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In this paper, carbon nanotubes (CNTs) were incorporated in penicillinase-phospholipid Langmuir and Langmuir–Blodgett (LB) films to enhance the enzyme catalytic properties. Adsorption of the penicillinase and CNTs at dimyristoylphosphatidic acid (DMPA) monolayers at the air–water interface was investigated by surface pressure–area isotherms, vibrational spectroscopy, and Brewster angle microscopy. The floating monolayers were transferred to solid supports through the LB technique, forming mixed DMPA-CNTs-PEN films, which were investigated by quartz crystal microbalance, vibrational spectroscopy, and atomic force microscopy. Enzyme activity was studied with UV–vis spectroscopy and the feasibility of the supramolecular device nanostructured as ultrathin films were essayed in a capacitive electrolyte–insulator–semiconductor (EIS) sensor device. The presence of CNTs in the enzyme–lipid LB film not only tuned the catalytic activity of penicillinase but also helped conserve its enzyme activity after weeks, showing increased values of activity. Viability as penicillin sensor was demonstrated with capacitance/voltage and constant capacitance measurements, exhibiting regular and distinctive output signals over all concentrations used in this work. These results may be related not only to the nanostructured system provided by the film, but also to the synergism between the compounds on the active layer, leading to a surface morphology that allowed a fast analyte diffusion because of an adequate molecular accommodation, which also preserved the penicillinase activity. This work therefore demonstrates the feasibility of employing LB films composed of lipids, CNTs, and enzymes as EIS devices for biosensing applications.
The invention pertains to a CellDrum electrode arrangement for measuring mechanical stress, comprising a mechanical holder (1 ) and a non-conductive membrane (4), whereby the membrane (4) is at least partially fixed at its circumference to the mechanical holder (1), keeping it in place when the membrane (4) may bend due to forces acting on the membrane (4), the mechanical holder (1) and the membrane (4) forming a container, whereby the membrane (1) within the container comprises an cell- membrane compound layer or biological material (3) adhered to the deformable membrane 4 which in response to stimulation by an agent may exert mechanical stress to the membrane (4) such that the membrane bending stage changes whereby the container may be filled with an electrolyte, whereby an electric contact (2) is arranged allowing to contact said electrolyte when filled into to the container, whereby within a predefined geometry to the fixing of the membrane (4) an electrode (7) is arranged, whereby the electrode (7) is electrically insulated with respect to the electric contact (2) as well as said electrolyte, whereby mechanical stress due to an agent may be measured as a change in capacitance.
The integration of biomolecular logic principles with electronic transducers allows designing novel digital biosensors with direct electrical output, logically triggered drug-release, and closed-loop sense/act/treat systems. This opens new opportunities for advanced personalized medicine in the context of theranostics. In the present work, we will discuss selected examples of recent developments in the field of interfacing enzyme logic gates with electrodes and semiconductor field-effect devices. Special attention is given to an enzyme OR/Reset logic gate based on a capacitive field-effect electrolyte-insulator-semiconductor sensor modified with a multi-enzyme membrane. Further examples are a digital adrenaline biosensor based on an AND logic gate with binary YES/NO output and an integrated closed-loop sense/act/treat system comprising an amperometric glucose sensor, a hydrogel actuator, and an insulin (drug) sensor.
Cyber-physical systems are ever more common in manufacturing industries. Increasing their autonomy has been declared an explicit goal, for example, as part of the Industry 4.0 vision. To achieve this system intelligence, principled and software-driven methods are required to analyze sensing data, make goal-directed decisions, and eventually execute and monitor chosen tasks. In this chapter, we present a number of knowledge-based approaches to these problems and case studies with in-depth evaluation results of several different implementations for groups of autonomous mobile robots performing in-house logistics in a smart factory. We focus on knowledge-based systems because besides providing expressive languages and capable reasoning techniques, they also allow for explaining how a particular sequence of actions came about, for example, in the case of a failure.
Detection of Adrenaline Based on Bioelectrocatalytical System to Support Tumor Diagnostic Technology
(2017)
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.
