TY  - JOUR
A1  - Hunker, Jan L.
A1  - Gossmann, Matthias
A1  - Raman, Aravind Hariharan
A1  - Linder, Peter
T1  - Artificial neural networks in cardiac safety assessment: Classification of chemotherapeutic compound effects on hiPSC-derived cardiomyocyte contractility
JF  - Journal of Pharmacological and Toxicological Methods
Y1  - 2021
U6  - http://dx.doi.org/10.1016/j.vascn.2021.107044
SN  - 1056-8719
VL  - 111
IS  - Article number 107044
PB  - Elsevier
CY  - New York
ER  - 
TY  - RPRT
A1  - Stölzle-Feix, Sonja
A1  - Thomas, Ulrich
A1  - Engelstädter, Max
A1  - Goßmann, Matthias
A1  - Linder, Peter
A1  - Staat, Manfred
A1  - Raman, Aravind Hariharan
A1  - Jung, Alexander
A1  - Fertig, Niels
T1  - Plattformtechnologie für kardiale Sicherheitspharmakologie basierend auf teilsynthetischem Herzmuskelgewebe (FLEXcyte) : gemeinsamer FuE-Abschlussbericht aller Partner des Verbundprojektes : Projektlaufzeit: 01.10.2018 bis 30.09.2020
Y1  - 2021
U6  - http://dx.doi.org/10.2314/KXP:1813208581
N1  - Förderkennzeichen BMBF 02P18K020-021
Verbundnummer 01185221
PB  - Nanion Technologies GmbH
CY  - München
ER  - 
TY  - JOUR
A1  - Gossmann, Matthias
A1  - Thomas, Ulrich
A1  - Horváth, András
A1  - Dragicevic, Elena
A1  - Stoelzle-Feix, Sonja
A1  - Jung, Alexander
A1  - Raman, Aravind Hariharan
A1  - Staat, Manfred
A1  - Linder, Peter
T1  - A higher-throughput approach to investigate cardiac contractility in vitro under physiological mechanical conditions
JF  - Journal of Pharmacological and Toxicological Methods
Y1  - 2020
U6  - http://dx.doi.org/10.1016/j.vascn.2020.106843
VL  - 105
IS  - Article 106843
PB  - Elsevier
CY  - New York, NY
ER  - 
TY  - JOUR
A1  - Knox, Ronald
A1  - Bruggemann, Andrea
A1  - Gossmann, Matthias
A1  - Thomas, Ulrich
A1  - Horváth, András
A1  - Dragicevic, Elena
A1  - Stoelzle-Feix, Sonja
A1  - Fertig, Niels
A1  - Jung, Alexander
A1  - Raman, Aravind Hariharan
A1  - Staat, Manfred
A1  - Linder, Peter
T1  - Combining physiological relevance and throughput for in vitro cardiac contractility measurement
JF  - Biophysical Journal
N2  - Despite increasing acceptance of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in safety pharmacology, controversy remains about the physiological relevance of existing in vitro models for their mechanical testing. We hypothesize that existing signs of immaturity of the cell models result from an improper mechanical environment. We cultured hiPSC-CMs in a 96-well format on hyperelastic silicone membranes imitating their native mechanical environment, resulting in physiological responses to compound stimuli.We validated cell responses on the FLEXcyte 96, with a set of reference compounds covering a broad range of cellular targets, including ion channel modulators, adrenergic receptor modulators and kinase inhibitors. Acute (10 - 30 min) and chronic (up to 7 days) effects were investigated. Furthermore, the measurements were complemented with electromechanical models based on electrophysiological recordings of the used cell types.hiPSC-CMs were cultured on freely-swinging, ultra-thin and hyperelastic silicone membranes. The weight of the cell culture medium deflects the membranes downwards. Rhythmic contraction of the hiPSC-CMs resulted in dynamic deflection changes which were quantified by capacitive distance sensing. The cells were cultured for 7 days prior to compound addition. Acute measurements were conducted 10-30 minutes after compound addition in standard culture medium. For chronic treatment, compound-containing medium was replaced daily for up to 7 days. Electrophysiological properties of the employed cell types were recorded by automated patch-clamp (Patchliner) and the results were integrated into the electromechanical model of the system.Calcium channel agonist S Bay K8644 and beta-adrenergic stimulator isoproterenol induced significant positive inotropic responses without additional external stimulation. Kinase inhibitors displayed cardiotoxic effects on a functional level at low concentrations. The system-integrated analysis detected alterations in beating shape as well as frequency and arrhythmic events and we provide a quantitative measure of these.
