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A crucial parameter in the body-fluid analysis is Na+-ions. Preferably realized as a small wearable, mostly the fabrication method, size, and costs prevented ion-selective devices to enter the big realm of IoT applications. This letter reports a printed, electrochemical sensor system for measuring Na+-ions in liquids. We designed, simulated, optimized, fabricated, and experimentally evaluated the sensor structures. Employing electrochemical impedance spectroscopy on a printable, dielectric ion-selective membrane, reproducible 2-electrode-measurement results are achieved in a biological-relevant mM-range. The cross-sensitivity toward K+-ions, dynamic range, and drift are investigated, and a robust measurement scheme is derived. The flexible, low-cost approach can enable new Internet-of-Things and point-of-care applications in biomedicine such as sweat analysis and environmental monitoring.

Objective. Electrical measurement of the activity of individual neurons is a primary goal for many invasive neural electrodes. Making these ‘single unit’ measurements requires that we fabricate electrodes small enough so that only a few neurons contribute to the signal, but not so small that the impedance of the electrode creates overwhelming noise or signal attenuation. Thus, neuroelectrode design often must strike a balance between electrode size and electrode impedance, where the impedance is often assumed to scale linearly with electrode area. Approach and main results. Here we study how impedance scales with neural electrode area and find that the 1 kHz impedance of Pt electrodes (but not Au electrodes) transitions from scaling with area (r −2) to scaling with perimeter (r −1) when the electrode radius falls below 10 µm. This effect can be explained by the transition from planar to spherical diffusion behavior previously reported for electrochemical microelectrodes. Significance. These results provide important intuition for designing small, single unit recording electrodes. Specifically, for materials where the impedance is dominated by a pseudo-capacitance that is associated with a diffusion limited process, the total impedance will scale with perimeter rather than area when the electrode size becomes comparable with the diffusion layer thickness. For Pt electrodes this transition occurs around 10 µm radius electrodes. At even lower frequencies (1 Hz) impedance approaches a constant. This transition to r −1 scaling implies that electrodes with a pseudo-capacitance can be made smaller than one might expect before thermal noise or voltage division limits the ability to acquire high-quality single-unit recordings.

Recent investigations into cardiac or nervous tissues call for systems that are able to electrically record in 3D as opposed to 2D. Typically, challenging microfabrication steps are required to produce 3D microelectrode arrays capable of recording at the desired position within the tissue of interest. As an alternative, additive manufacturing is becoming a versatile platform for rapidly prototyping novel sensors with flexible geometric design. In this work, 3D MEAs for cell-culture applications were fabricated using a piezoelectric inkjet printer. The aspect ratio and height of the printed 3D electrodes were user-defined by adjusting the number of deposited droplets of silver nanoparticle ink along with a continuous printing method and an appropriate drop-to-drop delay. The Ag 3D MEAs were later electroplated with Au and Pt in order to reduce leakage of potentially cytotoxic silver ions into the cellular medium. The functionality of the array was confirmed using impedance spectroscopy, cyclic voltammetry, and recordings of extracellular potentials from cardiomyocyte-like HL-1 cells.

ObjectiveElectrical measurement of the activity of individual neurons is a primary goal for many invasive neural electrodes. Making these “single unit” measurements requires that we fabricate electrodes small enough so that only a few neurons contribute to the signal, but not so small that the impedance of the electrode creates overwhelming noise or signal attenuation. Thus, neuroelectrode design often must strike a balance between electrode size and electrode impedance, where the impedance is often assumed to scale linearly with electrode area.Approach and main resultsHere we study how impedance scales with neural electrode area and find that the 1 kHz impedance of Pt electrodes (but not Au electrodes) transitions from scaling with area (r-2) to scaling with perimeter (r-1) when the electrode radius falls below 10 microns. This effect can be explained by the transition from planar to spherical diffusion behavior previously reported for electrochemical microelectrodes. Significance: These results provide important intuition for designing small, single unit recording electrodes. Specifically, for materials where the impedance is dominated by a pseudo-capacitance that is associated with a diffusion limited process, the total impedance will scale with perimeter rather than area when the electrode size becomes comparable with the diffusion layer thickness. For Pt electrodes this transition occurs around 10 um radius electrodes. At even lower frequencies (1 Hz) impedance approaches a constant. This transition to r-1 scaling implies that electrodes with a pseudo-capacitance can be made smaller than one might expect before thermal noise or voltage division limits the ability to acquire high-quality single-unit recordings.

