TY - CHAP A1 - Frotscher, Ralf A1 - Staat, Manfred ED - Artmann, Gerhard ED - Temiz Artmann, Aysegül ED - Zhubanova, Azhar A. ED - Digel, Ilya T1 - Towards Patient-Specific Computational Modeling of hiPS-Derived Cardiomyocyte Function and Drug Action T2 - Biological, Physical and Technical Basics of Cell Engineering N2 - Human-induced pluripotent stem cell-derived cardiomyocytes (hiPS-CM) today are widely used for the investigation of normal electromechanical cardiac function, of cardiac medication and of mutations. Computational models are thus established that simulate the behavior of this kind of cells. This section first motivates the modeling of hiPS-CM and then presents and discusses several modeling approaches of microscopic and macroscopic constituents of human-induced pluripotent stem cell-derived and mature human cardiac tissue. The focus is led on the mapping of the computational results one can achieve with these models onto mature human cardiomyocyte models, the latter being the real matter of interest. Model adaptivity is the key feature that is discussed because it opens the way for modeling various biological effects like biological variability, medication, mutation and phenotypical expression. We compare the computational with experimental results with respect to normal cardiac function and with respect to inotropic and chronotropic drug effects. The section closes with a discussion on the status quo of the specificity of computational models and on what challenges have to be solved to reach patient-specificity. Y1 - 2018 SN - 978-981-10-7904-7 U6 - http://dx.doi.org/10.1007/978-981-10-7904-7_10 SP - 233 EP - 250 PB - Springer CY - Singapore ER - TY - CHAP A1 - Duong, Minh Tuan A1 - Seifarth, Volker A1 - Temiz Artmann, Aysegül A1 - Artmann, Gerhard A1 - Staat, Manfred ED - Artmann, Gerhard ED - Temiz Artmann, Aysegül ED - Zhubanova, Azhar A. ED - Digel, Ilya T1 - Growth Modelling Promoting Mechanical Stimulation of Smooth Muscle Cells of Porcine Tubular Organs in a Fibrin-PVDF Scaffold T2 - Biological, Physical and Technical Basics of Cell Engineering N2 - Reconstructive surgery and tissue replacements like ureters or bladders reconstruction have been recently studied, taking into account growth and remodelling of cells since living cells are capable of growing, adapting, remodelling or degrading and restoring in order to deform and respond to stimuli. Hence, shapes of ureters or bladders and their microstructure change during growth and these changes strongly depend on external stimuli such as training. We present the mechanical stimulation of smooth muscle cells in a tubular fibrin-PVDFA scaffold and the modelling of the growth of tissue by stimuli. To this end, mechanotransduction was performed with a kyphoplasty balloon catheter that was guided through the lumen of the tubular structure. The bursting pressure was examined to compare the stability of the incubated tissue constructs. The results showed the significant changes on tissues with training by increasing the burst pressure as a characteristic mechanical property and the smooth muscle cells were more oriented with uniformly higher density. Besides, the computational growth models also exhibited the accurate tendencies of growth of the cells under different external stimuli. Such models may lead to design standards for the better layered tissue structure in reconstructing of tubular organs characterized as composite materials such as intestines, ureters and arteries. KW - Mechanical simulation KW - Growth modelling KW - Ureter KW - Bladder KW - Reconstruction Y1 - 2018 SN - 978-981-10-7904-7 U6 - http://dx.doi.org/10.1007/978-981-10-7904-7_9 SP - 209 EP - 232 PB - Springer CY - Singapore ER - TY - CHAP A1 - Staat, Manfred A1 - Heitzer, Michael ED - Staat, Manfred ED - Heitzer, Michael T1 - Probabilistic limit and shakedown problems T2 - Numerical methods for limit and shakedown analysis. Deterministic and probabilistic problems Y1 - 2003 SN - 3-00-010001-6 N1 - NIC Series VL - 15 SP - 217 EP - 268 PB - John von Neumann Institute for Computing (NIC) CY - Jülich ER - TY - CHAP A1 - Bhattarai, Aroj A1 - Staat, Manfred ED - Fernandes, P.R. ED - Tavares, J. M. T1 - Pectopexy to repair vaginal vault prolapse: a finite element approach T2 - Proceedings CMBBE 2018 N2 - The vaginal prolapse after hysterectomy (removal of the uterus) is often associated with the prolapse of the vaginal vault, rectum, bladder, urethra or small bowel. Minimally invasive surgery such as laparoscopic sacrocolpopexy and pectopexy are widely performed for the treatment of the vaginal prolapse with weakly supported vaginal vault after hysterectomy using prosthetic mesh implants to support (or strengthen) lax apical ligaments. Implants of different shape, size and polymers are selected depending on the patient’s anatomy and the surgeon’s preference. In this computational study on pectopexy, DynaMesh®-PRP soft, GYNECARE GYNEMESH® PS Nonabsorbable PROLENE® soft and Ultrapro® are tested in a 3D finite element model of the female pelvic floor. The mesh model is implanted into the extraperitoneal space and sutured to the vaginal stump with a bilateral fixation to the iliopectineal ligament at both sides. Numerical simulations are conducted at rest, after surgery and during Valsalva maneuver with weakened tissues modeled by reduced tissue stiffness. Tissues and prosthetic meshes are modeled as incompressible, isotropic hyperelastic materials. The positions of the organs are calculated with respect to the pubococcygeal line (PCL) for female pelvic floor at rest, after repair and during Valsalva maneuver using the three meshes. Y1 - 2018 N1 - 15th International Symposium on Computer Methods in Biomechanics and Biomedical Engineering and 3rd Conference on Imaging and Visualization. CMBBE 2018. 26-29 March 2018, Lisbon, Portugal ER - TY - JOUR A1 - Poghossian, Arshak A1 - Jablonski, Melanie A1 - Koch, Claudia A1 - Bronder, Thomas A1 - Rolka, David A1 - Wege, Christina A1 - Schöning, Michael Josef T1 - Field-effect biosensor using virus particles as scaffolds for enzyme immobilization JF - Biosensors and Bioelectronics N2 - 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. Y1 - 2018 U6 - http://dx.doi.org/10.1016/j.bios.2018.03.036 SN - 0956-5663 VL - 110 SP - 168 EP - 174 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 - JOUR A1 - Birgel, Stefan A1 - Leschinger, Tim A1 - Wegmann, Kilian A1 - Staat, Manfred T1 - Calculation of muscle forces and joint reaction loads in the shoulder area via an OpenSim based computer model JF - tm - Technisches Messen N2 - Using the OpenSim software and verified anatomical data, a computer model for the calculation of biomechanical parameters is developed and used to determine the effect of a reattachment of the Supraspinatus muscle with a medial displacement of the muscle attachment point, which may be necessary for a rupture of the supraspinatus tendon. The results include the influence of the operation on basic biomechanical parameters such as the lever arm, as well as the calculated the muscle activations for the supraspinatus and deltoid. In addition, the influence on joint stability is examined by an analysis of the joint reaction force. The study provides a detailed description of the used model, as well as medical findings to a reattachment of the supraspinatus. Mit der Software OpenSim und überprüften anatomischen Daten wird ein Computermodell zur Berechnung von biomechanischen Parametern entwickelt und genutzt, um den Effekt einer Refixierung des Supraspinatusmuskels mit einer medialen Verschiebung des Muskelansatzpunktes zu ermitteln, wie sie unter anderem nach einem Riss der Supraspinatussehne notwendig sein kann. Die Ergebnisse umfassen hierbei den Einfluss der Operation auf grundlegende biomechanische Parameter wie den Hebelarm sowie die berechneten Muskelaktivierungen für den Supraspinatus und Deltoideus. Zusätzlich wird der Einfluss auf die Gelenkstabilität betrachtet und durch eine Analyse der Gelenkreaktionskraft untersucht. Die Studie bietet eine detaillierte Beschreibung des genutzten Modells, sowie medizinische Erkenntnisse zu einer Refixierung des Supraspinatus. Y1 - 2018 U6 - http://dx.doi.org/10.1515/teme-2017-0114 SN - 2196-7113 VL - 85 IS - 5 SP - 