Effects of electrode diameter on the detection sensitivity and frequency characteristics of electric cell-substrate impedance sensing

Lai, Yi Ting; Chu, Yu‐Xia; Lo, Jeannette; Hung, Yu‐Han; Lo, CM

doi:10.1016/j.snb.2019.02.098

Cited by 22 publications

(22 citation statements)

References 33 publications

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“…Numerical analysis of both micromotion and wound-healing assays successfully distinguished FCCP levels as low as 0.1 μM, lower than the value (1 μM) obtained from our previous investigation using resistance time course measured at 4 kHz [ 10 ]. Capacitance measured at a high frequency (32 kHz or higher) has been suggested as an excellent measure of the cell coverage of the electrode, an indication of the change in cell shape, as well as the damage and recovery of the cell monolayer following injuries [ 13 , 16 ]. Our results confirm the hypothesis that in ECIS high-frequency capacitance measurement provides an exquisitely sensitive assessment of hMSC micromotion and wound-healing migration.…”

Section: Resultsmentioning

confidence: 99%

“…The hill slope was fitted to a sigmoid curve from baseline to the plateau of the reciprocal values of the capacitance time series. The half-time of recovery, T50, was defined as previously described [ 16 , 30 ]. Here, we assume that the recovery rate is inversely proportional to T50.…”

Section: Methodsmentioning

confidence: 99%

“…This is a consequence of the constriction resistance through the medium that is much larger than the faradaic impedance of the working electrode and masks fluctuations caused by the adherent cells. When electrodes are reduced to approximately 10 −3 cm 2 or smaller, the faradaic impedance predominates, and in this situation, the activities of the adherent cells are sensitively revealed [ 16 , 17 ]. For ECIS wound-healing assay, the elevated AC current (~1.5 milliamperes) is applied for up to tens of seconds, resulting in cell killing.…”

Section: Introductionmentioning

confidence: 99%

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Detecting Effects of Low Levels of FCCP on Stem Cell Micromotion and Wound-Healing Migration by Time-Series Capacitance Measurement

Wang¹,

Tung²,

Chiu

et al. 2021

Sensors

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Electric cell–substrate impedance sensing (ECIS) has been used as a real-time impedance-based method to quantify cell behavior in tissue culture. The method is capable of measuring both the resistance and capacitance of a cell-covered microelectrode at various AC frequencies. In this study, we demonstrate the application of high-frequency capacitance measurement (f = 40 or 64 kHz) for the sensitive detection of both the micromotion and wound-healing migration of human mesenchymal stem cells (hMSCs). Impedance measurements of cell-covered electrodes upon the challenge of various concentrations of carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP), from 0.1 to 30 μM, were conducted using ECIS. FCCP is an uncoupler of mitochondrial oxidative phosphorylation (OXPHOS), thereby reducing mitochondrial ATP production. By numerically analyzing the time-series capacitance data, a dose-dependent decrease in hMSC micromotion and wound-healing migration was observed, and the effect was significantly detected at levels as low as 0.1 μM. While most reported works with ECIS use the resistance/impedance time series, our results suggest the potential use of high-frequency capacitance time series for assessing migratory cell behavior such as micromotion and wound-healing migration.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Detecting Effects of Low Levels of FCCP on Stem Cell Micromotion and Wound-Healing Migration by Time-Series Capacitance Measurement

Wang¹,

Tung²,

Chiu

et al. 2021

Sensors

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“…After 24 h of HeLa cell growth on the surface of the microelectrodes, 40 and 80 μg/mL DDP, 40 and 80 μg/mL DOX, and 400 and 800 μg/mL 5-FU were added into culture wells, respectively. The concentrations of DDP, DOX, and 5-FU utilized in the experiment were derived from previous studies [ 25 , 26 , 27 ]. Drug-treated HeLa cells were continuously incubated for 24 h and untreated HeLa cells were taken as the control group.…”

Section: Methodsmentioning

confidence: 99%

The Measurement and Analysis of Impedance Response of HeLa Cells to Distinct Chemotherapy Drugs

Kong

Liu

et al. 2021

Micromachines

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Electric cell–substrate impedance sensing exhibits a real-time and label-free feature to monitor the response of cells stimulated by various biochemical and mechanical signals. Alterations in the currents passing through the cell–electrode system characterize the impedance variations of cells. The impedance responses of HeLa cells under distinct chemotherapy drugs combine the effects of cell proliferation and cell–substrate adhesion. Optimal interdigitated electrodes were selected to explore the impedance responses of HeLa cells. Measurements of impedance of cells in response to three widely used chemotherapy drugs in clinical practice, namely cisplatin, doxorubicin, 5-fluorouracil, were performed. The results demonstrated that distinct impedance responses of HeLa cells to drugs were exhibited and a decrease in measured impedance was observed after drug treatment, accompanied by alterations in the distribution and intensity of the adhesion-related protein vinculin and the rate of cell proliferation. The link between the impedance profiles of HeLa cells and their biological functions was developed based on the circuit model. This study demonstrated the weights of cell proliferation and adhesion of HeLa cells under the treatments of DDP, DOX, and 5-FU, resulted in distinct impedance responses of cells, providing an impedance-based evaluation methodology for cervical cancer treatment.

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“…However, the perforated cell is squeezed in the microchannel rather than its natural state, which may hinder cell recovery 31 . Electric cellsubstrate impedance spectroscopy (ECIS) has been proposed to monitor the status of adherent cells by using microelectrodes on a substrate 32 .…”

Section: Introductionmentioning

confidence: 99%

Single-cell individualized electroporation with real-time impedance monitoring using a microelectrode array chip

2020

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The ability to precisely deliver molecules into single cells while maintaining good cell viability is of great importance to applications in therapeutics, diagnostics, and drug delivery as it is an advancement toward the promise of personalized medicine. This paper reports a single-cell individualized electroporation method with real-time impedance monitoring to improve cell perforation efficiency and cell viability using a microelectrode array chip. The microchip contains a plurality of sextupole-electrode units patterned in an array, which are used to perform in situ electroporation and real-time impedance monitoring on single cells. The dynamic recovery processes of single cells under electroporation are tracked in real time via impedance measurement, which provide detailed transient cell states and facilitate understanding the whole recovery process at the level of single cells. We define single-cell impedance indicators to characterize cell perforation efficiency and cell viability, which are used to optimize electroporation. By applying the proposed electroporation method to different cell lines, including human cancer cell lines and normal human cell lines individually, optimum stimuli are determined for these cells, by which high transfection levels of enhanced green fluorescent protein (EGFP) plasmid into cells are achieved. The results validate the effectiveness of the proposed single-cell individualized electroporation/transfection method and demonstrate promising potential in applications of cell reprogramming, induced pluripotent stem cells, adoptive cell therapy, and intracellular drug delivery technology.

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Effects of electrode diameter on the detection sensitivity and frequency characteristics of electric cell-substrate impedance sensing

Cited by 22 publications

References 33 publications

Detecting Effects of Low Levels of FCCP on Stem Cell Micromotion and Wound-Healing Migration by Time-Series Capacitance Measurement

Detecting Effects of Low Levels of FCCP on Stem Cell Micromotion and Wound-Healing Migration by Time-Series Capacitance Measurement

The Measurement and Analysis of Impedance Response of HeLa Cells to Distinct Chemotherapy Drugs

Single-cell individualized electroporation with real-time impedance monitoring using a microelectrode array chip

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