Microelectrode arrays (MEAs) are widely used platforms in bioelectronics to study electrogenic cells. In recent years, the processing of conductive polymers for the fabrication of three-dimensional electrode arrays has gained increasing interest for the development of novel sensor designs. Here, additive manufacturing techniques are promising tools for the production of MEAs with three-dimensional electrodes. In this work, a facile additive manufacturing process for the fabrication of MEAs that feature needle-like electrode tips, so-called μ-needles, is presented. To this end, an aerosol-jet compatible PEDOT:PSS and multiwalled carbon nanotube composite ink with a conductivity of 323 ± 75 S m-1 is developed and used in a combined inkjet and aerosol-jet printing process to produce the μ-needle electrode features. The μ-needles are fabricated with a diameter of 10 ± 2 μm and a height of 33 ± 4 μm. They penetrate an inkjet-printed dielectric layer to a height of 12 ± 3 μm. After successful printing, the electrochemical properties of the devices are assessed via cyclic voltammetry and impedance spectroscopy. The μ-needles show a capacitance of 242 ± 70 nF at a scan rate of 5 mV s-1 and an impedance of 128 ± 22 kΩ at 1 kHz frequency. The stability of the μ-needle MEAs in aqueous electrolyte is demonstrated and the devices are used to record extracellular signals from cardiomyocyte-like HL-1 cells. This proof-of-principle experiment shows the μ-needle MEAs' cell-culture compatibility and functional integrity to investigate electrophysiological signals from living cells.

Multielectrode arrays (MEAs) are versatile tools that are used for chronic recording and stimulation of neural cells and tissues. Driven by the recent progress in understanding of how neuronal growth and function respond to scaffold stiffness, development of MEAs with a soft cell-to-device interface has gained importance not only for in vivo but also for in vitro applications. However, the passivation layer, which constitutes the majority of the cell-device interface, is typically prepared with stiff materials. Herein, a fabrication of an MEA device with an ultrasoft passivation layer is described, which takes advantage of inkjet printing and a polydimethylsiloxane (PDMS) gel with a stiffness comparable to that of the brain. The major challenge in using the PDMS gel is that it cannot be patterned to expose the sensing area of the electrode. This issue is resolved by printing 3D micropillars at the electrode tip. Primary cortical neurons are grown on the fabricated device, and effective stimulation of the culture confirms functional cell-device coupling. The 3D MEA device with an ultrasoft interface provides a novel platform for investigating evoked activity and drug responses of living neuronal networks cultured in a biomimetic environment for both fundamental research and pharmaceutical applications.

Microelectrode arrays (MEAs) are state-of-the-art devices for extracellular recording and stimulation on biological tissue. Furthermore, they are a relevant tool for the development of biomedical applications like retina, cochlear and motor prostheses, cardiac pacemakers and drug screening. Hence, research on functional cell-sensor interfaces, as well as the development of new surface structures and modifications for improved electrode characteristics, is a vivid and well established field. However, combining single-cell resolution with sufficient signal coupling remains challenging due to poor cell-electrode sealing. Furthermore, electrodes with diameters below 20 µm often suffer from a high electrical impedance affecting the noise during voltage recordings. In this study, we report on a nanocavity sensor array for voltage-controlled stimulation and extracellular action potential recordings on cellular networks. Nanocavity devices combine the advantages of low-impedance electrodes with small cell-chip interfaces, preserving a high spatial resolution for recording and stimulation. A reservoir between opening aperture and electrode is provided, allowing the cell to access the structure for a tight cell-sensor sealing. We present the well-controlled fabrication process and the effect of cavity formation and electrode patterning on the sensor's impedance. Further, we demonstrate reliable voltage-controlled stimulation using nanostructured cavity devices by capturing the pacemaker of an HL-1 cell network.

