PMID- 38266619 OWN - NLM STAT- MEDLINE DCOM- 20240214 LR - 20240214 IS - 1873-4235 (Electronic) IS - 0956-5663 (Linking) VI - 250 DP - 2024 Apr 15 TI - Microcavity well-plate for automated parallel bioelectronic analysis of 3D cell cultures. PG - 116042 LID - S0956-5663(24)00045-9 [pii] LID - 10.1016/j.bios.2024.116042 [doi] AB - Three-dimensional (3D) in vitro cell culture models serve as valuable tools for accurately replicating cellular microenvironments found in vivo. While cell culture technologies are rapidly advancing, the availability of non-invasive, real-time, and label-free analysis methods for 3D cultures remains limited. To meet the demand for higher-throughput drug screening, there is a demanding need for analytical methods that can operate in parallel. Microelectrode systems in combination with microcavity arrays (MCAs), offer the capability of spatially resolved electrochemical impedance analysis and field potential monitoring of 3D cultures. However, the fabrication and handling of small-scale MCAs have been labour-intensive, limiting their broader application. To overcome this challenge, we have established a process for creating MCAs in a standard 96-well plate format using high-precision selective laser etching. In addition, to automate and ensure the accurate placement of 3D cultures on the MCA, we have designed and characterized a plug-in tool using SLA-3D-printing. To characterize our new 96-well plate MCA-based platform, we conducted parallel analyses of human melanoma 3D cultures and monitored the effect of cisplatin in real-time by impedance spectroscopy. In the following we demonstrate the capabilities of the MCA approach by analysing contraction rates of human pluripotent stem cell-derived cardiomyocyte aggregates in response to cardioactive compounds. In summary, our MCA system significantly expands the possibilities for label-free analysis of 3D cell and tissue cultures, offering an order of magnitude higher parallelization capacity than previous devices. This advancement greatly enhances its applicability in real-world settings, such as drug development or clinical diagnostics. CI - Copyright (c) 2024 The Authors. Published by Elsevier B.V. All rights reserved. FAU - Zitzmann, Franziska D AU - Zitzmann FD AD - Centre for Biotechnology and Biomedicine, Biochemical Cell Technology, Leipzig University, Deutscher Platz 5, D-04103, Leipzig, Germany; b-ACT Matter, Research and Transfer Centre for bioactive Matter, Leipzig University, Deutscher Platz 5, D-04103, Leipzig, Germany. FAU - Schmidt, Sabine AU - Schmidt S AD - Centre for Biotechnology and Biomedicine, Biochemical Cell Technology, Leipzig University, Deutscher Platz 5, D-04103, Leipzig, Germany. FAU - Frank, Ronny AU - Frank R AD - Centre for Biotechnology and Biomedicine, Biochemical Cell Technology, Leipzig University, Deutscher Platz 5, D-04103, Leipzig, Germany. FAU - Weigel, Winnie AU - Weigel W AD - Centre for Biotechnology and Biomedicine, Biochemical Cell Technology, Leipzig University, Deutscher Platz 5, D-04103, Leipzig, Germany. FAU - Meier, Matthias AU - Meier M AD - Centre for Biotechnology and Biomedicine, Biochemical Cell Technology, Leipzig University, Deutscher Platz 5, D-04103, Leipzig, Germany; Helmholtz Pioneer Campus, Helmholtz Zentrum Munich, Neuherberg, Germany. FAU - Jahnke, Heinz-Georg AU - Jahnke HG AD - Centre for Biotechnology and Biomedicine, Biochemical Cell Technology, Leipzig University, Deutscher Platz 5, D-04103, Leipzig, Germany. Electronic address: heinz-georg.jahnke@bbz.uni-leipzig.de. LA - eng PT - Journal Article DEP - 20240114 PL - England TA - Biosens Bioelectron JT - Biosensors & bioelectronics JID - 9001289 SB - IM MH - Humans MH - *Biosensing Techniques MH - Myocytes, Cardiac MH - Cell Culture Techniques/methods MH - Cell Culture Techniques, Three Dimensional MH - Dielectric Spectroscopy OTO - NOTNLM OT - 3D cell culture OT - Contractile human cardiomyocyte clusters OT - Electrochemical impedance spectroscopy OT - Field potential monitoring OT - Microcavity array technology OT - Selective laser etching COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2024/01/25 00:42 MHDA- 2024/02/12 05:43 CRDT- 2024/01/24 18:35 PHST- 2023/10/31 00:00 [received] PHST- 2024/01/10 00:00 [revised] PHST- 2024/01/12 00:00 [accepted] PHST- 2024/02/12 05:43 [medline] PHST- 2024/01/25 00:42 [pubmed] PHST- 2024/01/24 18:35 [entrez] AID - S0956-5663(24)00045-9 [pii] AID - 10.1016/j.bios.2024.116042 [doi] PST - ppublish SO - Biosens Bioelectron. 2024 Apr 15;250:116042. doi: 10.1016/j.bios.2024.116042. Epub 2024 Jan 14.