Y1  - 2020
U6  - http://dx.doi.org/10.1016/j.bpj.2019.11.3104
SN  - 0006-3495
N1  - Raman, Arayind Hariharan 
im Artikel unter dem Namen: Raman, Alexander H.
VL  - 118
IS  - Issue 3, Supplement 1
SP  - 570a
PB  - Elsevier
CY  - Amsterdam
ER  - 
TY  - JOUR
A1  - Linder, Peter
A1  - Beckler, Matthias
A1  - Doerr, Leo
A1  - Stoelzle-Feix, Sonja
A1  - Fertig, Niels
A1  - Jung, Alexander
A1  - Staat, Manfred
A1  - Gossmann, Matthias
T1  - A new in vitro tool to investigate cardiac contractility under physiological mechanical conditions
JF  - Journal of Pharmacological and Toxicological Methods
Y1  - 2019
U6  - http://dx.doi.org/10.1016/j.vascn.2019.05.162
SN  - 1056-8719
VL  - 99
IS  - Article number 106595
PB  - Elsevier
CY  - Amsterdam
ER  - 
TY  - CHAP
A1  - Hunker, Jan
A1  - Jung, Alexander
A1  - Goßmann, Matthias
A1  - Linder, Peter
A1  - Staat, Manfred
ED  - Staat, Manfred
ED  - Erni, Daniel
T1  - Development of a tool to analyze the conduction speed in microelectrode array measurements of cardiac tissue
T2  - 3rd YRA MedTech Symposium 2019 : May 24 / 2019 / FH Aachen
N2  - The discovery of human induced pluripotent stem cells reprogrammed from somatic cells [1] and their ability to differentiate into cardiomyocytes (hiPSC-CMs) has provided a robust platform for drug screening [2]. Drug screenings are essential in the development of new components, particularly for evaluating the potential of drugs to induce life-threatening pro-arrhythmias. Between 1988 and 2009, 14 drugs have been removed from the market for this reason [3]. The microelectrode array (MEA) technique is a robust tool for drug screening as it detects the field potentials (FPs) for the entire cell culture. Furthermore, the propagation of the field potential can be examined on an electrode basis. To analyze MEA measurements in detail, we have developed an open-source tool.
Y1  - 2019
SN  - 978-3-940402-22-6
U6  - http://dx.doi.org/10.17185/duepublico/48750
SP  - 7
EP  - 8
PB  - Universität Duisburg-Essen
CY  - Duisburg
ER  - 
TY  - CHAP
A1  - Suryoputri, Nathania
A1  - Ghaderi, Aydin
A1  - Linder, Peter
A1  - Kotliar, Konstantin
A1  - Göttler, Jens
A1  - Sorg, Christian
A1  - Grimmer, Timo
ED  - Erni, Daniel
ED  - Fischerauer, Alice
ED  - Himmel, Jörg
ED  - Seeger, Thomas
ED  - Thelen, Klaus
T1  - Does hemodynamic response function change in Alzheimer disease?
T2  - 2nd YRA MedTech Symposium 2017 : June 8th - 9th / 2017 / Hochschule Ruhr-West
Y1  - 2017
SN  - 978-3-9814801-9-1
U6  - http://dx.doi.org/10.17185/duepublico/43984
N1  - A young researchers track of the 7th IEEE Workshop & SENSORICA 2017
SP  - 92
PB  - Universität Duisburg-Essen
CY  - Duisburg
ER  - 
TY  - JOUR
A1  - Goßmann, Matthias
A1  - Frotscher, Ralf
A1  - Linder, Peter
A1  - Bayer, Robin
A1  - Epple, U.
A1  - Staat, Manfred
A1  - Temiz Artmann, Aysegül
A1  - Artmann, Gerhard
T1  - Mechano-pharmacological characterization of cardiomyocytes derived from human induced pluripotent stem cells
JF  - Cellular physiology and biochemistry
N2  - Background/Aims: Common systems for the quantification of cellular contraction rely on animal-based models, complex experimental setups or indirect approaches. The herein presented CellDrum technology for testing mechanical tension of cellular monolayers and thin tissue constructs has the potential to scale-up mechanical testing towards medium-throughput analyses. Using hiPS-Cardiac Myocytes (hiPS-CMs) it represents a new perspective of drug testing and brings us closer to personalized drug medication. Methods: In the present study, monolayers of self-beating hiPS-CMs were grown on ultra-thin circular silicone membranes and deflect under the weight of the culture medium. Rhythmic contractions of the hiPS-CMs induced variations of the membrane deflection. The recorded contraction-relaxation-cycles were analyzed with respect to their amplitudes, durations, time integrals and frequencies. Besides unstimulated force and tensile stress, we investigated the effects of agonists and antagonists acting on Ca²⁺ channels (S-Bay K8644/verapamil) and Na⁺ channels (veratridine/lidocaine). Results: The measured data and simulations for pharmacologically unstimulated contraction resembled findings in native human heart tissue, while the pharmacological dose-response curves were highly accurate and consistent with reference data. Conclusion: We conclude that the combination of the CellDrum with hiPS-CMs offers a fast, facile and precise system for pharmacological, toxicological studies and offers new preclinical basic research potential.
