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Ultra-low noise system to detect membrane capacitive currents of C6 Glioma cells

Paulo R. Rocha1* and Dago De Leeuw2
  • 1 University of Bath, Department of Electronic & Electrical Engineering, United Kingdom
  • 2 Delft University of Technology, Netherlands

Recording minuscule electrical activity of cell populations is currently a major technical challenge to electrophysiology. For this purpose we built an extremely low-noise measuring system. The sensing system comprises a bidirectional transducer based on a metal/Si/SiO2/interdigitated gold electrode. The highly doped Si substrate can be used as a common gate to stimulate the cells. In order to reduce external interferences the transducer was located inside an incubator and all the instrumentation shielded by a faraday’s cage. The background noise level with only cell culture medium was less than 100 fA. [1-3] Bioelectric activity is recorded by measuring the capacitive current using zero bias at the electrodes. To validate the extreme sensitivity of the measuring system, we investigated the electrical activity of large populations of two cell lines known to be electrically quiescent. The cell lines studied were the human cervix carcinoma cell line, HeLa, and C6 glioma cells. HeLa cells are supposed to be electrically quit as they don’t originate from the brain or any other electrically excitable tissue. However, due to the high sensitivity of our measurement system, even the HeLa cells demonstrate fluctuations of their basal current level, which is much higher in amplitude than the background acquisition noise. The low frequency analysis of the HeLa cells reveals clear current fluctuations of about 3 pA. [3] Non-neuronal cell types such as glia and their transformed counterparts, glioma cells, exhibit distinctive single-cell oscillations in membrane potential, which are highly functional and coordinated. However, measurement of their subtle electrical activity is typically hampered by the high background noise. Here we demonstrate that we can detect the electrical behavior of entire large cell populations of C6 glioma cells without any physical disruption or interference into their physiology. Malfunctioning glioma cells can develop to brain tumors. Glioma patients often suffer from epileptic seizures due to the tumors impact on brain electrophysiology. Here we show that seizure-like events in glioma cells spontaneously appear and evolve from a few pA to more than 100 pA on a time scale of hours. A direct correlation between electrical bursting and extracellular pH reduction was accomplished. Furthermore, at constant pH levels, a current noise analysis could determine that the glioma cell activity is primarily caused by the opening of voltage-gated Na+ and K+ ion channels and can be efficiently abolished using specific pharmacological inhibitors. We argue that our measuring system is unique to study electrophysiological properties of large cancer cell populations as an in vitro reference for tumor bulks in vivo.

References

1. P. R. F. Rocha, M. C. R. Medeiros, U. Kintzel, J. Vogt, Inês M. Araújo, A. L. G. Mestre, V. Mailänder, P. Schlett, M. Dröge, L. Schneider, F. Biscarini, D. M. de Leeuw, H. L. Gomes, “Extracellular electrical recording of pH-triggered bursts in C6 glioma cell populations”, Sci. Adv., 2, e1600516 (2016)

2. P. R. F. Rocha, P. Schlett, U. Kintzel, V. Mailänder, L. K. J. Vandamme, G. Zeck, H. L. Gomes, F. Biscarini, and D. M. de Leeuw, “Electrochemical noise and impedance of Au electrode/electrolyte interfaces enabling extracellular detection of glioma cell populations”, Sci. Rep., 6, 34843 (2016)

3. P. R. F. Rocha, P. Schlett, L. Schneider, M. Dröge, V. Mailänder, H. L. Gomes, P. W. M. Blom and D. M. de Leeuw, “Low frequency electric current noise in glioma cell populations”, J. Mater. Chem. B, J. Mater. Chem. B, 3, 5035-5039 (2015)

Keywords: ASICs, glia, bioelectronics, C6 glioma, extracellular recordings

Conference: MEA Meeting 2018 | 11th International Meeting on Substrate Integrated Microelectrode Arrays, Reutlingen, Germany, 4 Jul - 6 Jul, 2018.

Presentation Type: Oral Presentation

Topic: Microelectrode Array Technology

Citation: Rocha PR and De Leeuw D (2019). Ultra-low noise system to detect membrane capacitive currents of C6 Glioma cells. Conference Abstract: MEA Meeting 2018 | 11th International Meeting on Substrate Integrated Microelectrode Arrays. doi: 10.3389/conf.fncel.2018.38.00101

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Received: 01 Mar 2018; Published Online: 17 Jan 2019.

* Correspondence: Dr. Paulo R Rocha, University of Bath, Department of Electronic & Electrical Engineering, Bath, United Kingdom, procha@uc.pt