TY - JOUR A1 - Molinnus, Denise A1 - Muschallik, Lukas A1 - Gonzalez, Laura Osorio A1 - Bongaerts, Johannes A1 - Wagner, Torsten A1 - Selmer, Thorsten A1 - Siegert, Petra A1 - Keusgen, Michael A1 - Schöning, Michael Josef T1 - Development and characterization of a field-effect biosensor for the detection of acetoin JF - Biosensors and Bioelectronics N2 - 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. Y1 - 2018 U6 - http://dx.doi.org/10.1016/j.bios.2018.05.023 VL - 115 SP - 1 EP - 6 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Molinnus, Denise A1 - Hardt, Gabriel A1 - Siegert, Petra A1 - Willenberg, Holger S. A1 - Poghossian, Arshak A1 - Keusgen, Michael A1 - Schöning, Michael Josef T1 - Detection of Adrenaline in Blood Plasma as Biomarker for Adrenal Venous Sampling JF - Electroanalysis N2 - An amperometric bi-enzyme biosensor based on substrate recycling principle for the amplification of the sensor signal has been developed for the detection of adrenaline in blood. Adrenaline can be used as biomarker verifying successful adrenal venous sampling procedure. The adrenaline biosensor has been realized via modification of a galvanic oxygen sensor with a bi-enzyme membrane combining a genetically modified laccase and a pyrroloquinoline quinone-dependent glucose dehydrogenase. The measurement conditions such as pH value and temperature were optimized to enhance the sensor performance. A high sensitivity and a low detection limit of about 0.5–1 nM adrenaline have been achieved in phosphate buffer at pH 7.4, relevant for measurements in blood samples. The sensitivity of the biosensor to other catecholamines such as noradrenaline, dopamine and dobutamine has been studied. Finally, the sensor has been successfully applied for the detection of adrenaline in human blood plasma. Y1 - 2018 U6 - http://dx.doi.org/10.1002/elan.201800026 SN - 1521-4109 VL - 30 IS - 5 SP - 937 EP - 942 PB - Wiley-VCH CY - Weinheim ER - TY - CHAP A1 - Molinnus, Denise A1 - Hardt, Gabriel A1 - Käver, Larissa A1 - Willenberg, Holger S. A1 - Poghossian, Arshak A1 - Keusgen, Michael A1 - Schöning, Michael Josef T1 - Detection of Adrenaline Based on Bioelectrocatalytical System to Support Tumor Diagnostic Technology T2 - MDPI Proceedings Y1 - 2017 U6 - http://dx.doi.org/10.3390/proceedings1040506 ER - TY - JOUR A1 - Molinnus, Denise A1 - Hardt, G. A1 - Käver, L. A1 - Willenberg, H.S. A1 - Kröger, J.-C. A1 - Poghossian, Arshak A1 - Keusgen, Michael A1 - Schöning, Michael Josef T1 - Chip-based biosensor for the detection of low adrenaline concentrations to support adrenal venous sampling JF - Sensor and Actuators B: Chemical N2 - A chip-based amperometric biosensor referring on using the bioelectrocatalytical amplification principle for the detection of low adrenaline concentrations is presented. The adrenaline biosensor has been prepared by modification of a platinum thin-film electrode with an enzyme membrane containing the pyrroloquinoline quinone-dependent glucose dehydrogenase and glutaraldehyde. Measuring conditions such as temperature, pH value, and glucose concentration have been optimized to achieve a high sensitivity and a low detection limit of about 1 nM adrenaline measured in phosphate buffer at neutral pH value. The response of the biosensor to different catecholamines has also been proven. Long-term stability of the adrenaline biosensor has been studied over 10 days. In addition, the biosensor has been successfully applied for adrenaline detection in human blood plasma for future biomedical applications. Furthermore, preliminary experiments have been carried to detect the adrenaline-concentration difference measured in peripheral blood and adrenal venous blood, representing the adrenal vein sampling procedure of a physician. Y1 - 2018 U6 - http://dx.doi.org/10.1016/j.snb.2018.05.136 SN - 0925-4005 VL - 272 SP - 21 EP - 27 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Molinnus, Denise A1 - Bäcker, Matthias A1 - Iken, Heiko A1 - Poghossian, Arshak A1 - Keusgen, Michael A1 - Schöning, Michael Josef T1 - Concept for a biomolecular logic chip with an integrated sensor and actuator function JF - Physica status solidi (a) N2 - A concept for a new generation of an integrated multi-functional biosensor/actuator system is developed, which is based on biomolecular logic principles. Such a system is expected to be able to detect multiple