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.
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.
Engineers and therefore engineering education are challenged by the increasing complexity of questions to be answered globally. The education of future engineers therefore has to answer with curriculums that build up relevant skills. This chapter will give an example how to bring engineering and social responsibility successful together to build engineers of tomorrow. Through the integration of gender and diversity perspectives, engineering research and teaching is expanded with new perspectives and contents providing an important potential for innovation. Aiming on the enhancement of engineering education with distinctive competencies beyond technical expertise, the teaching approach introduced in the chapter represents key factors to ensure that coming generations of engineers will be able to meet the requirements and challenges a changing globalized world holds for them. The chapter will describe how this approach successfully has been implemented in the curriculum in engineering of a leading technical university in Germany.
Contemporary research appreciates a diverse workforce as a potential source of innovation. Researchers explore the fine details of why diversity management is central for generating innovations in heterogeneous research groups and how it could be effectively implemented into organizations. Complex research associations that discuss topics with a high impact on society increasingly address the necessity of establishing a diverse workforce to confront the challenges of tomorrow. Characterized by complex management structures as well as hierarchies, research associations have not been a subject of investigation until now. For this reason, the presented research project aims to develop a diversity and innovation management strategy with the ultimate goal of inducing change in the corporate culture. The proposed approach consisted of six phases; the first two phases investigated the status quo of diversity in the existing organizational structures of member institutes and the variety of particular working cultures within the research association. The third and the fourth phases utilized qualitative and quantitative studies. The third phase focused on the connection of management level to diversity and innovation, and the need for diversity and innovation management, and tailor-made methods of implementing them. The first three phases have been accomplished successfully; preliminary results are already available. The fourth phase will mainly focus on exploring the mind-set of the employees. The fifth phase will consolidate the findings in the first four phases into an implementable strategy. The final phase will address the implementation of this strategy into the organization. Phases 4 to 6 have not yet been undertaken
An array of four independently wired indium tin oxide (ITO) electrodes was used for electrochemically stimulated DNA release and activation of DNA-based Identity, AND and XOR logic gates. Single-stranded DNA molecules were loaded on the mixed poly(N,N-dimethylaminoethyl methacrylate) (PDMAEMA)/poly(methacrylic acid) (PMAA) brush covalently attached to the ITO electrodes. The DNA deposition was performed at pH 5.0 when the polymer brush is positively charged due to protonation of tertiary amino groups in PDMAEMA, thus resulting in electrostatic attraction of the negatively charged DNA. By applying electrolysis at −1.0 V(vs. Ag/AgCl reference) electrochemical oxygen reduction resulted in the consumption of hydrogen ions and local pH increase near the electrode surface. The process resulted in recharging the polymer brush to the negative state due to dissociation of carboxylic groups of PMAA, thus repulsing the negatively charged DNA and releasing it from the electrode surface. The DNA release was performed in various combinations from different electrodes in the array assembly. The released DNA operated as input signals for activation of the Boolean logic gates. The developed system represents a step forward in DNA computing, combining for the first time DNA chemical processes with electronic input signals.
The telecommunications industry is currently going through a major transformation. In this context, the enhanced Telecom Operations Map (eTOM) is a domain-specific process reference model that is offered by the industry organization TM Forum. In practice, eTOM is well accepted and confirmed as de facto standard. It provides process definitions and process flows on different levels of detail. This article discusses the reference modeling of eTOM, i.e., the design, the resulting artifact, and its evaluation based on three project cases. The application of eTOM in three projects illustrates the design approach and concrete models on strategic and operational levels. The article follows the Design Science Research (DSR) paradigm. It contributes with concrete design artifacts to the transformational needs of the telecommunications industry and offers lessons-learned from a general DSR perspective.
