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.

Impedimetric Toxicity Assay in Microfluidics Using Free and Liposome-Encapsulated Anticancer Drugs

“…Introduction of 500 μM OX results in a corresponding increase in Cell Index; however, due to the increased cytotoxic effect, the observed Cell Index increase has a significantly shorter duration and lower magnitude (Supporting Information Figure S2). This behavior, previously observed in EIS-based assays using other drugs or cell lines, has been attributed to drug-induced stress, which cells try to overcome by increasing their metabolism 30,42,49 or changing their morphology and adhesion. 49 When comparing these data with results obtained in MTS assays performed at different time points with the same cell density and drug concentration, a weak increase in cellular metabolism can be observed upon introduction of OX (Supporting Information Figure S3).…”

Electrical impedance sensor for quantitative monitoring of infection processes on HCT-8 cells by the waterborne parasite Cryptosporidium

“…The circuit, schematized in Fig. 2A and B, was inspired by a previously used lumped circuit (Meissner et al, 2011). The ionic double layer is modeled by a constant-phase element (CPE, see Eq.…”

“…The combined use of IS and microelectrodes has demonstrated its usefulness in the field of cell biology. Pionneered by Giaever and Keese (1984) and adapted to Interdigitated Microelectrode Arrays (IMA) by Ehret et al (1997), it has emerged as a powerful tool and been used to study a wide range of cellular phenomena such as cell adhesion and proliferation (Atienza et al, 2005;Wang et al, 2008;Wegener et al, 2000), cell confluency (De Blasio et al, 2004), cell apoptosis after chemical treatments (Arndt et al, 2004;Meissner et al, 2011;Solly et al, 2004) or stem cell differentiation (Bagnaninchi and Drummond, 2011). However, this technique has never been used either to get continuous information on the host cell response during protozoan parasite infection or to assess their infectivity.…”

Chip-based liver equivalents for toxicity testing – organotypicalness versus cost-efficient high throughput

“…The obvious difficulty in determining cell damage exactly in such small sieve-pockets of 250 cells has been addressed by Meissner and colleagues. 69 They provided a solution for an integrated label-free impedimetric toxicity screening capable of detecting cellular damage in microscale sieve-pockets.…”