Microelectrode arrays (MEAs) provide promising opportunities to study electrical signals in neuronal and cardiac cell networks, restore sensory function, or treat disorders of the nervous system. Nevertheless, most of the currently investigated devices rely on silicon or polymer materials, which neither physically mimic nor mechanically match the structure of living tissue, causing inflammatory response or loss of functionality. Here, we present a new method for developing soft MEAs as bioelectronic interfaces. The functional structures are directly deposited on PDMS-, agarose-, and gelatin-based substrates using ink-jet printing as a patterning tool. We demonstrate the versatility of this approach by printing high-resolution carbon MEAs on PDMS and hydrogels. The soft MEAs are used for in vitro extracellular recording of action potentials from cardiomyocyte-like HL-1 cells. Our results represent an important step toward the design of next-generation bioelectronic interfaces in a rapid prototyping approach.npj Flexible Electronics (2018) 2:15 ;

Real-time investigations of neurotransmitter release provide a direct insight on the mechanisms involved in synaptic communication. Carbon fiber microelectrodes are state-of-the-art tools for electrochemical measurements of single vesicle neurotransmitter release. Yet, they lack high-throughput capabilities that are required for collecting robust statistically significant data across multiple samples. Here, we present a chip-based recording system enabling parallel in vitro measurements of individual neurotransmitter release events from cells, cultured directly on planar multielectrode arrays. The applicability of this cell-based platform to pharmacological screening is demonstrated by resolving minute concentration-dependent effects of the dopamine reuptake inhibitor nomifensine on recorded single-vesicle release events from PC12 cells. The experimental results, showing an increased half-time of the recorded events, are complemented by an analytical model for the verification of drug action.

Micro- and nanofabriation technologies have a tremendous potential for the development of powerful sensor array platforms for electrochemical detection. The ability to integrate electrochemical sensor arrays with microfluidic devices nowadays provides possibilities for advanced lab-on-a-chip technology for the detection or quantification of multiple targets in a high-throughput approach. In particular, this is interesting for applications outside of analytical laboratories, such as point-of-care (POC) or on-site water screening where cost, measurement time, and the size of individual sensor devices are important factors to be considered. In addition, electrochemical sensor arrays can monitor biological processes in emerging cell-analysis platforms. Here, recent progress in the design of disease model systems and organ-on-a-chip technologies still needs to be matched by appropriate functionalities for application of external stimuli and read-out of cellular activity in long-term experiments. Preferably, data can be gathered not only at a singular location but at different spatial scales across a whole cell network, calling for new sensor array technologies. In this Account, we describe the evolution of chip-based nanoscale electrochemical sensor arrays, which have been developed and investigated in our group. Focusing on design and fabrication strategies that facilitate applications for the investigation of cellular networks, we emphasize the sensing of redox-active neurotransmitters on a chip. To this end, we address the impact of the device architecture on sensitivity, selectivity as well as on spatial and temporal resolution. Specifically, we highlight recent work on redox-cycling concepts using nanocavity sensor arrays, which provide an efficient amplification strategy for spatiotemporal detection of redox-active molecules. As redox-cycling electrochemistry critically depends on the ability to miniaturize and integrate closely spaced electrode systems, the fabrication of suitable nanoscale devices is of utmost importance for the development of this advanced sensor technology. Here, we address current challenges and limitations, which are associated with different redox cycling sensor array concepts and fabrication approaches. State-of-the-art micro- and nanofabrication technologies based on optical and electron-beam lithography allow precise control of the device layout and have led to a new generation of electrochemical sensor architectures for highly sensitive detection. Yet, these approaches are often expensive and limited to clean-room compatible materials. In consequence, they lack possibilities for upscaling to high-throughput fabrication at moderate costs. In this respect, self-assembly techniques can open new routes for electrochemical sensor design. This is true in particular for nanoporous redox cycling sensor arrays that have been developed in recent years and provide interesting alternatives to clean-room fabricated nanofluidic redox cycling devices. We conclude this Account with a discussion of em...

We introduce the stochastic amperometric detection of silver nanoparticles on-chip using a microelectrode array. The technique combines the advantages of parallel and low-noise recordings at individually addressable microelectrodes. We demonstrate the detection of subpicomolar concentrations of silver nanoparticles with a diameter of 10 nm at sampling rates in the kilohertz regime for each channel. By comparison to random walk simulations, we show that the sensitivity of a single measurement is mainly limited by adsorption of nanoparticles at the surface of the chips and the measurement time.

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.