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© 2021 The Authors. Published by American Chemical Society.Complementary metal–oxide–semiconductor (CMOS) microelectrode arrays integrate amplifier arrays with on–chip electrodes, offering high–throughput platforms for electrochemical sensing with high spatial and temporal resolution. Such devices have been developed for highly parallel constant voltage amperometric detection of transmitter release from multiple cells with single–vesicle resolution. Cyclic voltammetry (CV) is an electrochemical method that applies voltage waveforms, which provides additional information about electrode properties and about the nature of analytes. A 16–channel, 64–electrode–per–channel CMOS integrated circuit (IC) fabricated in a 0.5 μm CMOS process for CV is demonstrated. Each detector consists of only 11 transistors and an integration capacitor with a unit dimension of 0.0015 mm2. The device was postfabricated using Pt as the working electrode material with a shifted electrode design, which makes it possible to redefine the size and the location of working electrodes. The system incorporating cell–sized (8 μm radius) microelectrodes was validated with dopamine injection tests and CV measurements of potassium ferricyanide at a 1 V/s scanning rate. The cyclic voltammograms were in excellent agreement with theoretical predictions. The technology enables rigorous characterization of electrode performance for the application of CMOS microelectrode arrays in low–noise amperometric measurements of quantal transmitter release as well as other biosensing applications.