biochemical input signals simultaneously and in real-time and convert them into electrical output signals with logical operations such as OR, AND, etc. The system can be designed as a closed-loop drug release device triggered by an enzyme logic gate, while the release of the drug induced by the actuator at the required dosage and timing will be controlled by an additional drug sensor. Thus, the system could help to make an accurate and specific diagnosis. The presented concept is exemplarily demonstrated by using an enzyme logic gate based on a glucose/glucose oxidase system, a temperature-responsive hydrogel mimicking the actuator function and an insulin (drug) sensor. In this work, the results of functional testing of individual amperometric glucose and insulin sensors as well as an impedimetric sensor for the detection of the hydrogel swelling/shrinking are presented. Y1 - 2015 U6 - http://dx.doi.org/10.1002/pssa.201431913 SN - 1862-6319 VL - 212 IS - 6 SP - 1382 EP - 1388 PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Kirchner, Patrick A1 - Reisert, Steffen A1 - Pütz, Patrick A1 - Keusgen, Michael A1 - Schöning, Michael Josef T1 - Characterisation of polymeric materials as passivation layer for calorimetric H2O2 gas sensors JF - Physica Status Solidi (a) N2 - Calorimetric gas sensors for monitoring the H₂O₂ concentration at elevated temperatures in industrial sterilisation processes have been presented in previous works. These sensors are built up in form of a differential set-up of a catalytically active and passive temperature-sensitive structure. Although, various types of catalytically active dispersions have been studied, the passivation layer has to be established and therefore, chemically as well as physically characterised. In the present work, fluorinated ethylene propylene (FEP), perfluoralkoxy (PFA) and epoxy-based SU-8 photoresist as temperature-stable polymeric materials have been investigated for sensor passivation in terms of their chemical inertness against H₂O₂, their hygroscopic properties as well as their morphology. The polymeric materials were deposited via spin-coating on the temperature-sensitive structure, wherein spin-coated FEP and PFA show slight agglomerates. However, they possess a low absorption of humidity due to their hydrophobic surface, whereas the SU-8 layer has a closed surface but shows a slightly higher absorption of water. All of them were inert against gaseous H₂O₂ during the characterisation in H₂O₂ atmosphere that demonstrates their suitability as passivation layer for calorimetric H₂O₂ gas sensors. Y1 - 2012 U6 - http://dx.doi.org/10.1002/pssa.201100773 SN - 1862-6319 VL - 209 IS - 5 SP - 859 EP - 863 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Kirchner, Patrick A1 - Oberländer, Jan A1 - Suso, Henri-Pierre A1 - Rysstad, Gunnar A1 - Keusgen, Michael A1 - Schöning, Michael Josef T1 - Towards a wireless sensor system for real-time H2O2 monitoring in aseptic food processes JF - Physica status solidi (a) N2 - A wireless sensor system based on the industrial ZigBee standard for low-rate wireless networking was developed that enables real-time monitoring of gaseous H2O2 during the package sterilization in aseptic food processes. The sensor system consists of a remote unit connected to a calorimetric gas sensor, which was already established in former works, and an external base unit connected to a laptop computer. The remote unit was built up by an XBee radio frequency (RF) module for data communication and a programmable system-on-chip controller to read out the sensor signal and process the sensor data, whereas the base unit is a second XBee RF module. For the rapid H2O2 detection on various locations inside the package that has to be sterilized, a novel read-out strategy of the calorimetric gas sensor was established, wherein the sensor response is measured within the short sterilization time and correlated with the present H2O2 concentration. In an exemplary measurement application in an aseptic filling machinery, the suitability of the new, wireless sensor system was demonstrated, wherein the influence of the gas velocity on the H2O2 distribution inside a package was determined and verified with microbiological tests. KW - calorimetric gas sensor;hydrogen peroxide;wireless sensor system Y1 - 2013 U6 - http://dx.doi.org/10.1002/pssa.201200920 SN - 1862-6319 VL - 210 IS - 5 SP - 877 EP - 883 PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Kirchner, Patrick A1 - Oberländer, Jan A1 - Friedrich, Peter A1 - Berger, Jörg A1 - Suso, Henri-Pierre A1 - Kupyna, Andriy A1 - Keusgen, Michael A1 - Schöning, Michael Josef T1 - Optimisation and fabrication of a calorimetric gas sensor built up on a polyimide substrate for H2O2 monitoring JF - Physica status solidi (a) : applications and material science. 