@article{HunkerGossmannRamanetal.2021, author = {Hunker, Jan L. and Gossmann, Matthias and Raman, Aravind Hariharan and Linder, Peter}, title = {Artificial neural networks in cardiac safety assessment: Classification of chemotherapeutic compound effects on hiPSC-derived cardiomyocyte contractility}, series = {Journal of Pharmacological and Toxicological Methods}, volume = {111}, journal = {Journal of Pharmacological and Toxicological Methods}, number = {Article number 107044}, publisher = {Elsevier}, address = {New York}, issn = {1056-8719}, doi = {10.1016/j.vascn.2021.107044}, year = {2021}, language = {en} } @techreport{StoelzleFeixThomasEngelstaedteretal.2021, author = {St{\"o}lzle-Feix, Sonja and Thomas, Ulrich and Engelst{\"a}dter, Max and Goßmann, Matthias and Linder, Peter and Staat, Manfred and Raman, Aravind Hariharan and Jung, Alexander and Fertig, Niels}, title = {Plattformtechnologie f{\"u}r kardiale Sicherheitspharmakologie basierend auf teilsynthetischem Herzmuskelgewebe (FLEXcyte) : gemeinsamer FuE-Abschlussbericht aller Partner des Verbundprojektes : Projektlaufzeit: 01.10.2018 bis 30.09.2020}, publisher = {Nanion Technologies GmbH}, address = {M{\"u}nchen}, doi = {10.2314/KXP:1813208581}, pages = {IV, 85 Seiten, 2 ungez{\"a}hlte Seiten}, year = {2021}, language = {de} } @article{GossmannThomasHorvathetal.2020, author = {Gossmann, Matthias and Thomas, Ulrich and Horv{\´a}th, Andr{\´a}s and Dragicevic, Elena and Stoelzle-Feix, Sonja and Jung, Alexander and Raman, Aravind Hariharan and Staat, Manfred and Linder, Peter}, title = {A higher-throughput approach to investigate cardiac contractility in vitro under physiological mechanical conditions}, series = {Journal of Pharmacological and Toxicological Methods}, volume = {105}, journal = {Journal of Pharmacological and Toxicological Methods}, number = {Article 106843}, publisher = {Elsevier}, address = {New York, NY}, doi = {10.1016/j.vascn.2020.106843}, year = {2020}, language = {en} } @article{KnoxBruggemannGossmannetal.2020, author = {Knox, Ronald and Bruggemann, Andrea and Gossmann, Matthias and Thomas, Ulrich and Horv{\´a}th, Andr{\´a}s and Dragicevic, Elena and Stoelzle-Feix, Sonja and Fertig, Niels and Jung, Alexander and Raman, Aravind Hariharan and Staat, Manfred and Linder, Peter}, title = {Combining physiological relevance and throughput for in vitro cardiac contractility measurement}, series = {Biophysical Journal}, volume = {118}, journal = {Biophysical Journal}, number = {Issue 3, Supplement 1}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0006-3495}, doi = {10.1016/j.bpj.2019.11.3104}, pages = {570a}, year = {2020}, abstract = {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.}, language = {en} } @article{LinderBecklerDoerretal.2019, author = {Linder, Peter and Beckler, Matthias and Doerr, Leo and Stoelzle-Feix, Sonja and Fertig, Niels and Jung, Alexander and Staat, Manfred and Gossmann, Matthias}, title = {A new in vitro tool to investigate cardiac contractility under physiological mechanical conditions}, series = {Journal of Pharmacological and Toxicological Methods}, volume = {99}, journal = {Journal of Pharmacological and Toxicological Methods}, number = {Article number 106595}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1056-8719}, doi = {10.1016/j.vascn.2019.05.162}, year = {2019}, language = {en} } @inproceedings{HunkerJungGossmannetal.2019, author = {Hunker, Jan and Jung, Alexander and Goßmann, Matthias and Linder, Peter and Staat, Manfred}, title = {Development of a tool to analyze the conduction speed in microelectrode array measurements of cardiac tissue}, series = {3rd YRA MedTech Symposium 2019 : May 24 / 2019 / FH Aachen}, booktitle = {3rd YRA MedTech Symposium 2019 : May 24 / 2019 / FH Aachen}, editor = {Staat, Manfred and Erni, Daniel}, publisher = {Universit{\"a}t Duisburg-Essen}, address = {Duisburg}, organization = {MedTech Symposium}, isbn = {978-3-940402-22-6}, doi = {10.17185/duepublico/48750}, pages = {7 -- 8}, year = {2019}, abstract = {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.}, language = {en} } @misc{ArtmannLinderBayeretal.2017, author = {Artmann, Gerhard and Linder, Peter and Bayer, Robin and Gossmann, Matthias}, title = {Celldrum electrode arrangement for measuring mechanical stress [Patent of invention]}, publisher = {WIPO}, address = {Geneva}, pages = {18 Seiten}, year = {2017}, abstract = {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.