scholarly journals Dielectrophoretic and Electrical Impedance Differentiation of Cancerous Cells Based on Biophysical Phenotype

Biosensors ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 401
Author(s):  
Ina Turcan ◽  
Iuliana Caras ◽  
Thomas Gabriel Schreiner ◽  
Catalin Tucureanu ◽  
Aurora Salageanu ◽  
...  

Here, we reported a study on the detection and electrical characterization of both cancer cell line and primary tumor cells. Dielectrophoresis (DEP) and electrical impedance spectroscopy (EIS) were jointly employed to enable the rapid and label-free differentiation of various cancer cells from normal ones. The primary tumor cells that were collected from two colorectal cancer patients and cancer cell lines (SW-403, Jurkat, and THP-1), and healthy peripheral blood mononuclear cells (PBMCs) were trapped first at the level of interdigitated microelectrodes with the help of dielectrophoresis. Correlation of the cells dielectric characteristics that was obtained via electrical impedance spectroscopy (EIS) allowed evident differentiation of the various types of cell. The differentiations were assigned to a “dielectric phenotype” based on their crossover frequencies. Finally, Randles equivalent circuit model was employed for highlighting the differences with regard to a series group of charge transport resistance and constant phase element for cancerous and normal cells.

Micromachines ◽  
2020 ◽  
Vol 11 (9) ◽  
pp. 832
Author(s):  
Lexi Crowell ◽  
Juan Yakisich ◽  
Brian Aufderheide ◽  
Tayloria Adams

Electrical impedance spectroscopy (EIS) is an electrokinetic method that allows for the characterization of intrinsic dielectric properties of cells. EIS has emerged in the last decade as a promising method for the characterization of cancerous cells, providing information on inductance, capacitance, and impedance of cells. The individual cell behavior can be quantified using its characteristic phase angle, amplitude, and frequency measurements obtained by fitting the input frequency-dependent cellular response to a resistor–capacitor circuit model. These electrical properties will provide important information about unique biomarkers related to the behavior of these cancerous cells, especially monitoring their chemoresistivity and sensitivity to chemotherapeutics. There are currently few methods to assess drug resistant cancer cells, and therefore it is difficult to identify and eliminate drug-resistant cancer cells found in static and metastatic tumors. Establishing techniques for the real-time monitoring of changes in cancer cell phenotypes is, therefore, important for understanding cancer cell dynamics and their plastic properties. EIS can be used to monitor these changes. In this review, we will cover the theory behind EIS, other impedance techniques, and how EIS can be used to monitor cell behavior and phenotype changes within cancerous cells.


2021 ◽  
Author(s):  
Jose Montoya Mira ◽  
Ajay Sapre ◽  
Brett Walker ◽  
Jesus Bueno Alvarez ◽  
Kyle Gustafson ◽  
...  

Abstract Technologies that facilitate analyses of circulating biomarkers from blood for cancer detection are powerful tools for improving patient outcomes. Circulating biomarkers derived directly from the primary tumor have been identified including circulating tumor cells (CTCs) and circulating hybrid cells (CHCs), described to harbor phenotypes of both tumor cells and leukocytes. CHCs are present in higher numbers than CTCs which support their translational potential. Methods for isolation of CHCs do not exist and are restricted to low-throughput, time consuming, and biased methodologies. Here, we report development of a label-free dielectrophoretic (DEP) microfluidic platform facilitating enrichment of CHCs in a high-throughput and rapid fashion. Unlike other methods, depletion of healthy peripheral blood mononuclear cells (PBMCs) drives enrichment of CHCs. We analyzed DEP differential response of PBMCs and cancer cells and demonstrated up to 96.5% depletion of PBMCs resulting in 18.6-fold enrichment of cancer cells. In PBMCs from pancreatic adenocarcinoma patients, the platform enriched for neoplastic cells identified by their KRAS mutant status using droplet digital PCR from only 2 mL of whole blood with one hour of processing. Enrichment was achieved in 75% of the clinical samples analyzed, establishing this approach as a promising way to non-invasively analyze tumor cells from patients.


