COMSOL modeling of an integrated impedance sensor in a hanging-drop platform
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1
ETH Zürich, Department of Biosystems Science and Engineering, Switzerland
Motivation
Traditional dish-based, two-dimensional cell cultures have limited prediction capability for drug testing, whereas three-dimensional spherical microtissues (spheroids) and organoids much more accurately replicate physiological conditions of cells in the respective tissue [1,2]. Such spheroids can be formed and cultured in microphysiological multi-tissue formats by using the hanging-drop technology as depicted in Fig. 1 [3]. Like most other microfluidic platforms, the hanging-drop platform still requires a microscope for visual inspection and considerable time for doing off-line measurements, as the spheroids/media have to be harvested from the microfluidic device for labeling and chemical analysis. It would be beneficial to have an integrated on-line multi-functional sensor as an additional readout, located directly at the tissue sites in the hanging-drop platform, so that measurements can be performed in situ and without harvesting medium or the tissue and without interrupting the overall culturing process.
Material and Methods
The proposed sensor chip includes a configurable microelectrode array (2 mm x 2 mm) with integrated impedance spectroscopy readout on a single CMOS chip, that will be used for microtissue growth profiling. A model has been developed and simulated by COMSOL Multiphysics to investigate the effect of physical parameters, such as hanging-drop dimensions, to find an optimal electrode size. Fig. 2 (a) shows the implemented model, which includes a droplet (filled by medium), a microtissue, reference electrode, and an example working electrode. The medium (electrolyte) was modeled with a conductivity of 1.2 S/m, and the microtissue as an insulator with a conductivity of 0.01 S/m. The electrode-electrolyte interface was modeled by a double-layer capacitance of 0.25 F/m2 [4].
Results
Fig. 2 (b) shows the current density in the medium while applying a sinusoidal voltage to the reference electrode and measuring the current through the working electrode. Fig. 2 (c) illustrates the effect of the spheroid size on the measured impedance for three electrode sizes, which shows that larger electrodes provide better-quality data for monitoring spheroid growth.
Summary and conclusion
A COMSOL model of a hanging-drop platform was developed, and the effects of electrodes and hanging-droplet dimensions were investigated. Results showed that in order to monitor the microtissue growth through impedance measurements, working electrodes should be larger than 100 µm × 100 µm.
Acknowledgements
Acknowledgements
Financial support through MHV Grant 171267 and ERC Advanced Grant 694829 “neuroXscales” are acknowledged.
References
[1] Clevers, H., et al, Modeling Development and Disease with Organoids. Cell press, 2016.
[2] Tung, Y.C., et al, High-throughput 3D spheroid culture and drug testing using a 384 hanging drop array. Analyst, 2011.
[3] Frey, O., et al, Reconfigurable microfluidic hanging drop network for multi-tissue interaction and analysis. Nature Communications, 2014.
[4] Franks, W., et al, Impedance characterization and modeling of electrodes for biomedical applications, IEEE Trans. Biomed. Eng., 2005.
Keywords:
Impedance sensor,
Hanging drop,
Microtissue,
microfluidic system,
electrode array
Conference:
MEA Meeting 2018 | 11th International Meeting on Substrate Integrated Microelectrode Arrays, Reutlingen, Germany, 4 Jul - 6 Jul, 2018.
Presentation Type:
Poster Presentation
Topic:
Microphysiological systems
Citation:
Bounik
R,
Gusmaroli
M,
Viswam
V,
Modena
MM and
Hierlemann
A
(2019). COMSOL modeling of an integrated impedance sensor in a hanging-drop platform.
Conference Abstract:
MEA Meeting 2018 | 11th International Meeting on Substrate Integrated Microelectrode Arrays.
doi: 10.3389/conf.fncel.2018.38.00083
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Received:
18 Mar 2018;
Published Online:
17 Jan 2019.
*
Correspondence:
Ms. Raziyeh Bounik, ETH Zürich, Department of Biosystems Science and Engineering, Zurich, Switzerland, raziyeh.bounik@bsse.ethz.ch