Microelectrode arrays (MEAs) are gaining increasing importance for the investigation of signaling processes between electrogenic cells. However, efficient cell–chip coupling for robust and long-term electrophysiological recording and stimulation still remains a challenge. A possible approach for the improvement of the cell–electrode contact is the utilization of three-dimensional structures. In recent years, various 3D electrode geometries have been developed, but we are still lacking a fabrication approach that enables the formation of different 3D structures on a single chip in a controlled manner. This, however, is needed to enable a direct and reliable comparison of the recording capabilities of the different structures. Here, we present a method for a precisely controlled deposition of nanoelectrodes, enabling the fabrication of multiple, well-defined types of structures on our 64 electrode MEAs towards a rapid-prototyping approach to 3D electrodes.

Beilstein Journal of Nanotechnology 5, 1137-1143 (2014). doi:10.3762/bjnano.5.124, Published by Beilstein-Institut zur Förderung der Chemischen Wissenschaften, Frankfurt, M.

Fast scan cyclic voltammetry is a powerful technique for selective detection of biogenic amines in vivo and in vitro. Here we investigate this technique for multichannel spatiotemporal detection of neurotransmitter concentrations on a chip, using metal microelectrode arrays. The array-based approach allows monitoring concentration gradients of redox-active species at multiple highly localized (3 µm) positions simultaneously, while maintaining selectivity from the characteristic voltammogram shapes. We demonstrate that concentration fluctuations at individual electrode locations are resolved after spatially confined neurotransmitter injections. Furthermore, we discuss effects of microelectrode degradation caused by electrode sweeping during long-term experiments.

We simulate the amperometric response time of an interdigitated electrode array with respect to reversible adsorption of redox active molecules at the electrode surface. When neighboring electrodes are biased to potentials below and above the redox potential of the species under investigation, molecules can participate in repetitive reactions leading to an amplification of the Faradaic current. During collisions between molecules and electrodes, the molecules may undergo reversible adsorption. We simulate the behavior of this redox cycling process by using a discrete random walk model, which mimics the diffusive pathway of the molecules. Adsorption probabilities are implemented via the boundary conditions at the electrodes. Using this simulation, we investigate the effect of reversible adsorption on the response time of the interdigitated electrode array.

Nanocavity sensor arrays are powerful devices for parallel extracellular recordings of action potentials from cell networks. The sensors combine a high spatial resolution and seal resistance between cell and electrode with low electrode impedances, allowing low-noise electrophysiological measurements of individual cells in a network without the use of CMOS technology. In this paper, we present a new protocol for the simple fabrication of nanocavity sensors, which enables easy modification of standard microelectrode arrays. Our approach enables processing of devices with improved sensor characteristics and flexibility regarding electrode area and aperture size with minimal effort. We characterize the sensors by impedance spectroscopy and demonstrate their applicability by recording action potentials of individual cardiomyocyte-like cells growing in a network on the chip surface.

We describe the fabrication process and characterization of polymer coated multielectrode array chips featuring 64 planar Ag/AgCl electrodes for electrophysiological and electrochemical measurements of ionic currents. The multielectrode chip consists of platinum feedlines and microelectrodes fabricated on an oxidized silicon substrate. The feed lines are passivated with a polyimide layer. Silver is deposited electrochemically on the platinum electrodes and chlorinated afterwards resulting in stable micro Ag/AgCl reference electrodes that are recessed within picoliter cavities. We envisage the chip as a platform for high-throughput investigation of lipid bilayers. Schematics of a planar reference electrode. The chips are processed on oxidized silicon (blue) and consist of Pt feedlines (yellow), the Ag/AgCl electrode (black) passivated with polyimide (light blue).

