Application of Impedance-Based Techniques in Hepatology Research

Morgan, Katie; Gamal, Wesam; Samuel, Kay; Morley, Steven D.; Hayes, Peter; Bagnaninchi, Pierre O.; Plevris, John

doi:10.3390/jcm9010050

Cited by 16 publications

(16 citation statements)

References 73 publications

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“…The documented research applications of RTCA include the toxicological studies, specifically the research on myocardial toxicity [37], and the screening of the toxicity of engineered nanoparticle bio-conjugates [38]. Furthermore, the RTCA application was reported in the hepatological field [39], as well as in traditional Chinese herbal medicine [40].…”

Section: Acea Xcelligence ® Real-time Cell Analysis (Rtca)mentioning

confidence: 99%

In Vitro Methods for Measuring the Permeability of Cell Monolayers

Bednarek

2022

MPs

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Cell monolayers, including endothelial and epithelial cells, play crucial roles in regulating the transport of biomolecules to underlying tissues and structures via intercellular junctions. Moreover, the monolayers form a semipermeable barrier across which leukocyte transmigration is tightly regulated. The inflammatory cytokines can disrupt the epithelial and endothelial permeability, thus the reduced barrier integrity is a hallmark of epithelial and endothelial dysfunction related with numerous pathological conditions, including cancer-related inflammation. Therefore, the assessment of barrier function is critical in in vitro models of barrier-forming tissues. This review summarizes the commercially available in vitro systems used to measure the permeability of cellular monolayers. The presented techniques are separated in two large groups: macromolecular tracer flux assays, and electrical impedance measurement-based permeability assays. The presented techniques are briefly described and compared.

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Section: Acea Xcelligence ® Real-time Cell Analysis (Rtca)mentioning

confidence: 99%

In Vitro Methods for Measuring the Permeability of Cell Monolayers

Bednarek

2022

MPs

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“…Morgan et al described the potential of impedance-based techniques in hepatology research and have identified the main platforms used for impedance-based cell analysis with hepatocytes in monolayer cultures in vitro. The application of these techniques in vitro and ex vivo to 3D structures still needs to be addressed and would be an important breakthrough [ 7 ]. Previous work on the electrical characterization of hepatic tissue has focused on cancerous tissue [ 8 ] or liver steatosis [ 9 , 10 ], while liver fibrosis has been less explored.…”

Section: Introductionmentioning

confidence: 99%

Electrical Impedance-Based Characterization of Hepatic Tissue with Early-Stage Fibrosis

et al. 2022

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Liver fibrosis is a key pathological precondition for hepatocellular carcinoma in which the severity is confidently correlated with liver cancer. Liver fibrosis, characterized by gradual cell loss and excessive extracellular matrix deposition, can be reverted if detected at the early stage. The gold standard for staging and diagnosis of liver fibrosis is undoubtedly biopsy. However, this technique needs careful sample preparation and expert analysis. In the present work, an ex vivo, minimally destructive, label-free characterization of liver biopsies is presented. Through a custom-made experimental setup, liver biopsies of bile-duct-ligated and sham-operated mice were measured at 8, 15, and 21 days after the procedure. Changes in impedance were observed with the progression of fibrosis, and through data fitting, tissue biopsies were approximated to an equivalent RC circuit model. The model was validated by means of 3D hepatic cell culture measurement, in which the capacitive part of impedance was proportionally associated with cell number and the resistive one was proportionally associated with the extracellular matrix. While the sham-operated samples presented a decrease in resistance with time, the bile-duct-ligated ones exhibited an increase in this parameter with the evolution of fibrosis. Moreover, since the largest difference in resistance between healthy and fibrotic tissue, of around 2 kΩ, was found at 8 days, this method presents great potential for the study of fibrotic tissue at early stages. Our data point out the great potential of exploiting the proposed needle setup in clinical applications.

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“…Among these methods, DS is a non-invasive, fast, and promising method for cell screening. DS has been widely used for impedance measurements of yeast cells [10][11][12], breast cancer cells [13], lymphocyte activation profiling [14], monitoring performance of epithelial tissues [15], and hepatology research [16].…”

Section: Introductionmentioning

confidence: 99%

A Microfluidic Dielectric Spectroscopy System for Characterization of Biological Cells in Physiological Media

Bakhtiari

Manshadi

Mansoorifar

et al. 2022

Sensors

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Dielectric spectroscopy (DS) is a promising cell screening method that can be used for diagnostic and drug discovery purposes. The primary challenge of using DS in physiological buffers is the electrode polarization (EP) that overwhelms the impedance signal within a large frequency range. These effects further amplify with the miniaturization of the measurement electrodes. In this study, we present a microfluidic system and the associated equivalent circuit models for real-time measurements of cell membrane capacitance and cytoplasm resistance in physiological buffers with 10 s increments. The current device captures several hundreds of biological cells in individual microwells through gravitational settling and measures the system’s impedance using microelectrodes covered with dendritic gold nanostructures. Using PC-3 cells (a highly metastatic prostate cancer cell line) suspended in cell growth media (CGM), we demonstrate stable measurements of cell membrane capacitance and cytoplasm resistance in the device for over 15 min. We also describe a consistent application of the equivalent circuit model, starting from the reference measurements used to determine the system parameters. The circuit model is tested using devices with varying dimensions, and the obtained cell parameters between different devices are nearly identical. Further analyses of the impedance data have shown that accurate cell membrane capacitance and cytoplasm resistance can be extracted using a limited number of measurements in the 5 MHz to 10 MHz range. This will potentially reduce the timescale required for real-time DS measurements below 1 s. Overall, the new microfluidic device can be used for the dielectric characterization of biological cells in physiological buffers for various cell screening applications.

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Application of Impedance-Based Techniques in Hepatology Research

Cited by 16 publications

References 73 publications

In Vitro Methods for Measuring the Permeability of Cell Monolayers

In Vitro Methods for Measuring the Permeability of Cell Monolayers

Electrical Impedance-Based Characterization of Hepatic Tissue with Early-Stage Fibrosis

A Microfluidic Dielectric Spectroscopy System for Characterization of Biological Cells in Physiological Media

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