High-Frequency Nanocapacitor Arrays: Concept, Recent Developments, and Outlook

Abstract

We have developed a measurement platform for performing high-frequency AC detection at nanoelectrodes. The system consists of 65 536 electrodes (diameter 180 nm) arranged in a sub-micrometer rectangular array. The electrodes are actuated at frequencies up to 50 MHz, and the resulting AC current response at each separately addressable electrode is measured in real time. These capabilities are made possible by fabricating the electrodes on a complementary metal-oxide-semiconductor (CMOS) chip together with the associated control and readout electronics, thus minimizing parasitic capacitance and maximizing the signal-to-noise ratio. This combination of features offers several advantages for a broad range of experiments. First, in contrast to alternative CMOS-based electrical systems based on field-effect detection, high-frequency operation is sensitive beyond the electrical double layer and can probe entities at a range of micrometers in electrolytes with high ionic strength such as water at physiological salt concentrations. Far from being limited to single- or few-channel recordings like conventional electrochemical impedance spectroscopy, the massively parallel design of the array permits electrically imaging micrometer-scale entities with each electrode serving as a separate pixel. This allows observation of complex kinetics in heterogeneous environments, for example, the motion of living cells on the surface of the array. This imaging aspect is further strengthened by the ability to distinguish between analyte species based on the sign and magnitude of their AC response. Finally, we show here that sensitivity down to the attofarad level combined with the small electrode size permits detection of individual 28 nm diameter particles as they land on the sensor surface. Interestingly, using finite-element methods, it is also possible to calculate accurately the full three-dimensional electric field and current distributions during operation at the level of the Poisson-Nernst-Planck formalism. This makes it possible to validate the interpretation of measurements and to optimize the design of future experiments. Indeed, the complex frequency and spatial dependence of the data suggests that experiments to date have only scratched the surface of the method's capabilities. Future iterations of the hardware will take advantage of the higher frequencies, higher electrode packing densities and smaller electrode sizes made available by continuing advances in CMOS manufacturing. Combined with targeted immobilization of targets at the electrodes, we anticipate that it will soon be possible to realize complex biosensors based on spatial- and time-resolved nanoscale impedance detection.

Individual Detection and Characterization of Non‐Electrocatalytic, Redox‐Inactive Particles in Solution by using Electrochemistry

“…[85,87,90] (1) The experimental capacitive impacts reported are unidirectional at a given applied potential, which may call into question the ability (time response) of the instrumentation to record all the 'history' of the event, which could imply bidirectional spikes under certain conditions. 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 fields, [16,32,33] arrays of UMEs, [34][35][36][37] as well as combined strategies [31,36] through which sub-aM concentrations have been reached. [31]…”

“…Nevertheless, given that the charge involved is generally very small, the detection of nanoparticles is particularly challenging and particles of micrometric size (at least in one dimension), which can affect relatively 'large' areas of the EDL, have been mostly reported. An exception worth noting is the line under development by Lemay and co-workers [37] through which the detection of individual landing nanoparticles has been achieved by record -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 ing changes in capacitance with time of sensors surfaces composed of thousands of nanoelectrodes of highly-reduced parasitic noise.…”

A CMOS Pixelated Nanocapacitor Biosensor Platform for High-Frequency Impedance Spectroscopy and Imaging

“…LECTROCHEMICAL impedance spectroscopy (EIS) is a popular sensing technique, thanks to its capability to investigate different sample properties at different frequencies [1]. Miniaturization and monolithic integration of EIS sensors in CMOS technology is possible, enabling highly parallel sensing and readout [2] [13].…”

Nanoscale Electrochemical Sensing and Processing in Microreactors

“…With ever-decreasing pixel size in CMOS technology, this could be a potentially powerful technique to detect items with submicrometer dimensions, such as nanoparticles, viruses, or even proteins. With further downscaling, the operating frequency could theoretically be increased beyond the dielectric relaxation cut-off frequency of the electrolyte, effectively eliminating the dependence on ionic conductivity (48).…”