A cell-microelectronic sensing technique for profiling cytotoxicity of chemicals

Boyd, Jessica M.; Huang, Li; Xie, Li; Moe, Birget; Gabos, Stephan; Li, Xing‐Fang

doi:10.1016/j.aca.2008.03.047

Cited by 81 publications

(39 citation statements)

References 34 publications

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“…The relative electrical changes during a measurement are displayed by xCELLigence software as a unitless parameter termed Cell Index, which is calculated as a relative change in actual impedance divided by a previously registered background value. Thus, real-time measurement of cell index can give information on the actual cell viability status, and has been used in a number of cell morphology, adhesion, cell proliferation and receptor activity studies (11,(25)(26)(27).…”

Section: Discussionmentioning

confidence: 99%

“…One of the most sophisticated new techniques is the real-time cell electronic sensing technology, based on a special microelectronic sensor-based platform. This real-time electronic sensing system (RT-CES) provides a label-free detection of cell viability status in a simple homogeneous assay format, noninvasive measurement, reduced interference with normal cell function, kinetic measurement, and reduced time for assay development (10,11). Here we apply this method to enable the screening for cytoprotective compounds in realtime.…”

Section: Introductionmentioning

confidence: 99%

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A cell-microelectronic sensing technique for the screening of cytoprotective compounds

Ózsvári¹,

Puskás

Nagy³

et al. 2010

Int J Mol Med

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Abstract. In recent years, a new cell-based high throughput paradigm has emerged, which seeks to identify novel, pharmacologically active cytoprotective compounds. The essence of this approach is to create experimental models of cell injury relevant for a particular disease by establishing in vitro cellbased models, followed by high-throughput testing of compounds that affect the cellular response in a desired manner. Prior approaches typically used simple end-point analyses. To assess the cytoprotective effects of novel drug candidates in real-time, we have applied a cell-microelectronic sensing technique (RT-CES), which measures changes in the impedance of individual microelectronic wells that correlates linearly with cell index (reflecting cell number, adherence and cell growth), thereby allowing the continuous determination of cell viability during oxidative stress. In vitro cytotoxicity was elicited by hydrogen peroxide in myocytes (H9c2) and hepatocytes (Hep3B). Cells were post-treated at 30 min with various reference molecules and novel cytoprotective compounds. Cytoprotection detected in the RT-CES system correlated well with the results of two classical end-pointbased methods (improvement in MTT and reduction of LDH release). The RT-CES method, when used as described in the current report, is suitable for the screening of molecular libraries to identify molecules or molecule combinations that attenuate oxidative stress-induced cell damage.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A cell-microelectronic sensing technique for the screening of cytoprotective compounds

Ózsvári¹,

Puskás

Nagy³

et al. 2010

Int J Mol Med

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“…The more the cells attach to the electrodes, the higher the electronic impedence which is read as cell index (CI). This assay has been described for the measurement of cytotoxicity [32][33][34] and can be used to determine other cellular parameters such as cell proliferation, cytotoxicity start time, cell recovery and cell response patterns [34] represented by CI changes which could either be proliferating (increasing CI), cytotoxic (decreasing CI) or cytostatic (stable CI).…”

Section: Effect Of the Complexes On Viral Infectivity Viability And mentioning

confidence: 99%

New bis(thiosemicarbazonate) gold(III) complexes inhibit HIV replication at cytostatic concentrations: Potential for incorporation into virostatic cocktails

Fonteh

Keter

Meyer

2011

Journal of Inorganic Biochemistry

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“…The xCELLigence instrument, manufactured by Roche, utilizes a similar technique to measure changes in electrical impedance as cells attach and spread in a culture dish covered with a gold microelectrode array that covers approximately 80% of the area on the bottom of a well. As cells attach and spread on the electrode surface, it leads to an increase in electrical impedance [9][10][11][12] . The impedance is displayed as a dimensionless parameter termed cell-index, which is directly proportional to the total area of tissue-culture well that is covered by cells.…”

Section: Introductionmentioning

confidence: 99%

A Real-time Electrical Impedance Based Technique to Measure Invasion of Endothelial Cell Monolayer by Cancer Cells

Rahim

Üren

2011

JoVE

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Metastatic dissemination of malignant cells requires degradation of basement membrane, attachment of tumor cells to vascular endothelium, retraction of endothelial junctions and finally invasion and migration of tumor cells through the endothelial layer to enter the bloodstream as a means of transport to distant sites in the host [1][2][3] . Once in the circulatory system, cancer cells adhere to capillary walls and extravasate to the surrounding tissue to form metastatic tumors 4,5 . The various components of tumor cell-endothelial cell interaction can be replicated in vitro by challenging a monolayer of human umbilical vein endothelial cells (HUVEC) with cancer cells. Studies performed with electron and phasecontrast microscopy suggest that the in vitro sequence of events fairly represent the in vivo metastatic process 6 . Here, we describe an electricalimpedance based technique that monitors and quantifies in real-time the invasion of endothelial cells by malignant tumor cells. Giaever and Keese first described a technique for measuring fluctuations in impedance when a population of cells grow on the surface of electrodes 7,8 . The xCELLigence instrument, manufactured by Roche, utilizes a similar technique to measure changes in electrical impedance as cells attach and spread in a culture dish covered with a gold microelectrode array that covers approximately 80% of the area on the bottom of a well. As cells attach and spread on the electrode surface, it leads to an increase in electrical impedance [9][10][11][12] . The impedance is displayed as a dimensionless parameter termed cell-index, which is directly proportional to the total area of tissue-culture well that is covered by cells. Hence, the cell-index can be used to monitor cell adhesion, spreading, morphology and cell density.The invasion assay described in this article is based on changes in electrical impedance at the electrode/cell interphase, as a population of malignant cells invade through a HUVEC monolayer (Figure 1). The disruption of endothelial junctions, retraction of endothelial monolayer and replacement by tumor cells lead to large changes in impedance. These changes directly correlate with the invasive capacity of tumor cells, i.e., invasion by highly aggressive cells lead to large changes in cell impedance and vice versa. This technique provides a two-fold advantage over existing methods of measuring invasion, such as boyden chamber and matrigel assays: 1) the endothelial cell-tumor cell interaction more closely mimics the in vivo process, and 2) the data is obtained in real-time and is more easily quantifiable, as opposed to end-point analysis for other methods. Video LinkThe video component of this article can be found at https://www.jove.com/video/2792/ Protocol 1. Preparation 1. All steps should be performed under sterile conditions in a tissue culture hood. 2. The xCELLigence station is placed in a 37°C incubator in the presence of 5% CO 2 . 3. Use low passage HUVEC cells, preferably no more than passage 6. Also, make sure tha...

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A cell-microelectronic sensing technique for profiling cytotoxicity of chemicals

Cited by 81 publications

References 34 publications

A cell-microelectronic sensing technique for the screening of cytoprotective compounds

A cell-microelectronic sensing technique for the screening of cytoprotective compounds

New bis(thiosemicarbazonate) gold(III) complexes inhibit HIV replication at cytostatic concentrations: Potential for incorporation into virostatic cocktails

A Real-time Electrical Impedance Based Technique to Measure Invasion of Endothelial Cell Monolayer by Cancer Cells

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