribonucleic acid (DNA) hybridization and denaturation events.
Field-effect capacitive electrolyte-insulator-semiconductor (EIS) sensors functionalised with citrate-capped gold nanoparticles (AuNP) have been used for the electrostatic detection of macromolecules by their intrinsic molecular charge. The EIS sensor detects the charge changes in the AuNP/macromolecule hybrids induced by the adsorption or binding events. A feasibility of the proposed detection scheme has been exemplary demonstrated by realising EIS sensors for the detection of poly-D-lysine molecules.
The semiconductor field-effect platform represents a powerful tool for detecting the adsorption and binding of charged macromolecules with direct electrical readout. In this work, a capacitive electrolyte–insulator–semiconductor (EIS) field-effect sensor consisting of an Al-p-Si-SiO2 structure has been applied for real-time in situ electrical monitoring of the layer-by-layer formation of polyelectrolyte (PE) multilayers (PEM). The PEMs were deposited directly onto the SiO2 surface without any precursor layer or drying procedures. Anionic poly(sodium 4-styrene sulfonate) and cationic weak polyelectrolyte poly(allylamine hydrochloride) have been chosen as a model system. The effect of the ionic strength of the solution, polyelectrolyte concentration, number and polarity of the PE layers on the characteristics of the PEM-modified EIS sensors have been studied by means of capacitance–voltage and constant-capacitance methods. In addition, the thickness, surface morphology, roughness and wettabilityof the PE mono- and multilayers have been characterised by ellipsometry, atomic force microscopy and water contact-angle methods, respectively. To explain potential oscillations on the gate surface and signal behaviour of the capacitive field-effect EIS sensor modified with a PEM, a simplified electrostatic model that takes into account the reduced electrostatic screening of PE charges by mobile ions within the PEM has been proposed and discussed.
An ISFET-based penicillin sensor with high sensitivity, low detection limit and long lifetime
(2001)
The coupling of charged molecules, nanoparticles, and more generally, inorganic/organic nanohybrids with semiconductor field-effect devices based on an electrolyte–insulator–semiconductor (EIS) system represents a very promising strategy for the active tuning of electrochemical properties of these devices and, thus, opening new opportunities for label-free biosensing by the intrinsic charge of molecules. The simplest field-effect sensor is a capacitive EIS sensor, which represents a (bio-)chemically sensitive capacitor. In this chapter, selected examples of recent developments in the field of label-free biosensing using nanomaterial-modified capacitive EIS sensors are summarized. In the first part, we present applications of EIS sensors modified with negatively charged gold nanoparticles for the label-free electrostatic detection of positively charged small proteins and macromolecules, for monitoring the layer-by-layer formation of oppositely charged polyelectrolyte (PE) multilayers as well as for the development of an enzyme-based biomolecular logic gate. In the second part, examples of a label-free detection by means of EIS sensors modified with a positively charged weak PE layer are demonstrated. These include electrical detection of on-chip and in-solution hybridized DNA (deoxyribonucleic acid) as well as an EIS sensor with pH-responsive weak PE/enzyme multilayers for enhanced field-effect biosensing.
Among the variety of transducer concepts proposed for label-free detection of biomolecules, the semiconductor field-effect device (FED) is one of the most attractive platforms. As medical techniques continue to progress towards diagnostic and therapies based on biomarkers, the ability of FEDs for a label-free, fast and real-time detection of multiple pathogenic and physiologically relevant molecules with high specificity and sensitivity offers very promising prospects for their application in point-of-care and personalized medicine for an early diagnosis and treatment of diseases. The presented paper reviews recent advances and current trends in research and development of different FEDs for label-free, direct electrical detection of charged biomolecules by their intrinsic molecular charge. The authors are mainly focusing on the detection of the DNA hybridization event, antibody-antigen affinity reaction as well as clinically relevant biomolecules such as cardiac and cancer biomarkers.
Electrolyte-insulator-semiconductor (EIS) field-effect sensors belong to a new generation of electronic chips for biochemical sensing, enabling a direct electronic readout. The review gives an overview on recent advances and current trends in the research and development of chemical sensors and biosensors based on the capacitive field-effect EIS structure—the simplest field-effect device, which represents a biochemically sensitive capacitor. Fundamental concepts, physicochemical phenomena underlying the transduction mechanism and application of capacitive EIS sensors for the detection of pH, ion concentrations, and enzymatic reactions, as well as the label-free detection of charged molecules (nucleic acids, proteins, and polyelectrolytes) and nanoparticles, are presented and discussed.