Inkjet printing is an attractive method for cost-effective additive manufacturing of electronic devices. Especially for applications where disposable sensor systems are of interest, it is a promising tool since it enables the production of low-cost and flexible devices. In this work, we report the fabrication of a disposable microelectrode array (MEA) using solely inkjet printing technology. The MEAs were fabricated with two different functional inks, a self-made gold ink to print conductive feedlines and electrodes and a polymer-based ink to add a dielectric layer for insulation of the feedlines. We printed different MEA designs of up to 64 electrodes with a minimum lateral spacing of 200 μm and a minimum electrode diameter of ~31 μm. As a proof-of-concept, extracellular recordings of action potentials from cardiomyocyte-like HL-1 cells were performed using the all-printed devices. Furthermore, we stimulated the cells during the recordings with noradrenaline, which led to an increase in the recorded beating frequency of the cells. The results demonstrate the feasibility of inkjet printing gold MEAs for cell-based bioelectronics.

We investigate the influence of self-assembled alkanethiol monolayers at the surface of platinum microelectrode arrays on the stochastic amperometric detection of citrate-stabilized silver nanoparticles in aqueous solutions. The measurements were performed using a microelectrode array featuring 64 individually addressable electrodes that are recorded in parallel with a sampling rate of 10 kHz for each channel. We show that both the functional end group and the total length of the alkanethiol influence the charge transfer. Three different terminal groups, an amino, a hydroxyl, and a carboxyl, were investigated using two different molecule lengths of 6 and 11 carbon atoms. Finally, we show that a monolayer of alkanethiols with a length of 11 carbon atoms and a carboxyl terminal group can efficiently block the charge transfer of free nanoparticles in an aqueous solution.

We report the electrochemical detection of individual redox-active molecules as they freely diffuse in solution. Our approach is based on microfabricated nanofluidic devices, wherein repeated reduction and oxidation at two closely spaced electrodes yields a giant sensitivity gain. Single molecules entering and leaving the cavity are revealed as anticorrelated steps in the faradaic current measured simultaneously through the two electrodes. Cross-correlation analysis provides unequivocal evidence of single molecule sensitivity. We further find agreement with numerical simulations of the stochastic signals and analytical results for the distribution of residence times. This new detection capability can serve as a powerful alternative when fluorescent labeling is invasive or impossible. It further enables new fundamental (bio)electrochemical experiments, for example, localized detection of neurotransmitter release, studies of enzymes with redox-active products, and single-cell electrochemical assays. Finally, our lithography-based approach renders the devices suitable for integration in highly parallelized, all-electrical analysis systems.

We introduce both theoretically and experimentally a new electrochemical technique based on measuring the fluctuations of the faradaic current during redox cycling. By analogy with fluorescence correlation spectroscopy (FCS), we refer to this technique as electrochemical correlation spectroscopy (ECS). We first derive an analytical expression of the power spectral density for the fluctuations in a thin-layer-cell geometry. We then show agreement with measurements using ferrocenedimethanol, Fc(MeOH)2, in water and in acetonitrile in microfabricated thin-layer cells with a approximately 70 nm electrode spacing. The fluctuation spectra provide detailed information about the adsorption dynamics of Fc(MeOH)2, which cause an apparent slowing of Brownian motion. We furthermore observe high-frequency fluctuations from which we estimate the rates of adsorption and desorption.

Amperometric detection is ideally suited for integration into micro- and nanofluidic systems as it directly yields an electrical signal and does not necessitate optical components. However, the range of systems to which it can be applied is constrained by the limited sensitivity and specificity of the method. These limitations can be partially alleviated through the use of redox cycling, in which multiple electrodes are employed to repeatedly reduce and oxidize analyte molecules and thereby amplify the detected signal. We have developed an interdigitated electrode device that is encased in a nanofluidic channel to provide a hundred-fold amplification of the amperometric signal from paracetamol. Due to the nanochannel design, the sensor is resistant to interference from molecules undergoing irreversible redox reactions. We demonstrate this selectivity by detecting paracetamol in the presence of excess ascorbic acid.

