Parallel 1024-ch Cyclic Voltammetry on Monolithic CMOS Electrochemical Detector Array

Large-scale microelectrode arrays offers enhanced spatiotemporal resolution in electrophysiology studies. In this paper, we discuss the design and performance of an electrochemical detector array which is capable of 1024-ch parallel cyclic voltammetry. The electrochemical detector is fabricated using a custom-designed CMOS chip, which integrates both the circuity and on-chip microelectrode array, to operate the array and record electrochemical signals. For parallel 1024-ch recordings, 1024 capacitor-based integrating transimpedance amplifiers are designed. The amplifier design features bipolar capabilities for measuring both negative and positive electrochemical currents due to reduction and oxidation reactions. The cyclic voltammetry functionality was validated by measuring the double-layer capacitance of the on-chip electrode array. Cyclic voltammetry can be used to examine the quality of electrochemical electrodes by measuring the double-layer capacitance that forms at the electrode-electrolyte interface. Double-layer capacitance is a function of the effective area of the electrode. A contaminated electrode can have smaller effective area resulting in smaller double-layer capacitance. Using the parallel cyclic voltammetry capability of the monolithic CMOS device, the double layer capacitance of all 1024 electrodes can be simultaneously measured to examine the status of the electrode array in real time. The initial measurement of the electrode array showed a mean capacitance of 0.47 nF. After plasma treatment to remove contamination on the electrode's surface, the increased capacitance was 1.36 nF nearly tripling the effective surface area. This method can accelerate the characterization of an electrode array before analytical experiments to provide well-controlled electrochemical electrodes, which are crucial in conducting reliable electrochemical measurements.

I. Introduction

Large-scale microelectrode arrays (MEA) offer high spatiotemporal resolution for electrophysiology studies. MEAs have been useful in enhancing the spatial resolution of electrochemical recordings, such as mapping the level of H₂O₂ in relation to neurological diseases in a brain slice [1], electrochemical imaging of redox molecules diffusing across an MEA [2], and imaging of metabolites in biofilms [3]. Large-scale MEA is especially useful in single-cell electrophysiology in which a large number of simultaneous recordings take place in order to account for heterogeneity in the characteristics of quantal release among the cell population [4]. For these reasons, high-throughput simultaneous measurements from a large number of cells would result in a tremendous benefit in enabling rapid studies of neurodegenerative disorders, the effects of therapies as well as new drug discoveries that target neurotransmitter release. Significant cost reduction in the single-cell electrophysiological analysis will also allow the evaluation of emerging treatments for side effects on molecular and cellular levels before it is clinically used.