}, language = {en} } @inproceedings{SuryoputriGhaderiLinderetal.2017, author = {Suryoputri, Nathania and Ghaderi, Aydin and Linder, Peter and Kotliar, Konstantin and G{\"o}ttler, Jens and Sorg, Christian and Grimmer, Timo}, title = {Does hemodynamic response function change in Alzheimer disease?}, series = {2nd YRA MedTech Symposium 2017 : June 8th - 9th / 2017 / Hochschule Ruhr-West}, booktitle = {2nd YRA MedTech Symposium 2017 : June 8th - 9th / 2017 / Hochschule Ruhr-West}, editor = {Erni, Daniel and Fischerauer, Alice and Himmel, J{\"o}rg and Seeger, Thomas and Thelen, Klaus}, publisher = {Universit{\"a}t Duisburg-Essen}, address = {Duisburg}, organization = {MedTech Symposium}, isbn = {978-3-9814801-9-1}, doi = {10.17185/duepublico/43984}, pages = {92}, year = {2017}, language = {en} } @article{GossmannFrotscherLinderetal.2016, author = {Goßmann, Matthias and Frotscher, Ralf and Linder, Peter and Bayer, Robin and Epple, U. and Staat, Manfred and Temiz Artmann, Ayseg{\"u}l and Artmann, Gerhard}, title = {Mechano-pharmacological characterization of cardiomyocytes derived from human induced pluripotent stem cells}, series = {Cellular physiology and biochemistry}, volume = {38}, journal = {Cellular physiology and biochemistry}, number = {3}, publisher = {Karger}, address = {Basel}, issn = {1421-9778 (Online)}, doi = {10.1159/000443124}, pages = {1182 -- 1198}, year = {2016}, abstract = {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.}, language = {en} } @article{KowalskiLinderZierkeetal.2016, author = {Kowalski, Julia and Linder, Peter and Zierke, S. and Wulfen, B. van and Clemens, J. and Konstantinidis, K. and Ameres, G. and Hoffmann, R. and Mikucki, J. and Tulaczyk, S. and Funke, O. and Blandfort, D. and Espe, Clemens and Feldmann, Marco and Francke, Gero and Hiecker, S. and Plescher, Engelbert and Sch{\"o}ngarth, Sarah and Dachwald, Bernd and Digel, Ilya and Artmann, Gerhard and Eliseev, D. and Heinen, D. and Scholz, F. and Wiebusch, C. and Macht, S. and Bestmann, U. and Reineking, T. and Zetzsche, C. and Schill, K. and F{\"o}rstner, R. and Niedermeier, H. and Szumski, A. and Eissfeller, B. and Naumann, U. and Helbing, K.}, title = {Navigation technology for exploration of glacier ice with maneuverable melting probes}, series = {Cold Regions Science and Technology}, journal = {Cold Regions Science and Technology}, number = {123}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0165-232X}, doi = {10.1016/j.coldregions.2015.11.006}, pages = {53 -- 70}, year = {2016}, abstract = {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.}, language = {en} } @inproceedings{NiedermeierClemensKowalskietal.2014, author = {Niedermeier, H. and Clemens, J. and Kowalski, Julia and Macht, S. and Heinen, D. and Hoffmann, R. and Linder, Peter}, title = {Navigation system for a research ice probe for antarctic glaciers}, series = {IEEE/ION Position, Location and Navigation Symposium (PLANS) ; 5-8 May 2014, Monterey, Calif.}, booktitle = {IEEE/ION Position, Location and Navigation Symposium (PLANS) ; 5-8 May 2014, Monterey, Calif.}, publisher = {IEEE}, address = {Piscataway, NJ}, organization = {Position, Location and Navigation Symposium <2014, Monterey, Calif.>}, isbn = {978-1-4799-3319-8}, pages = {959 -- 975}, year = {2014}, language = {en} } @article{MiciliValterOflazetal.2013, author = {Micili, Serap C. and Valter, Markus and Oflaz, Hakan and Ozogul, Candan and Linder, Peter and F{\"o}ckler, Nicole and Artmann, Gerhard and Digel, Ilya and Temiz Artmann, Ayseg{\"u}l}, title = {Optical coherence tomography : a potential tool to predict premature rupture of fetal membranes}, series = {Proceedings of the Institution of Mechanical Engineers. Part H : Journal of engineering in medicine}, volume = {Vol. 227}, journal = {Proceedings of the Institution of Mechanical Engineers. Part H : Journal of engineering in medicine}, number = {No. 4}, publisher = {Sage}, address = {London}, issn = {0046-2039 (Print) ; 2041-3033 (E-Journal)}, pages = {393 -- 401}, year = {2013}, language = {en} } @article{DigelDachwaldArtmannetal.2009, author = {Digel, Ilya and Dachwald, Bernd and Artmann, Gerhard and Linder, Peter and Funke, O.