Microcavity array (MCA)-based biosensor chip for functional drug screening of 3D tissue models
Abstract
Multicellular tumour spheroids that mimic a native cellular environment are widely used as model systems for drug testing. To study drug effects on three-dimensional cultures in real-time we designed and fabricated a novel type of sensor chip for fast, non-destructive impedance spectroscopy and extracellular recording. Precultured spheroids are trapped between four gold electrodes. Fifteen individual 100microm deep square microcavities with sizes from 200 to 400microm allow an optimised positioning during the measurement. Although apoptosis was induced in human melanoma spheroids by Camptothecin (CTT), treated cultures did not show disintegration but displayed increased impedance magnitudes compared to controls after 8h resulting from an altered morphology of the outer cells. Contractions in cardiomyocyte spheroids were monitored when the innovative chip was used for recording of extracellular potentials. The silicon-based electrode array is used as an acute test system for the monitoring of any kind of 3D cell cultures. Since no adherence of cells or labelling is necessary the multifunctional sensor chip provides a basis for improved drug development by high content screenings with reduced costs and assay times. Additional improvements for parallel testing of different substances on one chip are presented.
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In microcavity and microcapillary designs, it is important that the size of the cavity or capillary match the size of spheroids, allowing the spheroids to be adequately analyzed by maintaining their shape and properties during measurements.
“In both the microcavity and the microcapillary designs, it is important that the size of the cavity or capillary match with the size of spheroids, allowing the spheroids to be adequately analyzed by maintaining their shape and properties during measurements. 88”
From Three-dimensional cell culture systems and their applications in drug discovery and cell-based biosensors (2014) · cites this paper as [88]
Kloss et al. demonstrated that drug-induced apoptosis in spheroids displayed increased impedance magnitudes, resulting from an altered morphology of the outer cells, using the microcavity system.
“Kloss et al . demonstrated that drug-induced apoptosis in spheroids displayed increased impedance magnitudes, resulting from an altered morphology of the outer cells, using the microcavity system. 88”
From Three-dimensional cell culture systems and their applications in drug discovery and cell-based biosensors (2014) · cites this paper as [88]
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- Authors
- Kloß, D., Kurz, R., Jahnke, H.-G., Fischer, M., Rothermel, A., Anderegg, U., Simon, J. C., & Robitzki, A. A.
- Affiliations
- Leipzig University (DE)
- Technische Universität Ilmenau (DE)
- University Hospital Leipzig (DE)
- Corresponding author
- Robitzki, Andrea A.
- ORCID
- Venue
- Biosensors and Bioelectronics
- Publisher
- Elsevier BV
- Published
- 2008-05
- Volume
- 23
- Issue
- 10
- Pages
- 1473-1480
- ISSN
- 0956-5663 (ISSN-L)
- OpenAlex
- W2000315568
- Cited by
- 77
- References
- 18
- Citations by year
- 2025: 1 · 2024: 3 · 2023: 1 · 2022: 3 · 2021: 4 · 2020: 11 · 2019: 7 · 2018: 4 · 2017: 5 · 2016: 3 · 2015: 1 · 2014: 7 · 2013: 5 · 2012: 7
- FWCI
- 2.15
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biosensors and Bioelectronics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neural Engineering
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Physical Sciences › Engineering › Biomedical Engineering › Microfluidic and Bio-sensing Technologies
- Keywords
- microcavity arrays, sensor chip, impedance spectroscopy, tumor spheroids, 3D cell culture, drug screening, high-content screening, apoptosis, camptothecin, cardiomyocyte contraction, gold electrode, real-time monitoring
- MeSH terms
- Biological Assay, Drug Evaluation, Preclinical, Equipment Design, Spectrum Analysis, Biosensing Techniques, Electric Impedance, Neoplasms, Bone Tissue, Cell Culture Techniques, Equipment Failure Analysis, Microfluidic Analytical Techniques, Tissue Array Analysis
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