Prior to immobilization of biomolecules or cells onto biosensor surfaces, the surface must be physically or chemically activated for further functionalization. Organosilanes are a versatile option as they facilitate the immobilization through their terminal groups and also display self-assembly. Incorporating hydroxyl groups is one of the important methods for primary immobilization. This can be done, for example, with oxygen plasma treatment. However, this treatment can affect the performance of the biosensors and this effect is not quite well understood for surface functionalization. In this work, the effect of O2 plasma treatment on EIS sensors was investigated by means of electrochemical characterizations: capacitance–voltage (C–V) and constant capacitance (ConCap) measurements. After O2 plasma treatment, the potential of the EIS sensor dramatically shifts to a more negative value. This was successfully reset by using an annealing process.
A graphene-functionalized carbon fiber electrode was modified with adsorbed polyethylenimine to introduce amino functionalities and then with trigonelline and 4-carboxyphenylboronic acid covalently bound to the amino groups. The trigonelline species containing quarterized pyridine groups produced positive charge on the electrode surface regardless of the pH value, while the phenylboronic acid species were neutral below pH 8 and negatively charged above pH 9 (note that their pKa=8.4). The total charge on the monolayer-modified electrode was positive at the neutral pH and negative at pH > 9. Note that 4-carboxyphenylboronic acid was attached to the electrode surface in molar excess to trigonelline, thus allowing the negative charge to dominate on the electrode surface at basic pH. Negatively charged fluorescent dye-labeled insulin (insulin-FITC) was loaded on the modified electrode surface at pH 7.0 due to its electrostatic attraction to the positively charged interface. The local pH in close vicinity to the electrode surface was increased to ca. 9–10 due to consumption of H+ ions upon electrochemical reduction of oxygen proceeding at the potential of −1.0 V (vs. Ag/AgCl) applied on the modified electrode. The process resulted in recharging of the electrode surface to the negative value due to the formation of the negative charge on the phenylboronic acid groups, thus resulting in the electrostatic repulsion of insulin-FITC and stimulating its release from the electrode surface. The insulin release was characterized by fluorescence spectroscopy (using the FITC-labeled insulin), by electrochemical measurements on an iridium oxide, IrOx, electrode and by mass spectrometry. The graphene-functionalized carbon fiber electrode demonstrated significant advantages in the signal-stimulated insulin release comparing with the carbon fiber electrode without the graphene species.
Enzyme-based logic gates and circuits - analytical applications and interfacing with electronics
(2017)
The paper is an overview of enzyme-based logic gates and their short circuits, with specific examples of Boolean AND and OR gates, and concatenated logic gates composed of multi-step enzyme-biocatalyzed reactions. Noise formation in the biocatalytic reactions and its decrease by adding a “filter” system, converting convex to sigmoid response function, are discussed. Despite the fact that the enzyme-based logic gates are primarily considered as components of future biomolecular computing systems, their biosensing applications are promising for immediate practical use. Analytical use of the enzyme logic systems in biomedical and forensic applications is discussed and exemplified with the logic analysis of biomarkers of various injuries, e.g., liver injury, and with analysis of biomarkers characteristic of different ethnicity found in blood samples on a crime scene. Interfacing of enzyme logic systems with modified electrodes and semiconductor devices is discussed, giving particular attention to the interfaces functionalized with signal-responsive materials. Future perspectives in the design of the biomolecular logic systems and their applications are discussed in the conclusion.
This paper presents the results of an eigenvalue analysis of the Fatih Sultan Mehmet Bridge. A high-resolution finite element model was created directly from the available design documents. All physical properties of the structural components were included in detail, so no calibration to the measured data was necessary. The deck and towers were modeled with shell elements. A nonlinear static analysis was performed before the eigenvalue calculation. The calculated natural frequencies and corresponding mode shapes showed good agreement with the available measured ambient vibration data. The calculation of the effective modal mass showed that nine modes had single contributions higher than 5 % of the total mass. They were in a frequency range up to 1.2 Hz. The comparison of the results for the torsional modes especially demonstrated the advantage of using thin shell finite elements over the beam modeling approach.
