Nouran Adly

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.

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.

Printed microfluidic filter for heparinized blood

A simple lab-on-a-chip method for blood plasma separation was developed by combining stereolithographic 3D printing with inkjet printing, creating a completely sealed microfluidic device. In some approaches, one dilutes the blood sample before separation, reducing the concentration of a target analyte and increasing a contamination risk. In this work, a single drop (8 μl) of heparinized whole blood could be efficiently filtered using a capillary effect without any external driving forces and without dilution. The blood storage in heparin tubes during 24 h at 4 °C initiated the formation of small crystals that formed auto-filtration structures in the sample upon entering the 3D-printed device, with pores smaller than the red blood cells, separating plasma from the cellular content. The total filtration process took less than 10 s. The presented printed plasma filtration microfluidics fabricated with a rapid prototyping approach is a miniaturized, fast and easy-to-operate device that can be integrated into healthcare/portable systems for point-of-care diagnostics.

Rapid Prototyping of Ultralow-Cost, Inkjet-Printed Carbon Microelectrodes for Flexible Bioelectronic Devices

Gaining better understanding of the human brain using chip‐based devices and promoting the recovery of lost biological functionality through implants are long pursued endeavors driven by advances in material science, bioelectronics, and the advancing silicon technology. While conventional bioelectronic and neuroelectronic devices typically rely on cleanroom‐based processing, a rapid prototyping technique is proposed that is based on high‐resolution inkjet printing featuring nanoporous carbon electrodes that yield excellent cell–chip coupling. This study aims to overcome two major limitations of conventional approaches that make the development of neuroelectronic devices very challenging and limit a wider use within the research community as well as industry: high costs and lack of rapid prototyping capabilities. These challenges are addressed with an all‐printed, high‐resolution approach that makes use of flexible polymer substrates and is fabricated on a fully digital printing platform. The manufacturing of a chip consumes less than 60 min and costs a few cents per chip. This study introduces nanoporous carbon as a cell‐interfacing electrode material that features outstanding properties for extracellular recording of action potentials and stimulation indicating that the printed carbon chips have the means to be used as a versatile neuroelectronic tool for in vitro and in vivo studies.

Printed microelectrode arrays on soft materials: from PDMS to hydrogels

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.Microelectrode arrays: ink-jet printing makes it simpleA cost-effective and simple approach to make soft microelectrode arrays has been developed using inkjet printing of carbon-based conductive ink. Prof Bernhard Wolfrum and his team from the Institute of Bioelectronics (ICS-8) at Forschungszentrum Jülich and the Munich School of Bioengineering at Technical University of Munich (TUM), Germany inkjet print functional sensor arrays on various soft substrates for bioelectronic applications. They print carbon nanoparticle conductive ink to fabricate high-resolution microelectrode arrays on PDMS and hydrogels. The soft microelectrode arrays are used for extracellular electrophysiological recordings of action potentials from HL-1 cells. The approach presented in their paper allows for rapid prototyping of disposable sensor array structures on a variety of soft substrates for in vitro as well as in vivo applications.