Nanostructured surfaces have recently gained in importance for electrochemical applications because of an enhanced surface area compared to planar substrates. Due to this property, structured substrates are well suited for electrochemical (bio-)sensors, capacitive coupling with electrogenic cells, and other bioelectronic applications. However, the relationship between electrolytically exposed and redox-active surface areas of nanostructured electrodes compared to planar electrodes is still under discussion. Here, we performed a series of comparative studies to elucidate processes taking place at the electrochemically active surface of gold nanopillars. The pillars, approximately 200 nm in height and 50 nm in diameter, were fabricated using template-assisted nanostructuring. The surface area increase compared to planar electrodes was determined by scanning electron microscopy (SEM), and the redox-active surface area of the same sample was derived from cyclovoltammetric studies. We found consistency between the SEM results and the electrochemically active surfaces determined by cyclic voltammetry of immobilized ferrocenylhexanethiol, immobilized cytochrome c, and oxidation/reduction of gold for small scan rates. Similar values were derived from the capacitance measured by cyclic voltammetry, whereas impedimetric measurements revealed values twice as high. Commonly used diffusion-controlled systems, such as hexacyanoferrate, showed a smaller increase of the electroactive surface area. Finally, we conclude that the sterically restricted diffusion of redox-active species leads to an inaccurate determination of the electroactive surface area of nanosized electrodes.

We have developed a chip-based nanofluidic device to amplify the electrochemical signal of catechols by orders of magnitude. The amplification is based on rapid redox cycling between plane parallel electrodes inside a nanochannel. We show that it is possible to monitor the signal of only a few hundred molecules residing in the active area of the nanofluidic sensor. Furthermore, due to the nanochannel design, the sensor is immune to interference by molecules undergoing irreversible redox reactions. We demonstrate the selectivity of the device by detecting catechol in the presence of ascorbic acid, whose oxidized form is only stable for a short time. The interference of ascorbic acid is usually a challenge in the detection of catecholamines in biological samples.

A rapid fabrication method of microgap electrodes using inkjet printing is described. In this approach, the lateral spacing between two printed electrode lines is precisely controlled down to 1 µm without any surface modification or substrate patterning. The strong confinement, well below typical resolution of inkjet printing, relies on complete solvent evaporation between the printing of adjacent electrode structures, which is achieved by controlling the printing speed and temperature profiles. The feasibility of this method is demonstrated by writing electrode structures with two distinct inks, based on carbon and silver nanoparticles, with comparable results. As an application proof-of-principle, arrays of microgap electrodes are fabricated using a carbon nanoparticle ink for electrochemical detection based on redox-cycling, a technique in which the sensitivity of the device depends on the distance between the two electrodes. The redox-cycling amplification of electrochemical signals is demonstrated and it is shown that the printed microgap device can be used as an electrochemical biosensor for the determination of human immunodeficiency virus (HIV)-related single-stranded DNA. This work presents a promising new approach for fabricating low-cost and label-free redox-cycling biosensors using all-inkjet-printed electrodes.

We present a nanoporous dual-electrode device for highly sensitive electrochemical detection via redox cycling. The individual sensors comprise one billion nanopores in an area of 9 mm(2). Pores feature an approximate lateral distance of 100 nm and pore radii down below 20 nm. The sensor's fabrication process is based on porous alumina membranes, which are formed via anodization of aluminum films. Novel processing steps are combined enabling high-throughput fabrication of the nanoporous sensors on the wafer scale. In this context, we present an electrochemical approach for the selective passivation of nanostructured electrode areas and introduce an etching process with tuneable selectivity for the removal of titania versus alumina. The devices exhibit sensitivities of up to 330 μA mM(-1) for the redox-active probe Fe(CN)6(3-/4-) making use of highly efficient redox cycling amplification inside the nanopores. Furthermore, the large-scale interplay of the sensor's nanopores in millimetre dimensions facilitates analyte enrichment and depletion at the sensor surface. The large-area sensor therefore provides an interesting opportunity for determining the oxidation-state-dependent diffusion coefficients of redox-active molecules.