208 (2011), H. 6 Y1 - 2011 SN - 1862-6319 SP - 1235 EP - 1240 PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Kirchner, Patrick A1 - Oberländer, Jan A1 - Friedrich, Peter A1 - Berger, Jörg A1 - Rysstad, Gunnar A1 - Schöning, Michael Josef A1 - Keusgen, Michael T1 - Realisation of a calorimetric gas sensor on polyimide foil for applications in aseptic food industry JF - Sensors and Actuators B: Chemical N2 - A calorimetric gas sensor is presented for the monitoring of vapour-phase H2O2 at elevated temperature during sterilisation processes in aseptic food industry. The sensor was built up on a flexible polyimide foil (thickness: 25 μm) that has been chosen due to its thermal stability and low thermal conductivity. The sensor set-up consists of two temperature-sensitive platinum thin-film resistances passivated by a layer of SU-8 photo resist and catalytically activated by manganese(IV) oxide. Instead of an active heating structure, the calorimetric sensor utilises the elevated temperature of the evaporated H2O2 aerosol. In an experimental test rig, the sensor has shown a sensitivity of 4.78 °C/(%, v/v) in a H2O2 concentration range of 0%, v/v to 8%, v/v. Furthermore, the sensor possesses the same, unchanged sensor signal even at varied medium temperatures between 210 °C and 270 °C of the gas stream. At flow rates of the gas stream from 8 m3/h to 12 m3/h, the sensor has shown only a slightly reduced sensitivity at a low flow rate of 8 m3/h. The sensor characterisation demonstrates the suitability of the calorimetric gas sensor for monitoring the efficiency of industrial sterilisation processes. KW - Sterilisation process KW - Hydrogen peroxide KW - Polyimide KW - Calorimetric gas sensor Y1 - 2012 U6 - http://dx.doi.org/10.1016/j.snb.2011.01.032 SN - 0925-4005 N1 - Part of special issue "Eurosensors XXIV, 2010" VL - 170 SP - 60 EP - 66 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Kirchner, Patrick A1 - Li, Bin A1 - Spelthahn, Heiko A1 - Henkel, Hartmut A1 - Schneider, Andreas A1 - Friedrich, Peter A1 - Kolstad, Jens A1 - Keusgen, Michael A1 - Schöning, Michael Josef T1 - Thin-film calorimetric H2O2 gas sensor for the validation of germicidal effectivity in aseptic filling processes JF - Sensors and Actuators B: Chemical. 154 (2011), H. 2 Y1 - 2011 SN - 1873-3077 N1 - EUROSENSORS XXIII SP - 257 EP - 263 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Keusgen, Michael A1 - Jünger, Martina A1 - Krest, Ingo A1 - Schöning, Michael Josef T1 - Biosensoric detection of the cysteine sulphoxide alliin JF - Sensors and Actuators B. 95 (2003), H. 1-3 Y1 - 2003 SN - 0925-4005 SP - 297 EP - 302 ER - TY - JOUR A1 - Jildeh, Zaid B. A1 - Oberländer, Jan A1 - Kirchner, Patrick A1 - Keusgen, Michael A1 - Wagner, Patrick H. A1 - Schöning, Michael Josef T1 - Experimental and Numerical Analyzes of a Sensor Based on Interdigitated Electrodes for Studying Microbiological Alterations JF - physica status solidi (a): applications and materials science N2 - In this work, a cell-based biosensor to evaluate the sterilization efficacy of hydrogen peroxide vapor sterilization processes is characterized. The transducer of the biosensor is based on interdigitated gold electrodes fabricated on an inert glass substrate. Impedance spectroscopy is applied to evaluate the sensor behavior and the alteration of test microorganisms due to the sterilization process. These alterations are related to changes in relative permittivity and electrical conductivity of the bacterial spores. Sensor measurements are conducted with and without bacterial spores (Bacillus atrophaeus), as well as after an industrial sterilization protocol. Equivalent two-dimensional numerical models based on finite element method of the periodic finger structures of the interdigitated gold electrodes are designed and validated using COMSOL® Multiphysics software by the application of known dielectric properties. The validated models are used