Paulo R. F. Rocha

Electrochemical noise and impedance of Au electrode/electrolyte interfaces enabling extracellular detection of glioma cell populations

Microelectrode arrays (MEA) record extracellular local field potentials of cells adhered to the electrodes. A disadvantage is the limited signal-to-noise ratio. The state-of-the-art background noise level is about 10 μVpp. Furthermore, in MEAs low frequency events are filtered out. Here, we quantitatively analyze Au electrode/electrolyte interfaces with impedance spectroscopy and noise measurements. The equivalent circuit is the charge transfer resistance in parallel with a constant phase element that describes the double layer capacitance, in series with a spreading resistance. This equivalent circuit leads to a Maxwell-Wagner relaxation frequency, the value of which is determined as a function of electrode area and molarity of an aqueous KCl electrolyte solution. The electrochemical voltage and current noise is measured as a function of electrode area and frequency and follow unambiguously from the measured impedance. By using large area electrodes the noise floor can be as low as 0.3 μVpp. The resulting high sensitivity is demonstrated by the extracellular detection of C6 glioma cell populations. Their minute electrical activity can be clearly detected at a frequency below about 10 Hz, which shows that the methodology can be used to monitor slow cooperative biological signals in cell populations.

Opto-electronic characterization of electron traps upon forming polymer oxide memory diodes

Metal-insulator-polymer diodes where the insulator is a thin oxide (Al2O3) layer are electroformed by applying a high bias. The initial stage is reversible and involves trapping of electrons near the oxide/polymer interface. The rate of charge trapping is limited by electron transport through the polymer. Detrapping of charge stored can be accomplished by illuminating with light under short-circuit conditions. The amount of stored charge is determined from the optically induced discharging current transient as a function of applied voltage and oxide thickness. When the charge density exceeds 8 × 1017/m2, an irreversible soft breakdown transition occurs to a non-volatile memory diode.

Lithium fluoride injection layers can form quasi-ohmic contacts for both holes and electrons

Thin LiF interlayers are typically used in organic light-emitting diodes to enhance the electron injection. Here, we show that the effective work function of a contact with a LiF interlayer can be either raised or lowered depending on the history of the applied bias. Formation of quasi-Ohmic contacts for both electrons and holes is demonstrated by electroluminescence from symmetric LiF/polymer/LiF diodes in both bias polarities. The origin of the dynamic switching is charging of electrically induced Frenkel defects. The current density–electroluminescence–voltage characteristics can qualitatively be explained. The interpretation is corroborated by unipolar memristive switching and by bias dependent reflection measurements.

Extracellular electrical recording of pH-triggered bursts in C6 glioma cell populations

Extracellular electrode recording demonstrates acid-triggered electrical activity in glioma cell populations. Glioma patients often suffer from epileptic seizures because of the tumor’s impact on the brain physiology. Using the rat glioma cell line C6 as a model system, we performed long-term live recordings of the electrical activity of glioma populations in an ultrasensitive detection method. The transducer exploits large-area electrodes that maximize double-layer capacitance, thus increasing the sensitivity. This strategy allowed us to record glioma electrical activity. We show that although glioma cells are nonelectrogenic, they display a remarkable electrical burst activity in time. The low-frequency current noise after cell adhesion is dominated by the flow of Na+ ions through voltage-gated ion channels. However, after an incubation period of many hours, the current noise markedly increased. This electric bursting phenomenon was not associated with apoptosis because the cells were viable and proliferative during the period of increased electric activity. We detected a rapid cell culture medium acidification accompanying this event. By using specific inhibitors, we showed that the electrical bursting activity was prompted by extracellular pH changes, which enhanced Na+ ion flux through the psalmotoxin 1–sensitive acid-sensing ion channels. Our model of pH-triggered bursting was unambiguously supported by deliberate, external acidification of the cell culture medium. This unexpected, acidosis-driven electrical activity is likely to directly perturb, in vivo, the functionality of the healthy neuronal network in the vicinity of the tumor bulk and may contribute to seizures in glioma patients.

Anomalous temperature dependence of the current in a metal-oxide-polymer resistive switching diode

Metal-oxide polymer diodes exhibit non-volatile resistive switching. The current–voltage characteristics have been studied as a function of temperature. The low-conductance state follows a thermally activated behaviour. The high-conductance state shows a multistep-like behaviour and below 300 K an enormous positive temperature coefficient. This anomalous behaviour contradicts the widely held view that switching is due to filaments that are formed reversibly by the diffusion of metal atoms. Instead, these findings together with small-signal impedance measurements indicate that creation and annihilation of filaments is controlled by filling of shallow traps localized in the oxide or at the oxide/polymer interface.

