title: Automated, Multiplexed Electrical Impedance Spectroscopy Platform for Continuous Monitoring of Microtissue Spheroids.
abstract: Microtissue spheroids in microfluidic devices are increasingly used to establish novel in vitro organ models of the human body. As the spheroids are comparably sizable, it is difficult to monitor larger numbers of them by optical means. Therefore, electrical impedance spectroscopy (EIS) emerges as a viable alternative to probing spheroid properties. Current spheroid EIS systems are, however, not suitable for investigating multiple spheroids in parallel over extended time in an automated fashion. Here we address this issue by presenting an automated, multiplexed EIS (AMEIS) platform for impedance analysis in a microfluidic setting. The system was used to continuously monitor the effect of the anticancer drug fluorouracil (5-FU) on HCT116 cancer spheroids. Simultaneous EIS monitoring of up to 15 spheroids was performed in parallel over 4 days at a temporal resolution of 2 min without any need for pumps. The measurements were continuous in nature, and the setup was kept in a standard incubator under controlled conditions during the measurements. A baseline normalization method to improve robustness and to reduce the influence of slow changes in the medium conductivity on the spheroid EIS readings has been developed and validated by experiments and means of a finite-element model. The same method and platform was then used for online monitoring of cardiac spheroids. The beating frequency of each cardiac spheroid could be read out in a completely automated fashion. The developed system constitutes a promising method for simultaneously evaluating drug impact and/or toxic effects on multiple microtissue spheroids.
authors.affiliation: Department of Biosystems Science and Engineering, ETH Zurich , Mattenstrasse 26, Basel 4058, Switzerland.
authors.forename: Sebastian C
authors.initials: SC
authors.lastname: Bürgel
authors.affiliation: Department of Biosystems Science and Engineering, ETH Zurich , Mattenstrasse 26, Basel 4058, Switzerland.
authors.forename: Laurin
authors.initials: L
authors.lastname: Diener
authors.affiliation: Department of Biosystems Science and Engineering, ETH Zurich , Mattenstrasse 26, Basel 4058, Switzerland.
authors.forename: Olivier
authors.initials: O
authors.lastname: Frey
authors.affiliation: Department of Biosystems Science and Engineering, ETH Zurich , Mattenstrasse 26, Basel 4058, Switzerland.
authors.forename: Jin-Young
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Department of Biosystems Science and Engineering, ETH Zurich , Mattenstrasse 26, Basel 4058, Switzerland.
authors.forename: Andreas
authors.initials: A
authors.lastname: Hierlemann
mesh_terms: D001331:Automation; D058266:Dielectric Spectroscopy / Q000295:instrumentation*; D017097:Electric Impedance; D045325:HCT116 Cells; D006801:Humans; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation; D010316:Particle Size; D018874:Spheroids, Cellular / Q000737:chemistry*; D013499:Surface Properties