title: Distinguishing drug-induced minor morphological changes from major cellular damage via label-free impedimetric toxicity screening.
abstract: We present a novel perfusion-based microfluidic platform for label-free drug toxicity screening which can single out non-lethal morphological changes from cellular death using electrical impedance spectroscopy. Minor cellular changes such as cell-cell contacts and major cell injury were identified via impedance phase angle analysis and follow-up of impedance magnitude at different frequencies. Having exposed HepG2/C3A cells to acetaminophen (AP), we showed that continuous drug perfusion caused a time and concentration-dependent impedance decrease. Moreover, perfusion of repeated doses revealed altered dielectric properties of the cell culture after recovery from AP exposure. This study highlights the possibility to sense cellular changes long before cellular death takes place, pointing out the remarkable sensitivity advantage of this technique over standard endpoint viability tests and its interest for toxicology.
authors.affiliation: Laboratoire de Microsystèmes LMIS4, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland. robert.meissner@epfl.ch
authors.forename: Robert
authors.initials: R
authors.lastname: Meissner
authors.forename: Bilge
authors.initials: B
authors.lastname: Eker
authors.forename: Harsha
authors.initials: H
authors.lastname: Kasi
authors.forename: Arnaud
authors.initials: A
authors.lastname: Bertsch
authors.forename: Philippe
authors.initials: P
authors.lastname: Renaud
mesh_terms: D000082:Acetaminophen / Q000633:toxicity*; D048430:Cell Shape / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D017097:Electric Impedance; D004566:Electrodes; D004867:Equipment Design; D005456:Fluorescent Dyes / Q000737:chemistry; D056945:Hep G2 Cells / Q000166:cytology; D006801:Humans; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation / Q000379:methods; D008856:Microscopy, Fluorescence; D018675:Toxicity Tests / Q000379:methods*
chemical_list: D005456:Fluorescent Dyes; D000082:Acetaminophen