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. 2021 Sep 18;11(9):345.
doi: 10.3390/bios11090345.

Evaluation of Cancer Cell Lines by Four-Point Probe Technique, by Impedance Measurements in Various Frequencies

Georgia Paivana  1 , Dimitris Barmpakos  2 , Sophie Mavrikou  1 , Alexandros Kallergis  2 , Odysseus Tsakiridis  2 , Grigoris Kaltsas  2 , Spyridon Kintzios  1
Affiliations

Evaluation of Cancer Cell Lines by Four-Point Probe Technique, by Impedance Measurements in Various Frequencies

Georgia Paivana et al. Biosensors (Basel). .

Abstract

Cell-based biosensors appear to be an attractive tool for the rapid, simple, and cheap monitoring of chemotherapy effects at a very early stage. In this study, electrochemical measurements using a four-point probe method were evaluated for suspensions of four cancer cell lines of different tissue origins: SK-N-SH, HeLa, MCF-7 and MDA-MB-231, all for two different population densities: 50 K and 100 K cells/500 μL. The anticancer agent doxorubicin was applied for each cell type in order to investigate whether the proposed technique was able to determine specific differences in cell responses before and after drug treatment. The proposed methodology can offer valuable insight into the frequency-dependent bioelectrical responses of various cellular systems using a low frequency range and without necessitating lengthy cell culture treatment. The further development of this biosensor assembly with the integration of specially designed cell/electronic interfaces can lead to novel diagnostic biosensors and therapeutic bioelectronics.

Keywords: cancer cell lines; cell-based biosensor; doxorubicin; four-point probe measurements; polydimethylsiloxane.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Experimental setup: (a) The glass tube is placed on the PCB including the four-electrode configuration. The PDMS layer is placed on the bottom of the tube, covering half of the electrodes, allowing the addition of the cell culture on the top; (b) cross-section of the experimental setup.
Figure 2
Figure 2
Equivalent electrical circuit for cell suspension in buffer.
Figure 3
Figure 3
The Howland Pump circuit implemented using an AD8276 and a current buffer (AD8603), Adapted from Ref. [45].
Figure 4
Figure 4
System block diagram.
Figure 5
Figure 5
Graphic representation of the viability percentages of SK-N-SH, HeLa, MCF-7 and MDA-MB-231 cell lines before (blue columns) and after 30 min treatment with the anticancer agent doxorubicin (orange columns). * p < 0.05, *** p < 0.001 significantly different from the untreated control cells.
Figure 6
Figure 6
Morphological changes in the SK-N-SH (a,b), HeLa (c,d), MCF-7 (e,f) and MDA-MB-231 (g,h) cell lines before (first row) and after (second row) DOX treatment respectively. Scale bars = 50 μm.
Figure 7
Figure 7
Mean impedance values of cell lines before and after treatment with the anticancer agent doxorubicin in two different population densities (50 K cells and 100 K cells/500 μL) in five different frequencies (5, 10, 100, 250, 500 and 1000 Hz): (a) SK-N-SH; (b) HeLa, (c) MCF-7; (d) MDA-MB-231.
Figure 7
Figure 7
Mean impedance values of cell lines before and after treatment with the anticancer agent doxorubicin in two different population densities (50 K cells and 100 K cells/500 μL) in five different frequencies (5, 10, 100, 250, 500 and 1000 Hz): (a) SK-N-SH; (b) HeLa, (c) MCF-7; (d) MDA-MB-231.
Figure 8
Figure 8
ΔZ/Z0 (%) for four cell lines in six different frequencies (10, 50, 100, 250, 500, and 1000 Hz) for two different population densities (50 K cells and 100 K cells/500 μL) before and after treatment with the anticancer agent doxorubicin: (a) SK-N-SH; (b) HeLa; (c) MCF-7; (d) MDA-MB-231.
Figure 9
Figure 9
ΔZ/Z0 (%) for cell lines before and after treatment with the anticancer agent doxorubicin in two different population densities (50 K cells and 100 K cells/500 μL) in five different frequencies (5, 10, 100, 250, 500 and 1000 Hz): (a) SK-N-SH; (b) HeLa; (c) MCF-7; (d) MDA-MB-231.
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