Kay J. Krause

Nanoscale Electrochemical Sensor Arrays: Redox Cycling Amplification in Dual-Electrode Systems

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 emerging fabrication technologies based on printed electronics that we believe have the potential of transforming current redox cycling concepts from laboratory tools for fundamental studies and proof-of-principle analytical demonstrations into high-throughput devices for rapid screening applications.

Noise phenomena caused by reversible adsorption in nanoscale electrochemical devices.

We theoretically investigate reversible adsorption in electrochemical devices on a molecular level. To this end, a computational framework is introduced, which is based on 3D random walks including probabilities for adsorption and desorption events at surfaces. We demonstrate that this approach can be used to investigate adsorption phenomena in electrochemical sensors by analyzing experimental noise spectra of a nanofluidic redox cycling device. The evaluation of simulated and experimental results reveals an upper limit for the average adsorption time of ferrocene dimethanol of ∼200 μs. We apply our model to predict current noise spectra of further electrochemical experiments based on interdigitated arrays and scanning electrochemical microscopy. Since the spectra strongly depend on the molecular adsorption characteristics of the detected analyte, we can suggest key indicators of adsorption phenomena in noise spectroscopy depending on the geometric aspect of the experimental setup.

Stochastic On-Chip Detection of Subpicomolar Concentrations of Silver Nanoparticles

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.

The Influence of Supporting Ions on the Electrochemical Detection of Individual Silver Nanoparticles : Understanding the Shape and Frequency of Current Transients in Nano-impacts

We report the influence of electrolyte composition and concentration on the stochastic amperometric detection of individual silver nanoparticles at microelectrode arrays and show that the sensor response at certain electrode potentials is dependent on both the conductivity of the electrolyte and the concentration of chloride ions. We further demonstrate that the chloride concentration in solution heavily influences the characteristic current spike shape of recorded nanoparticle impacts: While typically too short to be resolved in the measured current, the spike widths are significantly broadened at low chloride concentrations below 10 mm and range into the millisecond regime. The analysis of more than 25 000 spikes reveals that this effect can be explained by the diffusive mass transport of chloride ions to the nanoparticle, which limits the oxidation rate of individual silver nanoparticles to silver chloride at the chosen electrode potential.

How many molecules are required to obtain a steady faradaic current from mediated electron transfer at a single nanoparticle on a supporting surface

We investigate the chronoamperometric noise characteristics of electron-transfer reactions occurring on single nanoparticles (NPs) and assemblies of well-separated NPs on a supporting surface. To this end, we combine a formerly described expression for the steady-state current of a single particle with the shot-noise model and derive an expression for the signal-to-noise ratio as a function of bulk concentration and particle radius. Our findings are supported by random-walk simulations, which closely match the analytical results.

Three-dimensional inkjet-printed redox cycling sensor

Multilayer inkjet printing is emerging as a robust platform for fabricating flexible electronic devices over a large area. Here, we report a straightforward, scalable and inexpensive method for printing multilayer three-dimensional nanoporous redox cycling devices with a tunable nanometer gap for electrochemical sensing. The fabrication of the electrochemical redox cycling device is based on vertical stacking of two conductive electrodes made of carbon and gold nanoparticle inks. In this configuration, the two electrodes are parallel to each other and electrically separated by a layer of polystyrene nanospheres. As the top and the bottom electrodes are biased to, respectively, oxidizing and reducing potentials, repetitive cycling of redox molecules between them generates a large current amplification. We show that a vertical interelectrode spacing down to several hundred nanometers with high precision using inkjet printing is possible. The printed sensors demonstrate excellent performance in electrochemical sensing of ferrocene dimethanol as a redox-active probe. A collection efficiency of 100% and current amplification up to 30-fold could be obtained. Our method provides a low cost and versatile means for sensitive electrochemical measurements eliminating the need for sophisticated fabrication methods, which could prove useful for sensitive point-of-care diagnostics devices.

Influence of Self-Assembled Alkanethiol Monolayers on Stochastic Amperometric On-Chip Detection of Silver Nanoparticles

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.

Flexible Microgap Electrodes by Direct Inkjet Printing for Biosensing Application

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.

MEAs and 3D nanoelectrodes: electrodeposition as tool for a precisely controlled nanofabrication

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.

On-Chip Stochastic Detection of Silver Nanoparticles without a Reference Electrode

We report the electrochemical detection of 20 nm silver nanoparticles at a chip-based microelectrode array (MEA) without the need for a conventional reference electrode. This is possible due to the systems open-circuit potential allowing the oxidation of silver nanoparticles in the presence of phosphate-buffered saline (PBS). The hypothesis is confirmed by modulating the open-circuit potential via addition of ascorbic acid in solution, effectively inhibiting the detection of silver nanoparticle events. Employing the reference-free detection concept, we observe a linear relationship between the nanoparticle impact frequency at the microelectrodes and the nanoparticle concentration. This allows for viable quantification of silver nanoparticle concentrations in situ. The presented concept is ideal for the development of simple lab-on-a-chip or point-of-use systems enabling fast and low-cost screening of nanoparticles.