A major goal of electrode fabrication for application in microelectrode array (MEA) technology for extracellular cell signal recordings is to achieve low impedance because it results in a higher signal-to-noise ratio (SNR). Therefore, research has been focused on increasing the effective surface area by modifying the electrode with porous conducting materials, nanostructures, carbon nanotubes, and conducting polymers. [1-3].
This contribution shows that the detection limit of extracellular electrodes can be brought down to few nanovolts. Bioelectrical signals with amplitudes of 150 nanovolts in a noise level of 20 nanovolts (peak-to-peak) with a SNR >7 were recorded using PEDOT:PSS electrodes. The strategy behind this ultra-high sensitivity is the use of high capacitive electrodes and observation windows below 10 Hz. Our methodology is not suited to measure fast action potentials produced by neurons but allows the observation of weak and low frequency biological signals that have remain inaccessible using extracellular electrodes. The electrodes and the methodology are demonstrated by recording ultra-weak signals produced by primary cultures of astrocytes and glioma cell cultures. Our recording are confirmed by optical fluorescence recordings carried out in parallel and in line with previous reports in literature confirming that these cells produce signals in the scale of a several seconds up to minutes.
Here, we also show that for low frequency signals (f<1Hz) it is advantageous to measure the signals using current amplification methods. We observed that in voltage amplification the low frequency 1/f noise contribution increases rapidly and tends evolve to 1/f2 dependence. This effect degrades the SNR when measurements are carried out using voltage amplification. In contrast when measurements are carried out in current amplification the intrinsic electrode noise is relatively flat at low frequencies. Polymer electrodes with a capacitance of 50 μF/cm2 (at 100 Hz) can easily record extracellular signals with a SNR=30 with a detection limited controlled by an electrode noise of only 0.1 pico-amp at 1Hz. This represents an improved sensitivity relative to previously published results.
Acknowledgments
This work received financial support from the Portuguese Foundation for Science and Technology (FCT), through the project the projects “Implantable organic devices for advanced therapies (INNOVATE PTDC/EEI-AUT/5442/2014 and trough the Institute of Telecommunications.

References
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[3] Gooding, J. J., Lai, L. M. H. and Goon, I. Y. (2009) Nanostructured Electrodes with Unique Properties for Biological and other Applications, in Chemically Modified Electrodes, Volume 11 (eds R. C. Alkire, D. M. Kolb, J. Lipkowski and P. N. Ross), Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, Germany. doi: 10.1002/9783527627059.ch1