G. A. Kalkman, Y. Zhang, E. Monachino, K. Mathwig, M. E. Kamminga, P. Pourhossein, P. E. Oomen, S. A. Stratmann, Z. Zhao, A. M. van Oijen, E. M. J. Verpoorte and R. C. Chiechi Bisecting Microfluidic Channels with Metallic Nanowires Fabricated by Nanoskiving ACS Nano 10 (2016) 2852.
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This paper describes the fabrication of millimeter-long gold nanowires that bisect the center of microfluidic channels. We fabricated the nanowires by nanoskiving and then suspended them over a trench in a glass structure. The channel was sealed by bonding it to a complementary poly(dimethylsiloxane) structure. The resulting structures place the nanowires in the region of highest flow, as opposed to the walls where it approaches zero, and expose their entire surface area to fluid. We demonstrate active functionality, by constructing a hot-wire anemometer to measure flow through determining the change in resistance of the nanowire as a function of heat dissipation at low voltage (< 5V). Further, passive functionality is demonstrated by visualizing individual, fluorescently labelled DNA molecules attached to the wires. We measure rates of flow and show that, compared to surface-bound DNA strands, elongation saturates at lower rates of flow and background fluorescence from non-specific binding is reduced.

H. R. Zafarani, K. Mathwig, E. J. R. Sudhölter and L. Rassaei Electrochemical redox cycling in a new nanogap sensor: Design and simulation Journal of Electroanalytical Chemistry 760 (2016) 42.
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We propose a new geometry for nanogap electrochemical sensing devices. These devices consist of two closely spaced side-by-side electrodes which work under redox cycling conditions. Using finite element simulations, we investigate the effects of different geometric parameters on the redox cycling signal amplification to gain insight into the electrochemical sensing performance of the device design. This will allow optimizing the sensor performance of devices to be fabricated in the future.

S. Sarkar, A. F. Nieuwenhuis, S. Kang, K. Mathwig and S. G. Lemay
Integrated Microfluidics of Electrochemical Nanogap Sensors
Proceedings of the 19th International Conference on Miniaturized Systems for Chemistry and Life Science, Gyeongju, Korea, Oct. 25 – 29 (2015) 1522.
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K. Mathwig, Q. Chi, S. G. Lemay and L. Rassaei Handling and Sensing of Single Enzyme Molecules: From Fluorescence Detection Towards Nanoscale Electrical Measurements ChemPhysChem 17 (2015) 452.
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Classical methods to study single enzyme molecules have provided valuable information about distribution of conformational heterogeneities, reaction mechanisms, and transients in enzymatic reactions when individual molecules instead of an averaging ensemble are studied. Here, we highlight major advances in all-electrical single enzyme studies with a focus on recent micro- and nanofluidic tools which offer new ways of handling and studying small numbers of molecules or even single enzyme molecules. We particularly emphasize nanofluidic devices which enable the integration of electrochemical transduction and detection.

K. Mathwig, T. Albrecht, E. D. Goluch and L. Rassaei Challenges of Biomolecular Detection at the Nanoscale: Nanopores and Microelectrodes Analytical Chemistry 87 (2015) 5470.
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The interest in analytical devices, which typically rely on the reactivity of a biological component for specificity, is growing rapidly. In this Perspective, we highlight current challenges in all-electrical biosensing as these systems shrink towards the nanoscale and enable the detection of analytes at the single-molecule level. We focus on two sensing principles: nanopores and amperometric microelectrode devices.

K. J. Krause, K. Mathwig, B. Wolfrum and S. G. Lemay
Brownian motion in electrochemical nanodevices
The European Physical Journal Special Topics 223 (2014) 3156.
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Diffusion dominates mass transport in most electrochemical systems. In classical experimental systems on the micrometer scale or larger, this is adequately described at the mean-field level. However, nanoscale detection devices are being developed in which a handful or even single molecules can be detected. Brownian dynamics become manifest in these systems via the associated fluctuations in electrochemical signals. Here we describe the state of the art of these electrochemical nanodevices, paying particular attention to the role of Brownian dynamics and emphasizing areas in which theoretical understanding remains limited.

S. Sarkar, K. Mathwig, S. Kang, A. F. Nieuwenhuis and S. G. Lemay
Electrochemical Nanofluidic Assays in the Absence of Reference Electrode
Proceedings of the 18th International Conference on Miniaturized Systems for Chemistry and Life Science, San Antonio, USA, Oct. 26 – 30 (2014) 2122.
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Implementing a reliable reference electrode in miniaturized electrochemical sensors is challenging. Here, we present an alternative approach, based on redox cycling within a nanogap sensor consisting of two parallel electrodes, in which the reference electrode is omitted altogether. We show that on disconnection of the reference electrode, the solution potential floats to a certain value, which is explored theoretically and experimentally in order to quantitatively predict the potential. The obtained results are in good agreement with the theoretically reconstituted results.

S. Sarkar, K. Mathwig, S. Kang, A. F. Nieuwenhuis and S. G. Lemay
Redox Cycling Without Reference Electrode
Analyst 139 (2014) 6052.
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The reference electrode is a key component in electrochemical measurements, yet it remains a challenge to implement a reliable reference electrode in miniaturized electrochemical sensors. Here we explore experimentally and theoretically an alternative approach based on redox cycling which eliminates the reference electrode altogether. We show that shifts in the solution potential caused by the lack of reference can be understood quantitatively, and determine the requirements for accurate measurements in miniaturized systems in the absence of a reference electrode.

L. Rassaei, K. Mathwig, S. Kang, H. A. Heering and S. G. Lemay
Integrated Biodetection in a Nanofluidic Device
ACS Nano 8 (2014) 8278.
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The sensing of enzymatic processes in volumes at or below the scale of single cells is challenging but highly desirable in the study of biochemical processes. Here we demonstrate a nanofluidic device which combines an enzymatic recognition element and electrochemical signal transduction within a six femtoliter volume. Our approach is based on localized immobilization of the enzyme tyrosinase in a microfabricated nanogap electrochemical transducer. The enzymatic reaction product quinone is localized in the confined space of a nanochannel in which efficient redox cycling also takes place. Thus the sensor allows the sensitive detection of minute amounts of product molecules generated by the enzyme in real time. This method is ideally suited for the study of ultra-small volume systems such as the contents of individual biological cells or organelles.