Low-frequency noise as a diagnostic tool for OLED reliability

Organic light emitting diodes (OLED), either based on polymers or small molecules, suffer from early failure: an unpredictable sudden increase in current with a total loss of light output. This work addresses this problem using small-signal impedance measurements and electrical noise techniques. Robust OLEDs show a current noise spectrum proportional to 1/f. OLEDs susceptible to failure have 1/f3/2 and/or may start exhibiting a standard 1/f behavior that rapidly evolves with time (typical 30 minutes) to 1/f1.6. In addition OLEDs susceptible to early failure have a higher DC leakage. It is proposed that a combination of both measurements can be used as a diagnostic tool for OLED reliability in a production line. Insight into the physics of the degradation mechanism is also provided. Unreliable OLEDs exhibit current switching events and optical blinks at wavelengths higher than the polymer band gap electroluminescence. It is proposed that degradation is induced by the appearance of an insulating resistive switching layer. Charge recombination trough this layer is responsible for the optical and electrical blinks.

The role of internal structure in the anomalous switching dynamics of metal-oxide/polymer resistive random access memories

The dynamic response of a non-volatile, bistable resistive memory fabricated in the form of Al2O3/polymer diodes has been probed in both the off- and on-state using triangular and step voltage profiles. The results provide insight into the wide spread in switching times reported in the literature and explain an apparently anomalous behaviour of the on-state, namely the disappearance of the negative differential resistance region at high voltage scan rates which is commonly attributed to a “dead time” phenomenon. The off-state response follows closely the predictions based on a classical, two-layer capacitor description of the device. As voltage scan rates increase, the model predicts that the fraction of the applied voltage, Vox , appearing across the oxide decreases. Device responses to step voltages in both the off- and on-state show that switching events are characterized by a delay time. Coupling such delays to the lower values of Vox attained during fast scan rates, the anomalous observation in the on-state that, device currents decrease with increasing voltage scan rate, is readily explained. Assuming that a critical current is required to turn off a conducting channel in the oxide, a tentative model is suggested to explain the shift in the onset of negative differential resistance to lower voltages as the voltage scan rate increases. The findings also suggest that the fundamental limitations on the speed of operation of a bilayer resistive memory are the time- and voltage-dependences of the switch-on mechanism and not the switch-off process.

Low frequency electric current noise in glioma cell populations

Measuring the electrical activity of large and defined populations of cells is currently a major technical challenge to electrophysiology, especially in the picoampere-range. For this purpose, we developed and applied a bidirectional transducer based on a chip with interdigitated gold electrodes to record the electrical response of cultured glioma cells. Recent research determined that also non-neural brain glia cells are electrically active and excitable. Their transformed counterparts, e.g. glioma cells, were suggested to partially retain these electric features. Such electrophysiological studies however are usually performed on individual cells and are limited in their predictive power for the overall electrical activity of the multicellular tumour bulk. Our extremely low-noise measuring system allowed us to detect not only prominent electrical bursts of neuronal cells but also minute, yet constantly occurring and functional, membrane capacitive current oscillations across large populations of C6 glioma cells, which we termed electric current noise. At the same time, tumour cells of non-brain origin (HeLa) proved to be electrically quiescent in comparison. Finally, we determined 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. Thus, we offer here a unique approach for studying electrophysiological properties of large cancer cell populations as an in vitro reference for tumour bulks in vivo.

Unipolar resistive switching in metal oxide/organic semiconductor non-volatile memories as a critical phenomenon

Diodes incorporating a bilayer of an organic semiconductor and a wide bandgap metal oxide can show unipolar, non-volatile memory behavior after electroforming. The prolonged bias voltage stress induces defects in the metal oxide with an areal density exceeding 1017 m−2. We explain the electrical bistability by the coexistence of two thermodynamically stable phases at the interface between an organic semiconductor and metal oxide. One phase contains mainly ionized defects and has a low work function, while the other phase has mainly neutral defects and a high work function. In the diodes, domains of the phase with a low work function constitute current filaments. The phase composition and critical temperature are derived from a 2D Ising model as a function of chemical potential. The model predicts filamentary conduction exhibiting a negative differential resistance and nonvolatile memory behavior. The model is expected to be generally applicable to any bilayer system that shows unipolar resistive switching.

Reversible post-breakdown conduction in aluminum oxide-polymer capacitors

Aluminum/Al2O3/polymer/metal capacitors submitted to a low-power constant current stress undergo dielectric breakdown. The post-breakdown conduction is metastable, and over time the capacitors recover their original insulating properties. The decay of the conduction with time follows a power law (1/t)α. The magnitude of the exponent α can be raised by application of an electric field and lowered to practically zero by optical excitation of the polyspirofluorene polymer. The metastable conduction is attributed to formation of metastable pairs of oppositely charged defects across the oxide-polymer interface, and the self-healing is related to resistive switching.