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Schmidt, S.* ; Li, W.* ; Schubert, M.* ; Binnewerg, B.* ; Prönnecke, C.* ; Zitzmann, F.D.* ; Bulst, M.* ; Wegner, S.* ; Meier, M. ; Guan, K.* ; Jahnke, H.G.*

Novel high-dense microelectrode array based multimodal bioelectronic monitoring system for cardiac arrhythmia re-entry analysis.

Biosens. Bioelectron. 252:116120 (2024)

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	Open Access Gold (Paid Option)

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In recent decades, significant progress has been made in the treatment of heart diseases, particularly in the field of personalized medicine. Despite the development of genetic tests, phenotyping and risk stratification are performed based on clinical findings and invasive in vivo techniques, such as stimulation conduction mapping techniques and programmed ventricular pacing. Consequently, label-free non-invasive in vitro functional analysis systems are urgently needed for more accurate and effective in vitro risk stratification, model-based therapy planning, and clinical safety profile evaluation of drugs. To overcome these limitations, a novel multilayer high-density microelectrode array (HD-MEA), with an optimized configuration of 512 sensing and 4 pacing electrodes on a sensor area of 100 mm², was developed for the bioelectronic detection of re-entry arrhythmia patterns. Together with a co-developed front-end, we monitored label-free and in parallel cardiac electrophysiology based on field potential monitoring and mechanical contraction using impedance spectroscopy at the same microelectrode. In proof of principle experiments, human induced pluripotent stem cell (hiPS)-derived cardiomyocytes were cultured on HD-MEAs and used to demonstrate the sensitive quantification of contraction strength modulation by cardioactive drugs such as blebbistatin (IC₅₀ = 4.2 μM), omecamtiv and levosimendan. Strikingly, arrhythmia-typical rotor patterns (re-entry) can be induced by optimized electrical stimulation sequences and detected with high spatial resolution. Therefore, we provide a novel cardiac re-entry analysis system as a promising reference point for diagnostic approaches based on in vitro assays using patient-specific hiPS-derived cardiomyocytes.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Electrical Stimulator-based Pacing ; Field Potential Monitoring ; Impedimetric Contraction Strength Monitoring ; Large-area Microelectrode Array ; Rotor Pattern Detection; Cardiomyocytes; Blebbistatin; Levosimendan; Tissue; Cells

ISSN (print) / ISBN 0956-5663

e-ISSN 1873-4235

Journal Biosensors and Bioelectronics

Quellenangaben Volume: 252, Article Number: 116120

Publisher Elsevier

Publishing Place Oxford Fulfillment Centre The Boulevard, Langford Lane, Kidlington, Oxford Ox5 1gb, Oxon, England

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Helmholtz Pioneer Campus (HPC)

Grants European Union (EFRE)
Saxon Ministry of Science and the Fine Arts (SMWK)