KW  - Inotropic compounds
KW  - Pharmacology
KW  - Ion channels
KW  - CellDrum
KW  - Heart tissue culture
KW  - Induced pluripotent stem cells
KW  - Cardiac myocytes
Y1  - 2016
U6  - http://dx.doi.org/10.1159/000443124
SN  - 1421-9778 (Online)
SN  - 1015-8987 (Print)
VL  - 38
IS  - 3
SP  - 1182
EP  - 1198
PB  - Karger
CY  - Basel
ER  - 
TY  - JOUR
A1  - Kowalski, Julia
A1  - Linder, Peter
A1  - Zierke, S.
A1  - Wulfen, B. van
A1  - Clemens, J.
A1  - Konstantinidis, K.
A1  - Ameres, G.
A1  - Hoffmann, R.
A1  - Mikucki, J.
A1  - Tulaczyk, S.
A1  - Funke, O.
A1  - Blandfort, D.
A1  - Espe, Clemens
A1  - Feldmann, Marco
A1  - Francke, Gero
A1  - Hiecker, S.
A1  - Plescher, Engelbert
A1  - Schöngarth, Sarah
A1  - Dachwald, Bernd
A1  - Digel, Ilya
A1  - Artmann, Gerhard
A1  - Eliseev, D.
A1  - Heinen, D.
A1  - Scholz, F.
A1  - Wiebusch, C.
A1  - Macht, S.
A1  - Bestmann, U.
A1  - Reineking, T.
A1  - Zetzsche, C.
A1  - Schill, K.
A1  - Förstner, R.
A1  - Niedermeier, H.
A1  - Szumski, A.
A1  - Eissfeller, B.
A1  - Naumann, U.
A1  - Helbing, K.
T1  - Navigation technology for exploration of glacier ice with maneuverable melting probes
JF  - Cold Regions Science and Technology
N2  - The Saturnian moon Enceladus with its extensive water bodies underneath a thick ice sheet cover is a potential candidate for extraterrestrial life. Direct exploration of such extraterrestrial aquatic ecosystems requires advanced access and sampling technologies with a high level of autonomy. A new technological approach has been developed as part of the collaborative research project Enceladus Explorer (EnEx). The concept is based upon a minimally invasive melting probe called the IceMole. The force-regulated, heater-controlled IceMole is able to travel along a curved trajectory as well as upwards. Hence, it allows maneuvers which may be necessary for obstacle avoidance or target selection. Maneuverability, however, necessitates a sophisticated on-board navigation system capable of autonomous operations. The development of such a navigational system has been the focal part of the EnEx project. The original IceMole has been further developed to include relative positioning based on in-ice attitude determination, acoustic positioning, ultrasonic obstacle and target detection integrated through a high-level sensor fusion. This paper describes the EnEx technology and discusses implications for an actual extraterrestrial mission concept.
Y1  - 2016
U6  - http://dx.doi.org/10.1016/j.coldregions.2015.11.006
SN  - 0165-232X
IS  - 123
SP  - 53
EP  - 70
PB  - Elsevier
CY  - Amsterdam
ER  - 
TY  - JOUR
A1  - Micili, Serap C.
A1  - Valter, Markus
A1  - Oflaz, Hakan
A1  - Ozogul, Candan
A1  - Linder, Peter
A1  - Föckler, Nicole
A1  - Artmann, Gerhard
A1  - Digel, Ilya
A1  - Temiz Artmann, Aysegül
T1  - Optical coherence tomography : a potential tool to predict premature rupture of fetal membranes
JF  - Proceedings of the Institution of Mechanical Engineers. Part H : Journal of engineering in medicine
Y1  - 2013
SN  - 0046-2039 (Print) ; 2041-3033 (E-Journal)
VL  - Vol. 227
IS  - No. 4
SP  - 393
EP  - 401
PB  - Sage
CY  - London
ER  -