Biologically sensitive field-effect devices (BioFEDs) advantageously combine the electronic field-effect functionality with the (bio)chemical receptor’s recognition ability for (bio)chemical sensing. In this review, basic and widely applied device concepts of silicon-based BioFEDs (ion-sensitive field-effect transistor, silicon nanowire transistor, electrolyte-insulator-semiconductor capacitor, light-addressable potentiometric sensor) are presented and recent progress (from 2019 to early 2021) is discussed. One of the main advantages of BioFEDs is the label-free sensing principle enabling to detect a large variety of biomolecules and bioparticles by their intrinsic charge. The review encompasses applications of BioFEDs for the label-free electrical detection of clinically relevant protein biomarkers, deoxyribonucleic acid molecules and viruses, enzyme-substrate reactions as well as recording of the cell acidification rate (as an indicator of cellular metabolism) and the extracellular potential.
Functional testing and characterisation of ISFETs on wafer level by means of a micro-droplet cell
(2006)
A wafer-level functionality testing and characterisation system for ISFETs (ionsensitive field-effect transistor) is realised by means of integration of a specifically designed capillary electrochemical micro-droplet cell into a commercial wafer prober-station. The developed system allows the identification and selection of “good” ISFETs at the earliest stage and to avoid expensive bonding, encapsulation and packaging processes for nonfunctioning ISFETs and thus, to decrease costs, which are wasted for bad dies. The developed system is also feasible for wafer-level characterisation of ISFETs in terms of sensitivity, hysteresis and response time. Additionally, the system might be also utilised for wafer-level testing of further electrochemical sensors.
Application of a (bio-)chemical sensor (ISFET) for the detection of physical parameters in liquids
(2003)
Capacitive field-effect sensors modified with a multi-enzyme membrane have been applied for an electronic transduction of biochemical signals processed by enzyme-based AND-Reset and OR-Reset logic gates. The local pH change at the sensor surface induced by the enzymatic reaction was used for the activation of the Reset function for the first time.
Nanoparticles are recognized as highly attractive tunable materials for designing field-effect biosensors with enhanced performance. In this work, we present a theoretical model for electrolyte-insulator-semiconductor capacitors (EISCAP) decorated with ligand-stabilized charged gold nanoparticles. The charged AuNPs are taken into account as additional, nanometer-sized local gates. The capacitance-voltage (C–V) curves and constant-capacitance (ConCap) signals of the AuNP-decorated EISCAPs have been simulated. The impact of the AuNP coverage on the shift of the C–V curves and the ConCap signals was also studied experimentally on Al–p-Si–SiO₂ EISCAPs decorated with positively charged aminooctanethiol-capped AuNPs. In addition, the surface of the EISCAPs, modified with AuNPs, was characterized by scanning electron microscopy for different immobilization times of the nanoparticles.
Coronavirus disease 2019 (COVID-19) is a novel human infectious disease provoked by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Currently, no specific vaccines or drugs against COVID-19 are available. Therefore, early diagnosis and treatment are essential in order to slow the virus spread and to contain the disease outbreak. Hence, new diagnostic tests and devices for virus detection in clinical samples that are faster, more accurate and reliable, easier and cost-efficient than existing ones are needed. Due to the small sizes, fast response time, label-free operation without the need for expensive and time-consuming labeling steps, the possibility of real-time and multiplexed measurements, robustness and portability (point-of-care and on-site testing), biosensors based on semiconductor field-effect devices (FEDs) are one of the most attractive platforms for an electrical detection of charged biomolecules and bioparticles by their intrinsic charge. In this review, recent advances and key developments in the field of label-free detection of viruses (including plant viruses) with various types of FEDs are presented. In recent years, however, certain plant viruses have also attracted additional interest for biosensor layouts: Their repetitive protein subunits arranged at nanometric spacing can be employed for coupling functional molecules. If used as adapters on sensor chip surfaces, they allow an efficient immobilization of analyte-specific recognition and detector elements such as antibodies and enzymes at highest surface densities. The display on plant viral bionanoparticles may also lead to long-time stabilization of sensor molecules upon repeated uses and has the potential to increase sensor performance substantially, compared to conventional layouts. This has been demonstrated in different proof-of-concept biosensor devices. Therefore, richly available plant viral particles, non-pathogenic for animals or humans, might gain novel importance if applied in receptor layers of FEDs. These perspectives are explained and discussed with regard to future detection strategies for COVID-19 and related viral diseases.
