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Zitzmann, F.D.* ; Schmidt, S.* ; Frank, R.* ; Weigel, W.* ; Meier, M. ; Jahnke, H.G.*

Microcavity well-plate for automated parallel bioelectronic analysis of 3D cell cultures.

Biosens. Bioelectron. 250:116042 (2024)
DOI PMC
Creative Commons Lizenzvertrag
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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords 3d Cell Culture ; Contractile Human Cardiomyocyte Clusters ; Electrochemical Impedance Spectroscopy ; Field Potential Monitoring ; Microcavity Array Technology ; Selective Laser Etching; Microelectrode Array; Cardiomyocytes; Blebbistatin; Tissue; Chip; 2d
ISSN (print) / ISBN 0956-5663
e-ISSN 1873-4235
Journal Biosensors and Bioelectronics
Quellenangaben Volume: 250, Issue: , Pages: , Article Number: 116042 Supplement: ,
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 Saxon Ministry of Science and the Fine Arts (SMWK)
European Union (EFRE)
Federal Ministry for Economics Affairs and Climate Action of Germany (BMWK)
Federal Ministry of Education and Research of Germany (BMBF)