Electrode–Electrolyte Interface Impedance Characterization of Ultra-Miniaturized Microelectrode Arrays Over Materials and Geometries for Sub-Cellular and Cellular Sensing and Stimulation

Impedance Characterization and Modeling of Subcellular to Micro-sized Electrodes with Varying Materials and PEDOT:PSS Coating for Bioelectrical Interfaces

“…PEDOT:PSS/ITO and PEDOT:PSS/TiN electrodes exhibited different impedances from each other, PEDOT:PSS/Au, and PEDOT:PSS/Pt due to bare ITO and TiN electrodes displaying unique impedances over frequency. For the same electrode size with different materials without PEDOT:PSS coating, ITO exhibited the highest interfacial impedance followed by Au, Pt, and TiN, in good agreement with previous studies, ,,, which can be explained to their differences in interfacial capacitances. At a low frequency, ITO, Au, and Pt electrodes with D ≤ 200 μm behaved mostly capacitively as reflected with a near −90° phase at f ≤ 1 kHz, implicating that the impedance was dominated by the capacitive coupling of the material and rendered the solution resistance negligible.…”

“…These applications have broad and profound impacts including broadening fundamental understanding of biological processes through organ-on-chip devices, − treating brain injuries via neuroprosthesis, − and accelerating drug discovery with multi-modal cell-based sensors. − The electrode–cell/–tissue interfaces enable spatiotemporal recording of various cellular signals, for example, intra-/extra-cellular potentials, local field potentials (LFPs), cell–cell/cell–surface impedances, as well as bioelectrical stimulation and a wide variety of electrochemical reactions. ,,,,− For intimate monitoring of cellular parameters, there is a considerably growing interest in improving spatiotemporal resolution, increasing the total field-of-view (FoV), minimizing the device invasiveness, and boosting the number of simultaneous parallel readout channels. , Consequently, enhancing spatial resolution entails aggressively trimming the electrode sizes toward subcellular features (<5 μm) and scaling the total FoV to the tissue-level monitoring (>2–3 mm), a feat that requires extremely dense yet large-scale microelectrode arrays (MEAs) on rigid or flexible substrates with high reliability. However, such extreme miniaturization of electrodes inevitably limits the electrodes’ electrochemically active area and drastically increases the electrode–electrolyte or electrode–cell interfacial impedance. , The increased interfacial impedance directly raises thermal noise that deteriorates interface SNR and consequently constrains any electrical or electrochemical detection. , Furthermore, many in vivo (e.g., pacemakers and neuroprosthetics) and in vitro (e.g., lab-on-chip devices with cell-based assays) applications demand low electrode–cell interfacial impedance to support cellular bioelectrical stimulation with minimal invasiveness. High interfacial impedance causes large voltage drops across the electrode–cell/–tissue interface that will diminish stimulation efficacy and may generate unwanted electrochemical reactions, resulting in both electrode degradation and tissue damage.…”

“…This will not only fundamentally enable the next-generation bioelectrical sensing and actuation but also implore the need to characterize electrodes of various sizes and materials/coatings at subcellular levels. Considerable studies on modeling the electrode–electrolyte interfaces have established our understanding of the effects of various electrode properties, such as electrode materials and sizes, on the biosensing and electrical stimulation through MEAs. ,,,− Previous investigations have also demonstrated that non-uniform distribution of current near edges of electrodes often causes early electrode degradations. ,, Recently, conducting polymer-coated electrodes have been considered as an ideal alternative to conventional metal or metal-oxide electrodes. ,, Particularly, PEDOT:PSS-coated electrodes (>10 μm) have been shown to significantly reduce the interfacial impedance and thermal noise while maintaining long-term electrochemical stability and excellent biocompatibility due to its mixed electronic/ionic conductivity. ,,− ,,− In addition, the elastic nature of PEDOT:PSS reduces the mechanical mismatch at the interface between electrodes and cells, enhancing devices’ biocompatibility and decreasing their invasiveness . However, despite several decades of research, the performance limitations, electrochemical characteristics, and electrode–electrolyte interfaces attributed to electrodes of varying compositions, sizes, and polymer coatings have not been systematically characterized, especially for electrodes of subcellular sizes that exhibit substantial edge-to-area ratios.…”

Bioimpedance Sensors: A Tutorial

“…The smaller their interface impedance, the smaller this error will be if there is a current flow, further ensuring that the amplifier input impedance is sufficiently high. The large voltage drop across the interface impedance further facilitates undesirable electrochemical reactions at the interface that can be harmful to biology [30], [58].…”

“…Large electrode impedance is also associated with higher electrode noise, further reducing SNR [58]- [60]. Stochastic fluctuations in ion transport led to thermal noise.…”