A cell impedance measurement device for the cytotoxicity assay dependent on the velocity of supplied toxic fluid

Abstract

We present a cell impedance measurement chip capable of characterizing the toxic response of cells depending on the velocity of the supplied toxic fluid. Previous impedance-based devices using a single open-top chamber have been limited to maintaining a constant supply velocity, and devices with a single closed-top chamber present difficulties in simultaneous cytotoxicity assay for varying levels of supply velocities. The present device, capable of generating constant and multiple levels of toxic fluid velocity simultaneously within a single stepwise microchannel, performs a cytotoxicity assay dependent on toxic fluid velocity, in order to find the effective velocity of toxic fluid to cells for maximizing the cytotoxic effect. We analyze the cellular toxic response of 5% ethanol media supplied to cancer cells within a toxic fluid velocity range of 0–8.3 mm s−1. We observe the velocity-dependent cell detachment rate, impedance, and death rate. We find that the cell detachment rate decreased suddenly to 2.4% at a velocity of 4.4 mm s−1, and that the change rates of cell resistance and cell capacitance showed steep decreases to 8% and 41%, respectively, at a velocity of 5.7 mm s−1. The cell death rate and impedance fell steeply to 32% at a velocity of 5.7 mm s−1. We conclude that: (1) the present device is useful in deciding on the toxic fluid velocity effective to cytotoxicity assay, since the cellular toxic response is dependent on the velocity of toxic fluid, and; (2) the cell impedance analysis facilitates a finer cellular response analysis, showing better correlation with the cell death rate, compared to conventional visual observation. The present device, capable of performing the combinational analysis of toxic fluid velocity and cell impedance, has potential for application to the fine cellular toxicity assay of drugs with proper toxic fluid velocity.

Real-time physiological sensor-based liver-on-chip device for monitoring drug toxicity

“…Keeping track of this factor allows for the detection of drug-induced metabolic anomalies, which can reveal the drug's pharmacokinetics on the cellular or organism level. Hence, there is a dire need for real-time monitoring of the physiological condition of the organ-on-chip models [5][6][7][8][9]. Understanding the peculiar mechanism of toxicity of a drug or chemical provides the possibility of forecasting its toxic effect in relevant organs through in vitro assay and in silico modelling, ultimately reducing the role of animal testing.…”

In-Line Analysis of Organ-on-Chip Systems with Sensors: Integration, Fabrication, Challenges, and Potential

“…They designed a microfluidic system with a stepwise increasing flow speed obtained through a narrowing of the channel width. 64 Cells were cultured in the whole microchannel and ECIS sensors fabricated from ITO were placed in each flow speed area. This allowed for evaluation of the cytotoxicity of the flushed medium at different flow speeds simultaneously by measuring changes in cell adhesion at different locations along the channel.…”

“…Kang et al made use of this in their flow-speed-dependent cytotoxicity assay chip. They designed a microfluidic system with a stepwise increasing flow speed obtained through a narrowing of the channel width . Cells were cultured in the whole microchannel and ECIS sensors fabricated from ITO were placed in each flow speed area.…”

“…14 Optical access could be an issue when electrodes are placed above or below cells as transmission microscopy is often essential for cell characterization. To circumvent this, transparent electrode materials, such as indium tin oxide (ITO) 64 may be used. Another approach is to observe cells next to or in-between the microstructured electrodes.…”

High performance inkjet printed embedded electrochemical sensors for monitoring hypoxia in a gut bilayer microfluidic chip

“…27 This creates significant ground for a systematic study of gut-on-a-chip devices in the context of DO changes associated with HIF-1α and monitoring the production of ROS in the endothelium. While trans-epithelial electrical impedance (TEEI) is a proven technique used for monolayer barrier assessment in real time [34][35][36][37][38][39][40][41][42][43][44][45] and can also be utilized for combined bilayer barrier impedance measurement. Inkjet printing has been used to pattern microelectrodes 46 for electrochemical measurements of dissolved oxygen in organ chips.…”