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

Abstract

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...

Fabrication of a Horizontal and a Vertical Large Surface Area Nanogap Electrochemical Sensor

“…Large area nanogap devices offer an exciting platform to explore direct capacitive/dielectric detection of biomolecules, as well as other direct electrochemical detection techniques, such as redox cycling signal amplification [29,45]. The fabrication processes presented for both vertical and horizontal coplanar, large-area, nanogap devices can be readily explored for the development of a wide range of geometries and (bio)sensing applications.…”

“…The majority of longer horizontal nanogap devices are fabricated using either EBL or FIB. Vertical nanogap devices for electrochemical sensing applications have, in particular, been pioneered by the groups of both Lemay [19,20,26] and Wolfrum [19,20,27,28,29]. By far the most popular method for the fabrication of vertical nanogap devices involves etching away a sacrificial layer between two electrode layers.…”

Micro/nanoelectrochemical probe and chip devices for evaluation of three-dimensional cultured cells

“…In addition to planar electrodes, nanogap devices with electrode pairs have been proposed for redox cycling-based signal amplification and selective assays. 40,41 In addition to electrodes, microwells and microfluidics are incorporated into the devices for trapping cells, manipulating cells, and accumulating target molecules. Several kinds of electrode array devices have been reported for microarray detection, 42 and the present review focuses on the chip devices for evaluation of 3D cultured cells.…”

Miniaturized Biamperometric Detectors for Electrochemical Detection in Flowing Streams

“…There are also a few reports on biamperometric determination of catecholamine neurotransmitters; however, indirect methods were developed only [11,12,23,24]. Very simple instrumentational setup, 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 easy miniaturization of electrodes for microfluidic devices [25] and current amplification by redox cycling at microelectrodes and interdigitated arrays [10,26] are major advantages of its use nowadays. In this contribution, we tested the possibilities of different configurations of simple microelectrode detectors for biamperometric monitoring of dopamine and norepinephrine as model neurotransmitters.…”