321 EP - 330 PB - De Gruyter CY - Berlin ER - TY - JOUR A1 - Bhattarai, Aroj A1 - Jabbari, Medisa A1 - Anding, Ralf A1 - Staat, Manfred T1 - Surgical treatment of vaginal vault prolapse using different prosthetic mesh implants: a finite element analysis JF - tm - Technisches Messen N2 - Particularly multiparous elderly women may suffer from vaginal vault prolapse after hysterectomy due to weak support from lax apical ligaments. A decreased amount of estrogen and progesterone in older age is assumed to remodel the collagen thereby reducing tissue stiffness. Sacrocolpopexy is either performed as open or laparoscopic surgery using prosthetic mesh implants to substitute lax ligaments. Y-shaped mesh models (DynaMesh, Gynemesh, and Ultrapro) are implanted in a 3D female pelvic floor finite element model in the extraperitoneal space from the vaginal cuff to the first sacral (S1) bone below promontory. Numerical simulations are conducted during Valsalva maneuver with weakened tissues modeled by reduced tissue stiffness. Tissues are modeled as incompressible, isotropic hyperelastic materials whereas the meshes are modeled either as orthotropic linear elastic or as isotropic hyperlastic materials. The positions of the vaginal cuff and the bladder base are calculated from the pubococcygeal line for female pelvic floor at rest, for prolapse and after repair using the three meshes. Due to mesh mechanics and mesh pore deformation along the loaded direction, the DynaMesh with regular rectangular mesh pores is found to provide better mechanical support to the organs than the Gynemesh and the Ultrapro with irregular hexagonal mesh pores. Insbesondere ältere, mehrgebährende Frauen leiden häufiger an einem Scheidenvorfall nach einer Hysterektomie aufgrund der schwachen Unterstützung durch laxe apikale Bänder. Es wird angenommen, dass eine verringerte Menge an Östrogen und Progesteron im höheren Alter das Kollagen umformt, wodurch die Gewebesteifigkeit reduziert wird. Die Sakrokolpopexie ist eine offene oder laparoskopische Operation, die mit prothetischen Netzimplantaten durchgeführt wird, um laxe Bänder zu ersetzen. Y-förmige Netzmodelle (DynaMesh, Gynemesh und Ultrapro) werden in einem 3D-Modell des weiblichen Beckenbodens im extraperitonealen Raum vom Vaginalstumpf bis zum Promontorium implantiert. Numerische Simulationen werden während des Valsalva-Manövers mit geschwächtem Gewebe durchgeführt, das durch eine reduzierte Gewebesteifigkeit modelliert wird. Die Gewebe werden als inkompressible, isotrop hyperelastische Materialien modelliert, während die Netze entweder als orthotrope linear elastische oder als isotrope hyperlastische Materialien modelliert werden. Die Positionen des Vaginalstumpfs, der Blase und der Harnröhrenachse werden anhand der Pubococcygeallinie aus der Ruhelage, für den Prolaps und nach der Reparatur unter Verwendung der drei Netze berechnet. Aufgrund der Netzmechanik und der Netzporenverformung bietet das DynaMesh mit regelmäßigen rechteckigen Netzporen eine bessere mechanische Unterstützung und eine Neupositionierung des Scheidengewölbes, der Blase und der Urethraachse als Gynemesh und Ultrapro mit unregelmäßigen hexagonalen Netzporen. Y1 - 2018 U6 - http://dx.doi.org/10.1515/teme-2017-0115 SN - 2196-7113 VL - 85 IS - 5 SP - 331 EP - 342 PB - De Gruyter CY - Berlin ER - TY - JOUR A1 - Bhattarai, Aroj A1 - Staat, Manfred T1 - Modelling of Soft Connective Tissues to Investigate Female Pelvic Floor Dysfunctions JF - Computational and Mathematical Methods in Medicine N2 - After menopause, decreased levels of estrogen and progesterone remodel the collagen of the soft tissues thereby reducing their stiffness. Stress urinary incontinence is associated with involuntary urine leakage due to pathological movement of the pelvic organs resulting from lax suspension system, fasciae, and ligaments. This study compares the changes in the orientation and position of the female pelvic organs due to weakened fasciae, ligaments, and their combined laxity. A mixture theory weighted by respective volume fraction of elastin-collagen fibre compound (5%), adipose tissue (85%), and smooth muscle (5%) is adopted to characterize the mechanical behaviour of the fascia. The load carrying response (other than the functional response to the pelvic organs) of each fascia component, pelvic organs, muscles, and ligaments are assumed to be isotropic, hyperelastic, and incompressible. Finite element simulations are conducted during Valsalva manoeuvre with weakened tissues modelled by reduced tissue stiffness. A significant dislocation of the urethrovesical junction is observed due to weakness of the fascia (13.89 mm) compared to the ligaments (5.47 mm). The dynamics of the pelvic floor observed in this study during Valsalva manoeuvre is associated with urethral-bladder hypermobility, greater levator plate angulation, and positive Q-tip test which are observed in incontinent females. Y1 - 2018 U6 - http://dx.doi.org/10.1155/2018/9518076 SN - 1748-6718 VL - 2018 IS - Article ID 9518076 SP - 1 EP - 16 PB - Hindawi CY - New York, NY ER - TY - CHAP A1 - Schmidts, Oliver A1 - Boltes, Maik A1 - Kraft, Bodo A1 - Schreiber, Marc T1 - Multi-pedestrian tracking by moving Bluetooth-LE beacons and stationary receivers T2 - 2017 International Conference on Indoor Positioning and Indoor Navigation (IPIN), 18-21 September 2017, Sapporo, Japan Y1 - 2017 N1 - International Conference on Indoor Positioning and Indoor Navigation <8, 2017, Sapporo, Japan> SP - 1 EP - 4 ER - TY - CHAP A1 - Bhattarai, Aroj A1 - Frotscher, Ralf A1 - Staat, Manfred T1 - Computational Analysis of Pelvic Floor Dysfunction T2 - Women's Health and Biomechanics N2 - Pelvic floor dysfunction (PFD) is characterized by the failure of the levator ani (LA) muscle to maintain the pelvic hiatus, resulting in the descent of the pelvic organs below the pubococcygeal line. This chapter adopts the modified Humphrey material model to consider the effect of the muscle fiber on passive stretching of the LA muscle. The deformation of the LA muscle subjected to intra-abdominal pressure during Valsalva maneuver is compared with the magnetic resonance imaging (MRI) examination of a nulliparous female. Numerical result shows that the fiber-based Humphrey model simulates the muscle behavior better than isotropic constitutive models. Greater posterior movement of the LA muscle widens the levator hiatus due to lack of support from the anococcygeal ligament and the perineal structure as a consequence of birth-related injury and aging. Old and multiparous females with uncontrolled urogenital and rectal hiatus tend to develop PFDs such as prolapse and incontinence. KW - Pelvic muscle KW - Muscle fibers KW - Passive stretching KW - Pelvic floor dysfunction Y1 - 2018 SN - 978-3-319-71574-2 U6 - http://dx.doi.org/10.1007/978-3-319-71574-2_17 N1 - Lecture Notes in Computational Vision and Biomechanics, vol 29 SP - 217 EP - 230 PB - Springer CY - Cham ER - TY - JOUR A1 - Oberländer, Jan A1 - Mayer, Marlena A1 - Greeff, Anton A1 - Keusgen, Michael A1 - Schöning, Michael Josef T1 - Spore-based biosensor to monitor the microbicidal efficacy of gaseous hydrogen peroxide sterilization processes JF - Biosensors and Bioelectronics N2 - In this work, a spore-based biosensor is evaluated to monitor the microbicidal efficacy of sterilization processes applying gaseous hydrogen peroxide (H2O2). The sensor is based on interdigitated electrode structures (IDEs) that have been fabricated by means of thin-film technologies. Impedimetric measurements are applied to study the effect of sterilization process on spores of Bacillus atrophaeus. This resilient microorganism is commonly used in industry to proof the sterilization efficiency. The sensor measurements are accompanied by conventional microbiological challenge tests, as well as morphological characterizations with scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The sensor measurements are correlated with the microbiological test routines. In both methods, namely the sensor-based and microbiological one, a tailing effect has been observed. The results are evaluated and discussed in a three-dimensional calibration plot demonstrating the sensor's suitability to enable a rapid process decision in terms of a