A field-effect biosensor employing tobacco mosaic virus (TMV) particles as scaffolds for enzyme immobilization is presented. Nanotubular TMV scaffolds allow a dense immobilization of precisely positioned enzymes with retained activity. To demonstrate feasibility of this new strategy, a penicillin sensor has been developed by coupling a penicillinase with virus particles as a model system. The developed field-effect penicillin biosensor consists of an Al-p-Si-SiO₂-Ta₂O₅-TMV structure and has been electrochemically characterized in buffer solutions containing different concentrations of penicillin G. In addition, the morphology of the biosensor surface with virus particles was characterized by scanning electron microscopy and atomic force microscopy methods. The sensors possessed a high penicillin sensitivity of ~ 92 mV/dec in a nearly-linear range from 0.1 mM to 10 mM, and a low detection limit of about 50 µM. The long-term stability of the penicillin biosensor was periodically tested over a time period of about one year without any significant loss of sensitivity. The biosensor has also been successfully applied for penicillin detection in bovine milk samples.
Label-free sensing of biomolecules by their intrinsic molecular charge using field-effect devices
(2015)
Label-free Electrostatic Detection of DNA Amplification by PCR Using Capacitive Field-effect Devices
(2016)
A capacitive field-effect EIS (electrolyte-insulator-semiconductor) sensor modified with a positively charged weak polyelectrolyte of poly(allylamine hydrochloride) (PAH)/single-stranded probe DNA (ssDNA) bilayer has been used for a label-free electrostatic detection of pathogen-specific DNA amplification via polymerase chain reaction (PCR). The sensor is able to distinguish between positive and negative PCR solutions, to detect the existence of target DNA amplicons in PCR samples and thus, can be used as tool for a quick verification of DNA amplification and the successful PCR process.
Novel concepts for flow-rate and flow-direction determination by means of pH-sensitive ISFETs
(2001)
Sensing charged macromolecules with nanocrystalline diamond-based field-effect capacitive sensors
(2008)
A new and simple method for nanostructuring using conventional photolithography and layer expansion or pattern-size reduction technique is presented, which can further be applied for the fabrication of different nanostructures and nano-devices. The method is based on the conversion of a photolithographically patterned metal layer to a metal-oxide mask with improved pattern-size resolution using thermal oxidation. With this technique, the pattern size can be scaled down to several nanometer dimensions. The proposed method is experimentally demonstrated by preparing nanostructures with different configurations and layouts, like circles, rectangles, trapezoids, “fluidic-channel”-, “cantilever”- and meander-type structures.
Optoelectronic Properties of Nanostructured Ensembles Controlled by Biomolecular Logic Systems
(2008)
Attitude and Orbital Dynamics Modeling for an Uncontrolled Solar-Sail Experiment in Low-Earth Orbit
(2015)
Gossamer-1 is the first project of the three-step Gossamer roadmap, the purpose of which is to develop, prove and demonstrate that solar-sail technology is a safe and reliable propulsion technique for long-lasting and high-energy missions. This paper firstly presents the structural analysis performed on the sail to understand its elastic behavior. The results are then used in attitude and orbital simulations. The model considers the main forces and torques that a satellite experiences in low-Earth orbit coupled with the sail deformation. Doing the simulations for varying initial conditions in attitude and rotation rate, the results show initial states to avoid and maximum rotation rates reached for correct and faulty deployment of the sail. Lastly comparisons with the classic flat sail model are carried out to test the hypothesis that the elastic behavior does play a role in the attitude and orbital behavior of the sail
The immobilization of NAD+-dependent dehydrogenases, in combination with a diaphorase, enables the facile development of multiparametric sensing devices. In this work, an amperometric biosensor array for simultaneous determination of ethanol, formate, d- and l-lactate is presented. Enzyme immobilization on platinum thin-film electrodes was realized by chemical cross-linking with glutaraldehyde. The optimization of the sensor performance was investigated with regard to enzyme loading, glutaraldehyde concentration, pH, cofactor concentration and temperature. Under optimal working conditions (potassium phosphate buffer with pH 7.5, 2.5 mmol L-1 NAD+, 2.0 mmol L-1 ferricyanide, 25 °C and 0.4% glutaraldehyde) the linear working range and sensitivity of the four sensor elements was improved. Simultaneous and cross-talk free measurements of four different metabolic parameters were performed successfully. The reliable analytical performance of the biosensor array was demonstrated by application in a clarified sample of inoculum sludge. Thereby, a promising approach for on-site monitoring of fermentation processes is provided.