We computationally investigate the chronoamperometric current response of spherical and cubic particles on a supporting insulating surface. By using the method of finite differences and random walk simulations, we can show that both systems exhibit identical responses on all time scales if their exposed surface areas are equal. This result enables a simple and computationally efficient method to treat certain spherical geometries in random walk based noise investigations.

We introduce a novel device for the spatiotemporal detection of neurotransmitters on-chip. Our device features an array of individually addressable nanocavity sensors that utilize redox-cycling for the localized electrochemical determination of neurotransmitter concentrations. This effect is based on rapid, repeated redox-reactions between two closely spaced electrodes and results in a high amplification of the electrochemical signal of individual molecules. Each sensor is equipped with two independently biased electrodes that are separated by an ∼ 65 nm wide cavity, thus enabling efficient redox-cycling amplification. The sensors feature entry ports in the micrometer regime and can be closely packed for the chemical mapping at high spatial resolutions. In this paper, we present the devices capabilities in neurotransmitter detection. The sensors are electrochemically characterized and their functionality is demonstrated by measuring localized dopamine fluctuations in a microfluidic channel.

Electrochemical techniques rely on the stability of a defined reference potential. Due to the need for miniaturization, electrochemical lab-on-a-chip platforms often employ Ag/AgCl quasi-reference electrodes for this purpose. Here, we report on electrochemical artifacts resulting from nanoparticle–electrode collisions originating from standard chlorinated silver wires.

We present an optoelectrical device capable of in vitro optical stimulation and electrophysiological recording. The device consists of an array of micropixellated InGaN light-emitting diodes coupled to a custom-made ultrathin planar microelectrode array. Cells can be cultured directly on the chip for short- and long-term electrophysiological experiments. To show the functionality of the device, we transfected a cardiomyocyte-like cell line (HL-1) with a light-sensitive protein channelrhodopsin. We monitored action potentials of individual, spontaneously beating, HL-1 cells growing on the chip by extracellular electrical recordings. On-chip optical stimulation was demonstrated by triggering network activity in a confluent HL-1 cell culture and visualized by calcium imaging. We see the potential of our system for electrophysiological experiments with optogenetically modified cells. Optical stimulation can be performed directly on the chip without additional optical components or external light sources.

The ability to culture individual neurons and direct their connections on functional interfaces provides a platform for investigating information processing in neuronal networks. Numerous methods have been used to design ordered neuronal networks on microelectrode arrays (MEAs) for neuronal electrical activities recording. However, so far, no method has been implemented, which simultaneously provides high-resolution neuronal patterns and low-impedance microelectrode. To achieve this goal, we employed a chemical vapor-deposited, non-fouling poly (ethylene) glycol (PEG) self-assembled monolayer to provide a cell repellant background on the MEAs. Photolithography, together with plasma etching of the PEG monolayer, was used to fabricate different patterns on MEAs. No electrode performance degradation was observed after the whole process. Dissociated cortical neurons were cultured on the modified MEAs, and the patterns were maintained for more than 3 weeks. Spontaneous and evoked neuronal activities were recorded. All of the results demonstrate this surface engineering strategy allows successful patterning of neurons on MEAs, and is useful for future studies of information processing in defined neuronal networks on a chip.

We present a model to describe the response of chip-based nanocavity sensors during extracellular recording of action potentials. These sensors feature microelectrodes which are embedded in liquid-filled cavities. They can be used for the highly localized detection of electrical signals on a chip. We calculate the sensor's impedance and simulate the propagation of action potentials. Subsequently we apply our findings to analyze cell-chip coupling properties. The results are compared to experimental data obtained from cardiomyocyte-like cells. We show that both the impedance and the modeled action potentials fit the experimental data well. Furthermore, we find evidence for a large seal resistance of cardiomyocytes on nanocavity sensors compared to conventional planar recording systems.