successfully performed sterilization. Y1 - 2018 U6 - http://dx.doi.org/10.1016/j.bios.2017.12.045 SN - 0956-5663 VL - 104 SP - 87 EP - 94 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Breuer, Lars A1 - Mang, Thomas A1 - Schöning, Michael Josef A1 - Thoelen, Ronald A1 - Wagner, Torsten T1 - Investigation of the spatial resolution of a laser-based stimulation process for light-addressable hydrogels with incorporated graphene oxide by means of IR thermography JF - Sensors and Actuators A: Physical Y1 - 2017 U6 - http://dx.doi.org/10.1016/j.sna.2017.11.031 SN - 0924-4247 VL - 268 SP - 126 EP - 132 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Kotliar, Konstantin A1 - Hauser, Christine A1 - Ortner, Marion A1 - Muggenthaler, Claudia A1 - Diehl-Schmid, Janine A1 - Angermann, Susanne A1 - Hapfelmeier, Alexander A1 - Schmaderer, Christoph A1 - Grimmer, Timo T1 - Altered neurovascular coupling as measured by optical imaging: a biomarker for Alzheimer’s disease JF - Scientific Reports Y1 - 2017 U6 - http://dx.doi.org/10.1038/s41598-017-13349-5 SN - 2045-2322 N1 - Article 12906 VL - 7 IS - 1 SP - 1 EP - 11 PB - Springer Nature CY - Cham ER - TY - JOUR A1 - Garibaldi, F. A1 - Beging, Stefan A1 - Canese, R. A1 - Carpinelli, G. A1 - Clinthorne, N. A1 - Colilli, S. A1 - Cosentino, L. A1 - Finocchiaro, P. A1 - Giuliani, F. A1 - Gricia, M. A1 - Lucentini, M. A1 - Majewski, S. A1 - Monno, E. A1 - Musico, P. A1 - Santavenere, F. A1 - Tödter, J. A1 - Wegener, Hans-Peter A1 - Ziemons, Karl T1 - A novel TOF-PET MRI detector for diagnosis and follow up of the prostate cancer JF - European Physical Journal Plus Y1 - 2017 U6 - http://dx.doi.org/10.1140/epjp/i2017-11662-x SN - 2190-5444 VL - 132 IS - 9 PB - Springer CY - Berlin ER - TY - GEN A1 - Hackl, Michael A1 - Wegmann, Kilian A1 - Kahmann, Stephanie Lucina A1 - Heinze, Nicolai A1 - Staat, Manfred A1 - Neiss, Wolfram F. A1 - Scaal, Martin A1 - Müller, Lars P. T1 - Reply to the letter to the editor: shortening osteotomy of the proximal radius T2 - Knee Surgery, Sports Traumatology, Arthroscopy Y1 - 2017 U6 - http://dx.doi.org/10.1007/s00167-017-4666-8 VL - 25 IS - 10 SP - 3328 EP - 3329 ER - TY - CHAP A1 - Breuer, Lars A1 - Guthmann, Eric A1 - Schöning, Michael Josef A1 - Thoelen, Ronald A1 - Wagner, Torsten T1 - Light-Stimulated Hydrogels with Incorporated Graphene Oxide as Actuator Material for Flow Control in Microfluidic Applications T2 - Proceedings Eurosensors 2017 Conference, Paris, France, 3–6 September 2017 Y1 - 2017 U6 - http://dx.doi.org/10.3390/proceedings1040524 SP - 1 EP - 4 ER - TY - JOUR A1 - Albanna, Walid A1 - Lueke, Jan Niklas A1 - Sjapic, Volha A1 - Kotliar, Konstantin A1 - Hescheler, Jürgen A1 - Clusmann, Hans A1 - Sjapic, Sergej A1 - Alpdogan, Serdan A1 - Schneider, Toni A1 - Schubert, Gerrit Alexander A1 - Neumaier, Felix T1 - Electroretinographic Assessment of Inner Retinal Signaling in the Isolated and Superfused Murine Retina JF - Current Eye Research Y1 - 2017 U6 - http://dx.doi.org/10.1080/02713683.2017.1339807 SN - 1460-2202 IS - Article in press SP - 1 EP - 9 PB - Taylor & Francis CY - London ER - TY - JOUR A1 - Pilas, Johanna A1 - Yazici, Yasemen A1 - Selmer, Thorsten A1 - Keusgen, Michael A1 - Schöning, Michael Josef T1 - Optimization of an amperometric biosensor array for simultaneous measurement of ethanol, formate, d- and l-lactate JF - Electrochimica Acta N2 - 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. KW - Simultaneous determination KW - Enzymatic biosensor KW - Diaphorase KW - Dehydrogenase Y1 - 2017 U6 - http://dx.doi.org/10.1016/j.electacta.2017.07.119 SN - 0013-4686 VL - 251 SP - 256 EP - 262 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Röhlen, Desiree A1 - Pilas, Johanna A1 - Schöning, Michael Josef A1 - Selmer, Thorsten T1 - Development of an amperometric biosensor platform for the combined determination of l-Malic, Fumaric, and l-Aspartic acid JF - Applied Biochemistry and Biotechnology N2 - 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. Y1 - 2017 U6 - http://dx.doi.org/10.1007/s12010-017-2578-1 SN - 1559-0291 VL - 183 SP - 566 EP - 581 PB - Springer CY - Berlin ER -