Multi-analyte biosensors may offer the opportunity to perform cost-effective and rapid analysis with reduced sample volume, as compared to electrochemical biosensing of each analyte individually. This work describes the development of an enzyme-based biosensor system for multi-parametric determination of four different organic acids. The biosensor array comprises five working electrodes for simultaneous sensing of ethanol, formate, d-lactate, and l-lactate, and an integrated counter electrode. Storage stability of the biosensor was evaluated under different conditions (stored at +4 °C in buffer solution and dry at −21 °C, +4 °C, and room temperature) over a period of 140 days. After repeated and regular application, the individual sensing electrodes exhibited the best stability when stored at −21 °C. Furthermore, measurements in silage samples (maize and sugarcane silage) were conducted with the portable biosensor system. Comparison with a conventional photometric technique demonstrated successful employment for rapid monitoring of complex media.
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.
In this paper, methods of surface modification of different supports, i.e. glass and polymeric beads for enzyme immobilisation are described. The developed method of enzyme immobilisation is based on Schiff’s base formation between the amino groups on the enzyme surface and the aldehyde groups on the chemically modified surface of the supports. The surface of silicon modified by APTS and GOPS with immobilised enzyme was characterised by atomic force microscopy (AFM), time-of-flight secondary ion mass spectroscopy (ToF-SIMS) and infrared spectroscopy (FTIR). The supports with immobilised enzyme (urease) were also tested in combination with microreactors fabricated in silicon and Perspex, operating in a flow-through system. For microreactors filled with urease immobilised on glass beads (Sigma) and on polymeric beads (PAN), a very high and stable signal (pH change) was obtained. The developed method of urease immobilisation can be stated to be very effective.
In this paper, methods of sample preparation for potentiometric measurement of phenylalanine are presented. Basing on the spectrophotometric measurements of phenylalanine, the concentrations of reagents of the enzymatic reaction (10 mM L-Phe, 0,4 mM NAD+, 2U L-PheDH) were determined. Then, the absorption spectrum of the reaction product, NADH, was monitored (maximum peak at 340 nm). The results obtained by the spectrophotometric method were compared with the results obtained by the colourimetry, using pH indicators. The above-mentioned two methods will be used as references for potentiometric measurements of phenylalanine concentration.
Knowledge Management
(2001)
A Portable Implementation of Index Sequential Input-Output [Part 1] / Kurbel, Karl; Pietsch, W.
(1986)
A Portable Implementation of Index Sequential Input-Output [Part 2] / Kurbel, Karl; Pietsch, W.
(1986)
A Cooperative Work Environment for Evolutionary Software Development / Kurbel, K., Pietsch, W.
(1990)
IT Service Deployment
(2007)
IT Products are viewed and managed differently depending on the perspectives and the stage within the life cycle. A model is presented that integrates different perspectives and stages serving as an aid for the analysis of business models and focused positioning of IT-products. Four generic business models are analysed with regard to the product management function in general and the positioning field for IT-products specifically: off-the-shelf (license), license plus service, project, and system service (incl. cloud computing).
This paper investigates the interior transmission problem for homogeneous media via eigenvalue trajectories parameterized by the magnitude of the refractive index. In the case that the scatterer is the unit disk, we prove that there is a one-to-one correspondence between complex-valued interior transmission eigenvalue trajectories and Dirichlet eigenvalues of the Laplacian which turn out to be exactly the trajectorial limit points as the refractive index tends to infinity. For general simply-connected scatterers in two or three dimensions, a corresponding relation is still open, but further theoretical results and numerical studies indicate a similar connection.
Surgical clip applicator
(1996)
This paper describes two courses on
simulation methods for graduate students:
“Simulation Methods” and “Simulation and
Optimization in Virtual Engineering” The
courses were planned to teach young engineers
how to work with simulation software as well as
to understand the necessary mathematical background.