A physically coupled finite element method (FEM) model is developed to study the response behavior of a calorimetric gas sensor. The modeled sensor serves as a monitoring device of the concentration of gaseous hydrogen peroxide (H2 O2) in a high temperature mixture stream in aseptic sterilization processes. The principle of operation of a calorimetric H2 O2 sensor is analyzed and the results of the numerical model have been validated by using previously published sensor experiments. The deviation in the results between the FEM model and experimental data are presented and discussed.
Genetically humanized mice for proteins involved in drug metabolism and toxicity and mice engrafted with human hepatocytes are emerging as promising in vivo models for improved prediction of the pharmacokinetic, drug–drug interaction, and safety characteristics of compounds in humans. This is an overview on the genetically humanized and chimeric liver-humanized mouse models, which are illustrated with examples of their utility in drug metabolism and toxicity studies. The models are compared to give guidance for selection of the most appropriate model by highlighting advantages and disadvantages to be carefully considered when used for studies in drug discovery and development.
Hotelling’s T² tests in paired and independent survey samples are compared using the traditional asymptotic efficiency concepts of Hodges–Lehmann, Bahadur and Pitman, as well as through criteria based on the volumes of corresponding confidence regions. Conditions characterizing the superiority of a procedure are given in terms of population canonical correlation type coefficients. Statistical tests for checking these conditions are developed. Test statistics based on the eigenvalues of a symmetrized sample cross-covariance matrix are suggested, as well as test statistics based on sample canonical correlation type coefficients.
The link between diversity and innovation is broadly discussed in the context of research and innovation processes. Many institutions and enterprises, specifically in commerce, have already tried to establish sustainable diversity management concepts, in order to increase the diversity of their workforce in addition to establishing a corporate culture of openness. Alongside the creation of a working place where different experiences and skills are valued equally, the entrepreneurial intention is to transfer diversity into economically relevant advantages. Taking into account the potential of diversity in research and innovation processes, the project “Diversity- and Innovation Management” was incorporated within a large interdisciplinary research Cluster. The project’s purpose was to study the context between diversity and innovation in research associations and to later develop a customised management concept into an interdisciplinary research Cluster on integrative production technology with full integration. The challenge of such research associations lays in an organisational structure which is often described as being decentralised. Researchers coming from different academic disciplines, while having diverse habits, conduct research on large scientific issues and challenges. In addition, these researchers are socialised in different institutions and university chairs. Theses differences in leadership styles, business cultures and organisational strategies, follow into their research team work. Taking a closer look into the management of human resources suggests that decentral organised recruitment processes, as well as allocation of human resources, lead to a lacking overview in regard to missing competencies, perspectives and backgrounds in research networks. These circumstances are comparable to big corporate groups. While developing a management concept for research associations, these characteristics must be considered. To ensure this, the project follows a human-centred approach, which considers top-down, as well as bottom-up perspectives. This paper presents the applied mixed-method approach in the scientific issue described above. In the frame of the Cluster of Excellence “Integrative Production Technology for High-Wage Countries” research results based on quantitative, as well as qualitative studies, were presented as an application example. This paper provides a new perspective on the innovation and diversity context. Against the background of complex research organisations, the development approach of a management concept is particularly interesting.
Acknowledging that a diverse workforce could be a potential source of innovation, the current research deals with the fine details of why diversity management is central to achieving innovation in heterogeneous research groups and how this could be effectively realized in an organization. The types of heterogeneities addressed mainly include gender, qualification, academic discipline and intercultural perspectives. The type of organization being dealt with in this work is a complex association of research institutes at a technical university in Germany (RWTH Aachen University), namely a 'Cluster of Excellence', whereby several institutes of the university work collaboratively in different sub-projects. The 'Cluster of Excellence' is a part of the 'Excellence Initiative' of the German federal and state governments German Research Foundation (DFG) and German Council of Science and Humanities, with the ultimate aim of promoting cutting-edge research. To support interdisciplinary collaboration and thus the performance of the cluster, the development of a diversity and innovation management concept is presently in the conceptual phase and will be described in the frame of this paper. The 3-S-Diversity Model, composed of the three elements: skills, structure and strategy, serves as a basis for the development of the concept. The proposed concept consists of six phases; the first two phases lay the ground work by developing an understanding of the status quo on the forms of diversity in the Cluster of Excellence, the type of organizational structure of the member institutes and the varieties of specialist work cultures of the same. The third and the fourth phases build up on this foundation by means of qualitative and quantitative studies. While the third phase deals with the sensitization of the management level to the close connection between diversity and innovation; the need to manage them thereafter and find tailor-made methods of doing so, the fourth phase shall mainly focus on the mindset of the employees in this regard. The fifth phase shall consolidate the learnings and the ideas developed in the course of the first four phases into an implementable strategy. The ultimate phase shall be the implementation of this concept in the Cluster. The first three phases have been accomplished successfully and the preliminary results are already available.