to compute the electrical properties at different sensor states (blank, loaded with spores, and after sterilization). As a final result, we will derive and tabulate the frequency-dependent electrical parameters of the spore layer using a novel model that combines experimental data with numerical optimization techniques. Y1 - 2018 U6 - http://dx.doi.org/10.1002/pssa.201700920 SN - 1862-6319 VL - 215 IS - 15 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Jablonski, Melanie A1 - Poghossian, Arshak A1 - Severin, Robin A1 - Keusgen, Michael A1 - Wege, Christian A1 - Schöning, Michael Josef T1 - Capacitive Field-Effect Biosensor Studying Adsorption of Tobacco Mosaic Virus Particles JF - Micromachines N2 - Plant virus-like particles, and in particular, tobacco mosaic virus (TMV) particles, are increasingly being used in nano- and biotechnology as well as for biochemical sensing purposes as nanoscaffolds for the high-density immobilization of receptor molecules. The sensitive parameters of TMV-assisted biosensors depend, among others, on the density of adsorbed TMV particles on the sensor surface, which is affected by both the adsorption conditions and surface properties of the sensor. In this work, Ta₂O₅-gate field-effect capacitive sensors have been applied for the label-free electrical detection of TMV adsorption. The impact of the TMV concentration on both the sensor signal and the density of TMV particles adsorbed onto the Ta₂O₅-gate surface has been studied systematically by means of field-effect and scanning electron microscopy methods. In addition, the surface density of TMV particles loaded under different incubation times has been investigated. Finally, the field-effect sensor also demonstrates the label-free detection of penicillinase immobilization as model bioreceptor on TMV particles. KW - capacitive field-effect sensor KW - plant virus detection KW - tobacco mosaic virus (TMV) KW - TMV adsorption KW - Ta₂O₅ gate Y1 - 2021 U6 - http://dx.doi.org/10.3390/mi12010057 VL - 12 IS - 1 PB - MDPI CY - Basel ER - TY - JOUR A1 - Bronder, Thomas A1 - Poghossian, Arshak A1 - Scheja, Sabrina A1 - Wu, Chunsheng A1 - Keusgen, Michael A1 - Mewes, Dieter A1 - Schöning, Michael Josef T1 - DNA Immobilization and Hybridization Detection by the Intrinsic Molecular Charge Using Capacitive Field-Effect Sensors Modified with a Charged Weak Polyelectrolyte Layer JF - Applied Materials & Interfaces N2 - Miniaturized setup, compatibility with advanced micro- and nanotechnologies, and ability to detect biomolecules by their intrinsic molecular charge favor the semiconductor field-effect platform as one of the most attractive approaches for the development of label-free DNA chips. In this work, a capacitive field-effect EIS (electrolyte–insulator–semiconductor) sensor covered with a layer-by-layer prepared, positively charged weak polyelectrolyte layer of PAH (poly(allylamine hydrochloride)) was used for the label-free electrical detection of DNA (deoxyribonucleic acid) immobilization and hybridization. The negatively charged probe single-stranded DNA (ssDNA) molecules were electrostatically adsorbed onto the positively charged PAH layer, resulting in a preferentially flat orientation of the ssDNA molecules within the Debye length, thus yielding a reduced charge-screening effect and a higher sensor signal. Each sensor-surface modification step (PAH adsorption, probe ssDNA immobilization, hybridization with complementary target DNA (cDNA), reducing an unspecific adsorption by a blocking agent, incubation with noncomplementary DNA (ncDNA) solution) was monitored by means of capacitance–voltage and constant-capacitance measurements. In addition, the surface morphology of the PAH layer was studied by atomic force microscopy and contact-angle measurements. High hybridization signals of 34 and 43 mV were recorded in low-ionic strength solutions of 10 and 1 mM, respectively. In contrast, a small signal of 4 mV was recorded in the case of unspecific adsorption of fully mismatched ncDNA. The density of probe ssDNA and dsDNA molecules as well as the hybridization efficiency was estimated using the experimentally measured DNA immobilization and hybridization signals and a simplified double-layer capacitor model. The results of field-effect experiments were supported by fluorescence measurements, verifying the DNA-immobilization and hybridization