title: Time-lapse electrical impedance spectroscopy for monitoring the cell cycle of single immobilized S. pombe cells.
abstract: As a complement and alternative to optical methods, wide-band electrical impedance spectroscopy (EIS) enables multi-parameter, label-free and real-time detection of cellular and subcellular features. We report on a microfluidics-based system designed to reliably capture single rod-shaped Schizosaccharomyces pombe cells by applying suction through orifices in a channel wall. The system enables subsequent culturing of immobilized cells in an upright position, while dynamic changes in cell-cycle state and morphology were continuously monitored through EIS over a broad frequency range. Besides measuring cell growth, clear impedance signals for nuclear division have been obtained. The EIS system has been characterized with respect to sensitivity and detection limits. The spatial resolution in measuring cell length was 0.25 μm, which corresponds to approximately a 5-min interval of cell growth under standard conditions. The comprehensive impedance data sets were also used to determine the occurrence of nuclear division and cytokinesis. The obtained results have been validated through concurrent confocal imaging and plausibilized through comparison with finite-element modeling data. The possibility to monitor cellular and intracellular features of single S. pombe cells during the cell cycle at high spatiotemporal resolution renders the presented microfluidics-based EIS system a suitable tool for dynamic single-cell investigations.
authors.affiliation: ETH Zurich, Department of Biosystems Science and Engineering, Bio Engineering Laboratory, Mattenstrasse 26, CH-4058 Basel, Switzerland.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: ETH Zurich, Department of Biosystems Science and Engineering, Bio Engineering Laboratory, Mattenstrasse 26, CH-4058 Basel, Switzerland.
authors.forename: Olivier
authors.initials: O
authors.lastname: Frey
authors.affiliation: ETH Zurich, Department of Biosystems Science and Engineering, Bio Engineering Laboratory, Mattenstrasse 26, CH-4058 Basel, Switzerland.
authors.forename: Niels
authors.initials: N
authors.lastname: Haandbaek
authors.affiliation: ETH Zurich, Department of Biosystems Science and Engineering, Bio Engineering Laboratory, Mattenstrasse 26, CH-4058 Basel, Switzerland.
authors.forename: Felix
authors.initials: F
authors.lastname: Franke
authors.affiliation: ETH Zurich, Department of Biosystems Science and Engineering, Computational Systems Biology Group, Mattenstrasse 26, CH-4058 Basel, Switzerland.
authors.forename: Fabian
authors.initials: F
authors.lastname: Rudolf
authors.affiliation: ETH Zurich, Department of Biosystems Science and Engineering, Bio Engineering Laboratory, Mattenstrasse 26, CH-4058 Basel, Switzerland.
authors.forename: Andreas
authors.initials: A
authors.lastname: Hierlemann
mesh_terms: D002453:Cell Cycle; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D018914:Cells, Immobilized / Q000166:cytology; D003198:Computer Simulation; D048749:Cytokinesis; D058266:Dielectric Spectroscopy / Q000379:methods*; D020342:Finite Element Analysis; D044085:Microfluidics; D012568:Schizosaccharomyces / Q000166:cytology* / Q000254:growth & development; D059008:Time-Lapse Imaging / Q000379:methods*