2021 ◽  
Author(s):  
Binying Yang ◽  
Jia Xu ◽  
Shao Hu ◽  
Boning You ◽  
Qing Ma

Abstract Background: Lead is a nonessential heavy metal, which can inhibit heme synthesis and has significant cytotoxic effects. Nevertheless, its effect on the electrical properties of red blood cells (RBCs) remains unclear. Consequently, this study aimed to investigate the electrical properties and the electrophysiological mechanism of lead exposure in mouse blood using Electrical Impedance Spectroscopy (EIS). Methods: AC impedance method was used to measure the electrical impedance of healthy and lead exposure blood of mice in 0.01-100 MHz frequency range. Data characteristic of the impedance spectrum, Bodes plot, Nyquist plot and Nichols plot, and three elements equivalent circuit model were used to explicitly analyze the differences in amplitude-frequency, phase-frequency, and the frequency characteristic of blood in electrical impedance properties. Results: Compared with the healthy blood in control mice, the changes in blood exposed to lead was as follows: (I) the hematocrit decreased; (II) the amplitude-frequency and phase-frequency characteristics of electrical impedance decreased; (III) the characteristic frequencies ( f 0 ) were significantly increased; (IV) the electrical impedance of plasma, erythrocyte membrane, and hemoglobin decreased, while the conductivity increased. Conclusion: Therefore, EIS can be used as an effective method to monitor blood and RBCs abnormalities caused by lead-exposure.


2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Jose Montoya Mira ◽  
Ajay A. Sapre ◽  
Brett S. Walker ◽  
Jesus Bueno Alvarez ◽  
Kyle T. Gustafson ◽  
...  

AbstractCellular circulating biomarkers from the primary tumor such as circulating tumor cells (CTCs) and circulating hybrid cells (CHCs) have been described to harbor tumor-like phenotype and genotype. CHCs are present in higher numbers than CTCs supporting their translational potential. Methods for isolation of CHCs do not exist and are restricted to low-throughput, time consuming, and biased methodologies. We report the development of a label-free dielectrophoretic microfluidic platform facilitating enrichment of CHCs in a high-throughput and rapid fashion by depleting healthy peripheral blood mononuclear cells (PBMCs). We demonstrated up to 96.5% depletion of PBMCs resulting in 18.6-fold enrichment of cancer cells. In PBMCs from pancreatic adenocarcinoma patients, the platform enriched neoplastic cells identified by their KRAS mutant status using droplet digital PCR with one hour of processing. Enrichment was achieved in 75% of the clinical samples analyzed, establishing this approach as a promising way to non-invasively analyze tumor cells from patients.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kian Kadan-Jamal ◽  
Aakash Jog ◽  
Marios Sophocleous ◽  
Julius Georgiou ◽  
Adi Avni ◽  
...  

AbstractAn improved approach for comparative study of plant cells for long term and continuous monitoring using electrical impedance spectroscopy is demonstrated for tomato and tobacco plant cells (MSK8 and BY2) in suspensions. This approach is based on the locations and magnitudes of defining features in the impedance spectra of the recently reported unified equivalent circuit model. The ultra-wide range (4 Hz to 20 GHz) impedance spectra of the cell lines were measured using custom probes, and were analyzed using the unified equivalent circuit model, highlighting significant negative phase peaks in the ~ 1 kHz to ~ 10 MHz range. These peaks differ between the tomato and tobacco cells, and since they can be easily defined, they can potentially be used as the signal for differentiating between different cell cultures or monitoring them over time. These findings were further analysed, showing that ratios relating the resistances of the media and the resistance of the cells define the sensitivity of the method, thus affecting its selectivity. It was further shown that cell agglomeration is also an important factor in the impedance modeling in addition to the overall cell concentration. These results can be used for optimizing and calibrating electrical impedance spectroscopy-based sensors for long term monitoring of cell lines in suspension for a given specific cell and media types.


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