We present a new biocompatible nanostructured microelectrode array for extracellular signal recording from electrogenic cells. Microfabrication techniques were combined with a template-assisted approach using nanoporous aluminum oxide to develop gold nanopillar electrodes. The nanopillars were approximately 300-400 nm high and had a diameter of 60 nm. Thus, they yielded a higher surface area of the electrodes resulting in a decreased impedance compared to planar electrodes. The interaction between the large-scale gold nanopillar arrays and cardiac muscle cells (HL-1) was investigated via focused ion beam milling. In the resulting cross-sections we observed a tight coupling between the HL-1 cells and the gold nanostructures. However, the cell membranes did not bend into the cleft between adjacent nanopillars due to the high pillar density. We performed extracellular potential recordings from HL-1 cells with the nanostructured microelectrode arrays. The maximal amplitudes recorded with the nanopillar electrodes were up to 100% higher than those recorded with planar gold electrodes. Increasing the aspect ratio of the gold nanopillars and changing the geometrical layout can further enhance the signal quality in the future.

We present a new nanocavity device for highly localized on-chip recordings of action potentials from individual cells in a network. Microelectrode recordings have become the method of choice for recording extracellular action potentials from high density cultures or slices. Nevertheless, interfacing individual cells of a network with high resolution still remains challenging due to an insufficient coupling of the signal to small electrodes, exhibiting diameters below 10 µm. We show that this problem can be overcome by a new type of sensor that features an electrode, which is accessed via a small aperture and a nanosized cavity. Thus, the properties of large electrodes are combined with a high local resolution and a good seal resistance at the interface. Fabrication of the device can be performed with state-of-the-art clean room technology and sacrificial layer etching allowing integration of the devices into sensor arrays. We demonstrate the capability of such an array by recording the propagation of action potentials in a network of cardiomyocyte-like cells.

Electrochemical mapping of neurotransmitter concentrations on a chip promises to be an interesting technique for investigating synaptic release in cellular networks. In here, we present a novel chip-based device for the detection of neurotransmitter fluctuations in real-time. The chip features an array of plane-parallel nanocavity sensors, which strongly amplify the electrochemical signal. This amplification is based on efficient redox cycling via confined diffusion between two electrodes inside the nanocavity sensors. We demonstrate the capability of resolving concentration fluctuations of redox-active species in a microfluidic mixing gradient on the chip. The results are explained by a simulated concentration profile that was calculated on the basis of the coupled Navier−Stokes and convection-diffusion equations using a finite element approach.

We demonstrate that a 50 nm high solution-filled cavity bounded by two parallel electrodes in which electrochemically active molecules undergo rapid redox cycling can be used to determine very fast electron-transfer kinetics. We illustrate this capability by showing that the heterogeneous rate constant of Fc(MeOH)(2) sensitively depends on the type and concentration of the supporting electrolyte. These solid-state devices are mechanically robust and stable over time and therefore have the potential to become a widespread and versatile tool for electrochemical measurements.

The design of electrode interfaces has a strong impact on cell-based bioelectronic applications. We present a new type of microelectrode array chip featuring a nanoporous alumina interface. The chip is fabricated in a combination of top-down and bottom-up processes using state-of-the-art clean room technology and self-assembled generation of nanopores by aluminum anodization. The electrode characteristics are investigated in phosphate buffered saline as well as under cell culture conditions. We show that the modified microelectrodes exhibit decreased impedance compared to planar microelectrodes, which is caused by a nanostructuring effect of the underlying gold during anodization. The stability and biocompatibility of the device are demonstrated by measuring action potentials from cardiomyocyte-like cells growing on top of the chip. Cross sections of the cell-surface interface reveal that the cell membrane seals the nanoporous alumina layer without bending into the sub-50 nm apertures. The nanoporous microelectrode array device may be used as a platform for combining extracellular recording of cell activity with stimulating topographical cues.