As simulation software COMSOL is
used. The main philosophy was to combine
theory and praxis in a way that motivates the
students. In addition “soft skills” should be
improved. This was achieved by project work as
final examination. As underlying didactical principle
the ideas of Bloom’s revised taxonomy
were followed. The paper basically focusses on
educational aspects, e.g. how to structure the
course, plan the exercises, organize the project
work and include practical COMSOL examples.
Often, detailed simulations of heat conduction in complicated, porous media have large runtimes. Then homogenization is a powerful tool to speed up the calculations by preserving accurate solutions at the same time. Unfortunately real structures are generally non-periodic, which requires unpractical, complicated homogenization techniques. We demonstrate in this paper, that the application of simple, periodic techniques to realistic media, that are just close to periodic, gives accurate, approximative solutions. In order to obtain effective parameters for the homogenized heat equation, we have to solve a so called “cell problem”. In contrast to periodic structures it is not trivial to determine a suitable unit cell, which represents a non-periodic media. To overcome this problem, we give a rule of thumb on how to choose a good cell. Finally we demonstrate the efficiency of our method for virtually generated foams as well as real foams and compare these results to periodic structures.
Numerical solution of the heat equation with non-linear, time derivative-dependent source term
(2010)
The mathematical modeling of heat conduction with adsorption effects in coated metal structures yields the heat equation with piecewise smooth coefficients and a new kind of source term. This term is special, because it is non-linear and furthermore depends on a time derivative. In our approach we reformulated this as a new problem for the usual heat equation, without source term but with a new non-linear coefficient. We gave an existence and uniqueness proof for the weak solution of the reformulated problem. To obtain a numerical solution, we developed a semi-implicit and a fully implicit finite volume method. We compared these two methods theoretically as well as numerically. Finally, as practical application, we simulated the heat conduction in coated aluminum fibers with adsorption in the zeolite coating. Copyright © 2010 John Wiley & Sons, Ltd.
Anyone who has always wanted to understand the hieroglyphs on Sheldon's blackboard in the TV series The Big Bang Theory or who wanted to know exactly what the fate of Schrödinger's cat is all about will find a short, descriptive introduction to the world of quantum mechanics in this essential. The text particularly focuses on the mathematical description in the Hilbert space. The content goes beyond popular scientific presentations, but is nevertheless suitable for readers without special prior knowledge thanks to the clear examples.
Image reconstruction analysis for positron emission tomography with heterostructured scintillators
(2022)
The concept of structure engineering has been proposed for exploring the next generation of radiation detectors with improved performance. A TOF-PET geometry with heterostructured scintillators with a pixel size of 3.0×3.1×15 mm3 was simulated using Monte Carlo. The heterostructures consisted of alternating layers of BGO as a dense material with high stopping power and plastic (EJ232) as a fast light emitter. The detector time resolution was calculated as a function of the deposited and shared energy in both materials on an event-by-event basis. While sensitivity was reduced to 32% for 100 μm thick plastic layers and 52% for 50 μm, the CTR distribution improved to 204±49 ps and 220±41 ps respectively, compared to 276 ps that we considered for bulk BGO. The complex distribution of timing resolutions was accounted for in the reconstruction. We divided the events into three groups based on their CTR and modeled them with different Gaussian TOF kernels. On a NEMA IQ phantom, the heterostructures had better contrast recovery in early iterations. On the other hand, BGO achieved a better contrast to noise ratio (CNR) after the 15th iteration due to the higher sensitivity. The developed simulation and reconstruction methods constitute new tools for evaluating different detector designs with complex time responses.
A research framework for human aspects in the internet of production: an intra-company perspective
(2020)
Digitalization in the production sector aims at transferring concepts and methods from the Internet of Things (IoT) to the industry and is, as a result, currently reshaping the production area. Besides technological progress, changes in work processes and organization are relevant for a successful implementation of the “Internet of Production” (IoP). Focusing on the labor organization and organizational procedures emphasizes to consider intra-company factors such as (user) acceptance, ethical issues, and ergonomics in the context of IoP approaches. In the scope of this paper, a research approach is presented that considers these aspects from an intra-company perspective by conducting studies on the shop floor, control level and management level of companies in the production area. Focused on four central dimensions—governance, organization, capabilities, and interfaces—this contribution presents a research framework that is focused on a systematic integration and consideration of human aspects in the realization of the IoP.