Control mechanisms like Industrial Controls Systems (ICS) and its subgroup SCADA (Supervisory Control and Data Acquisition) are a prerequisite to automate industrial processes. While protection of ICS on process management level is relatively straightforward – well known office IT security mechanisms can be used – protection on field bus level is harder to achieve as there are real-time and production requirements like 24x7 to consider. One option to improve security on field bus level is to introduce controls that help to detect and to react on attacks. This paper introduces an initial set of intrusion detection mechanisms for the field bus protocol EtherCAT. To this end existing Ethernet attack vectors including packet injection and man-in-the-middle attacks are tested in an EtherCAT environment, where they could interrupt the EtherCAT network and may even cause physical damage. Based on the signatures of such attacks, a preprocessor and new rule options are defined for the open source intrusion detection system Snort demonstrating the general feasibility of intrusion detection on field bus level.
Investigation Of The Seismic Behaviour Of Infill Masonry Using Numerical Modelling Approaches
(2017)
Masonry is a widely spread construction type which is used all over the world for different types of structures. Due to its simple and cheap construction, it is used as non-structural as well as structural element. In frame structures, such as
reinforced concrete frames, masonry may be used as infill. While the bare frame itself is able to carry the loads when it comes to seismic events, the infilled frame is not able to warp freely due to the constrained movement. This restraint results in a complex interaction between the infill and the surrounding frame, which may lead to severe damage to the infill as well as the surrounding frame. The interaction is studied in different projects and effective approaches for the description of the behavior are still lacking. Experimental programs are usually quite expensive, while numerical models, once validated, do offer an efficient approach for the investigation of the interaction when horizontally loaded. In order to study the numerous parameters influencing the seismic load bearing behavior, numerical models may be used. Therefore, this contribution presents a numerical approach for the simulation of infill masonry in reinforced concrete frames. Both parts, the surrounding frame as well as the infill are represented by micro modelling approaches to correctly take into account the different types of failure. The adopted numerical model describes the inelastic behavior of the system, as indicated by the obtained results of the overall structural response as well as the formation of damage in the infilled wall. Comparison of the numerical and experimental results highlights the valuable contribution of numerical simulations in the study and design of infilled frames. As damage of the infill masonry may occur in-plane due to the interaction as well as out-of-plane due to the low vertical load, both directions of loading are investigated.
In this study, polyelectrolyte-modified field-effect-based electrolyte-insulator-semiconductor (EIS) devices have been used for the label-free electrical detection of double-stranded deoxyribonucleic acid (dsDNA)molecules. The sensor-chip functionalization with a positively charged polyelectrolyte layer provides the possibility of direct adsorptive binding of negatively charged target DNA oligonucleotides onto theSiO2-chip surface.EIS sensors can be utilized as a tool to detect surface-charge changes; the electrostatic adsorption of oligonucleotides onto the polyelectrolyte layer leads to a measureable surface-potential change. Signals of 39mV have been recorded after the incubation with the oligonucleotide solution. Besides the electrochemical experiments, the successful adsorption of dsDNA onto the polyelectrolyte layer has been verified via fluorescence microscopy. The presented results demonstrate that the signal recording of EISchips, which are modified with a polyelectrolyte layer, canbe used as a favorable approach for a fast, cheap and simple detection method for dsDNA.