@inproceedings{RamanJungHorvathetal.2019,
  author    = {Raman, Aravind Hariharan and Jung, Alexander and Horv{\´a}th, Andr{\´a}s and Becker, Nadine and Staat, Manfred},
  title     = {Modification of a computer model of human stem cell-derived cardiomyocyte electrophysiology based on Patch-Clamp measurements},
  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     = {10 -- 11},
  year      = {2019},
  abstract  = {Human induced pluripotent stem cells (hiPSCs) have shown to be promising in disease studies and drug screenings [1]. Cardiomyocytes derived from hiPSCs have been extensively investigated using patch-clamping and optical methods to compare their electromechanical behaviour relative to fully matured adult cells. Mathematical models can be used for translating findings on hiPSCCMs to adult cells [2] or to better understand the mechanisms of various ion channels when a drug is applied [3,4]. Paci et al. (2013) [3] developed the first model of hiPSC-CMs, which they later refined based on new data [3]. The model is based on iCells® (Fujifilm Cellular Dynamics, Inc. (FCDI), Madison WI, USA) but major differences among several cell lines and even within a single cell line have been found and motivate an approach for creating sample-specific models. We have developed an optimisation algorithm that parameterises the conductances (in S/F=Siemens/Farad) of the latest Paci et al. model (2018) [5] using current-voltage data obtained in individual patch-clamp experiments derived from an automated patch clamp system (Patchliner, Nanion Technologies GmbH, Munich).},
  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{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}
}
@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}
}