Circuits and Systems for Nanoelectrode Array Biosensors
High-frequency impedance spectroscopy nanobiosensors have been used to detect and characterize a variety of analytes in electrolyte (e.g., microbeads, cells, viruses, proteins). Thanks to their small size (comparable to the size of the target biomolecules), nanoscale sensors allow to perform single-particle detection. This is especially enabled by CMOS integration and scaling. Furthermore, massively parallel nanoelectrode array implementations (see figure) are well suited for achieving high spatial resolutions, possibly surpassing the resolution of conventional optical systems. However, in order to overcome the screening of the signals caused by the electrical double layer (ions accumulating on the electrode's surface), high-frequencies of operation are required [1-3].
Charge-based capacitance measurements (CBCM) are a popular sensing approach to achieve high frequencies of operation with a compact implementation. In a nutshell, the principle of operation consists in alternatively charging/discharging a nanoelectrode with two switches; by integrating the resulting average charging current, the transferred charge (and ultimately the capacitance at the nanoelectrode) can be estimated.
Within this framework, we consider the novel CMOS biochip described in [1-3], originally developed by NXP Semiconductors. At DIEF (University of Modena and Reggio Emilia) an experimental high-frequency impedance spectroscopy CMOS platform is available for experimentation in dry and liquid environments with the above biochips. In parallel, IIS at ETHZ (http://www.iis.ee.ethz.ch/) is currently developing the next generation of high-speed control boards used to actuate the CBCM cells of the biochips.
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The references can be accessed free of charge within the ETHZ network.
 F. Widdershoven et al.: A CMOS Pixelated Nanocapacitor Biosensor Platform for High-Frequency Impedance Spectroscopy and Imaging
 S. G. Lemay et al.: High-Frequency Nanocapacitor Arrays: Concept, Recent Developments, and Outlook
 C. Laborde et al.: Real-time imaging of microparticles and living cells with CMOS nanocapacitor arrays