event. Y1 - 2015 U6 - http://dx.doi.org/10.1021/acsami.5b05146 VL - 36 IS - 7 SP - 20068 EP - 20075 PB - American Chemical Society CY - Washington, DC ER - TY - JOUR A1 - Bronder, Thomas A1 - Poghossian, Arshak A1 - Keusgen, Michael A1 - Schöning, Michael Josef T1 - Label-free detection of double-stranded DNA molecules with polyelectrolyte-modified capacitive field-effect sensors T1 - Markierungsfreie Detektion doppelsträngiger DNA Moleküle mit Hilfe von Polyelektrolyt-modifizierten kapazitiven Feldeffekt-Sensoren JF - tm - Technisches Messen N2 - 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. Y1 - 2017 U6 - http://dx.doi.org/10.1515/teme-2017-0015 VL - 84 IS - 10 SP - 628 EP - 634 PB - De Gruyter CY - Oldenbourg ER - TY - JOUR A1 - Bronder, Thomas A1 - Poghossian, Arshak A1 - Jessing, Max P. A1 - Keusgen, Michael A1 - Schöning, Michael Josef T1 - Surface regeneration and reusability of label-free DNA biosensors based on weak polyelectrolyte-modified capacitive field-effect structures JF - Biosensors and Bioelectronics Y1 - 2019 U6 - http://dx.doi.org/10.1016/j.bios.2018.11.019 SN - 0956-5663 VL - 126 SP - 510 EP - 517 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Bronder, Thomas A1 - Jessing, Max P. A1 - Poghossian, Arshak A1 - Keusgen, Michael A1 - Schöning, Michael Josef T1 - Detection of PCR-Amplified Tuberculosis DNA Fragments with Polyelectrolyte-Modified Field-Effect Sensors JF - Analytical Chemistry N2 - 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. Y1 - 2018 U6 - http://dx.doi.org/10.1021/acs.analchem.8b01807 SN - 0003-2700 VL - 90 IS - 12 SP - 7747 EP - 7753 PB - ACS Publications CY - Washington, DC ER - TY - JOUR A1 - Arreola, Julio A1 - Oberländer, Jan A1 - Mätzkow, M. A1 - Keusgen, Michael A1 - Schöning, Michael Josef T1 - Surface functionalization for spore-based biosensors with organosilanes JF - Electrochimica Acta N2 - In the present work, surface functionalization of different sensor materials was studied. Organosilanes are well known to serve as coupling agent for biomolecules or cells on inorganic materials. 3-aminopropyltriethoxysilane (APTES) was used to attach microbiological spores time to an interdigitated sensor surface. The functionality and physical properties of APTES were studied on isolated sensor materials, namely silicon dioxide (SiO2) and platinum (Pt) as well as the combined material on sensor level. A predominant immobilization of spores could be demonstrated on SiO2 surfaces. Additionally, the impedance signal of APTES-functionalized biosensor chips has been investigated. Y1 - 2017 U6 - http://dx.doi.org/10.1016/j.electacta.2017.04.157 SN - 0013-4686 VL - 241 SP - 237 EP - 243 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Arreola, Julio A1 - Mätzkow, Malte A1 - Durán, Marlena Palomar A1 - Greeff, Anton A1 - Keusgen, Michael A1 - Schöning, Michael Josef T1 - Optimization of the immobilization of bacterial spores on glass substrates with organosilanes JF - Physica status solidi (A) : Applications and materials science N2 - Spores can be immobilized on biosensors to function as sensitive recognition elements. However, the immobilization can affect the sensitivity and reproducibility of the sensor signal. In this work, three different immobilization strategies with organosilanes were optimized and characterized to immobilize Bacillus atrophaeus spores on glass substrates. Five different silanization parameters were investigated: nature of the solvent, concentration of the silane, silanization time, curing process, and silanization temperature. The resulting silane layers were resistant to a buffer solution (e.g., Ringer solution) with a polysorbate (e.g., Tween®80) and sonication. KW - silanization KW - organosilanes KW - immobilization KW - endospores KW - biosensors KW - Bacillus atrophaeus Y1 - 2016 U6 - http://dx.doi.org/10.1002/pssa.201532914 SN - 1862-6319 VL - 213 IS - 6 SP - 1463 EP - 1470 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Arreola, Julio A1 - Keusgen, Michael A1 - Wagner, Torsten A1 - Schöning, Michael Josef T1 - Combined calorimetric gas- and spore-based biosensor array for online monitoring and sterility assurance of gaseous hydrogen peroxide in aseptic filling machines JF - Biosensors and Bioelectronics Y1 - 2019 U6 - http://dx.doi.org/10.1016/j.bios.2019.111628 SN - 0956-5663 VL - 143 IS - 111628 PB - Elsevier CY - Amsterdam ER -