}, title = {A concept of a probe for particle analysis and life detection in icy environments}, pages = {1 -- 24}, year = {2009}, language = {en} } @article{KurulganDemirciLinderDemircietal.2009, author = {Kurulgan Demirci, Eylem and Linder, Peter and Demirci, Taylan and Trzewik, J{\"u}rgen and Digel, Ilya and Artmann, Gerhard and Temiz Artmann, Ayseg{\"u}l}, title = {Contractile tension of endothelial cells: An LPS based in-vitro sepsis model}, series = {IUBMB Life. 61 (2009), H. 3}, journal = {IUBMB Life. 61 (2009), H. 3}, publisher = {Wiley}, address = {Weinheim}, isbn = {1521-6543}, pages = {307 -- 308}, year = {2009}, language = {en} } @article{ArtmannDigelLinderetal.2008, author = {Artmann, Gerhard and Digel, Ilya and Linder, Peter and Porst, Dariusz}, title = {Mechanism of haemoglobin sensing body temperature}, series = {Tissue Engineering Part A. 14 (2008), H. 5}, journal = {Tissue Engineering Part A. 14 (2008), H. 5}, isbn = {1937-3341}, pages = {754 -- 754}, year = {2008}, language = {en} } @article{TrzewikTemizArtmannLinderetal.2004, author = {Trzewik, J{\"u}rgen and Temiz Artmann, Ayseg{\"u}l and Linder, Peter and Demirci, T. and Digel, Ilya and Artmann, Gerhard}, title = {Evaluation of lateral mechanical tension in thin-film tissue constructs}, series = {Annals of Biomedical Engineering. 32 (2004), H. 9}, journal = {Annals of Biomedical Engineering. 32 (2004), H. 9}, isbn = {1573-9686}, pages = {1243 -- 1251}, year = {2004}, language = {en} } @article{ZerlinKasischkeDigeletal.2007, author = {Zerlin, Kay and Kasischke, Nicole and Digel, Ilya and Maggakis-Kelemen, Christina and Temiz Artmann, Ayseg{\"u}l and Porst, Dariusz and Kayser, Peter and Linder, Peter and Artmann, Gerhard}, title = {Structural transition temperature of hemoglobins correlates with species' body temperature}, series = {European Biophysics Journal. 37 (2007), H. 1}, journal = {European Biophysics Journal. 37 (2007), H. 1}, isbn = {1432-1017}, pages = {1 -- 10}, year = {2007}, language = {en} } @article{DigelKurulganDemirciLinderetal.2007, author = {Digel, Ilya and Kurulgan Demirci, Eylem and Linder, Peter and Kayser, Peter}, title = {Decrease in extracellular collagen crosslinking after NMR magnetic field application in skin fibroblasts}, series = {Medical and Biological Engineering and Computing. 45 (2007), H. 1}, journal = {Medical and Biological Engineering and Computing. 45 (2007), H. 1}, isbn = {1741-0444}, pages = {91 -- 97}, year = {2007}, language = {en} } @article{DigelMaggakisKelemenZerlinetal.2006, author = {Digel, Ilya and Maggakis-Kelemen, Christina and Zerlin, Kay and Linder, Peter}, title = {Body temperature-related structural transitions of monotremal and human hemoglobin}, series = {Biophysical Journal. 91 (2006), H. 8}, journal = {Biophysical Journal. 91 (2006), H. 8}, isbn = {1542-0086}, pages = {3014 -- 3021}, year = {2006}, language = {en} } @article{KurzLinderTrzewiketal.2010, author = {Kurz, R. and Linder, Peter and Trzewik, J{\"u}rgen and R{\"u}ffer, M. and Artmann, Gerhard and Digel, Ilya and Rothermel, A. and Robitzki, A. and Temiz Artmann, Ayseg{\"u}l}, title = {Contractile tension and beating rates of self-exciting monolayers and 3D-tissue constructs of neonatal rat cardiomyocytes}, series = {Medical and Biological Engineering and Computing}, volume = {48}, journal = {Medical and Biological Engineering and Computing}, number = {1}, publisher = {Springer Nature}, address = {Cham}, issn = {1741-0444}, doi = {10.1007/s11517-009-0552-y}, pages = {59 -- 65}, year = {2010}, abstract = {The CellDrum technology (The term 'CellDrum technology' includes a couple of slightly different technological setups for measuring lateral mechanical tension in various types of cell monolayers or 3D-tissue constructs) was designed to quantify the contraction rate and mechanical tension of self-exciting cardiac myocytes. Cells were grown either within flexible, circular collagen gels or as monolayer on top of respective 1-mum thin silicone membranes. Membrane and cells were bulged outwards by air pressure. This biaxial strain distribution is rather similar the beating, blood-filled heart. The setup allowed presetting the mechanical residual stress level externally by adjusting the centre deflection, thus, mimicking hypertension in vitro. Tension was measured as oscillating differential pressure change between chamber and environment. A 0.5-mm thick collagen-cardiac myocyte tissue construct induced after 2 days of culturing (initial cell density 2 x 10(4) cells/ml), a mechanical tension of 1.62 +/- 0.17 microN/mm(2). Mechanical load is an important growth regulator in the developing heart, and the orientation and alignment of cardiomyocytes is stress sensitive. Therefore, it was necessary to develop the CellDrum technology with its biaxial stress-strain distribution and defined mechanical boundary conditions. Cells were exposed to strain in two directions, radially and circumferentially, which is similar to biaxial loading in real heart tissues. Thus, from a biomechanical point of view, the system is preferable to previous setups based on uniaxial stretching.}, language = {en} }