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Electrochemical sensing arrays enable the spatial study of dopamine levels throughout brain slices, the diffusion of electroactive molecules, as well as neurotransmitter secretion from single cells. The integration of complementary metal-oxide semiconductor (CMOS) devices in the development of electrochemical sensing devices enables large-scale parallel recordings, providing beneficial high-throughput for drug screening studies, brain–machine interfaces, and single-cell electrophysiology. In this paper, an electrochemical sensor capable of recording at 40,000 frames per second using a CMOS sensor array with 1024 electrochemical detectors and a custom field-programmable gate array data acquisition system is detailed. A total of 1024 on-chip electrodes are monolithically integrated onto the designed CMOS chip through post-CMOS fabrication. Each electrode is paired with a dedicated transimpedance amplifier, providing 1024 parallel electrochemical sensors for high-throughput studies. To support the level of data generated by the electrochemical device, a powerful data acquisition system is designed to operate the sensor array as well as digitize and transmit the output of the CMOS chip. Using the presented electrochemical sensing system, both dopamine and hydrogen peroxide diffusions across the sensor array are successfully recorded at 40,000 frames per second across the 32 × 32 electrochemical detector array. 

This study aims to develop a microelectrode array-based neural probe that can record dopamine activity with high stability and sensitivity. To mimic the high stability of the gold standard method (carbon fiber electrodes), the microfabricated platinum microelectrode is coated with carbon-based nanomaterials. Carboxyl-functionalized multi-walled carbon nanotubes (COOH-MWCNTs) and carbon quantum dots (CQDs) were selected for this purpose, while a conductive polymer like poly (3-4-ethylene dioxythiophene) (PEDOT) or polypyrrole (PPy) serves as a stable interface between the platinum of the electrode and the carbon-based nanomaterials through a co-electrodeposition process. Based on our comparison between different conducting polymers and the addition of CQD, the CNT–CQD–PPy modified microelectrode outperforms its counterparts: CNT–CQD–PEDOT, CNT–PPy, CNT–PEDOT, and bare Pt microelectrode. The CNT–CQD–PPy modified microelectrode has a higher conductivity, stability, and sensitivity while achieving a remarkable limit of detection (LOD) of 35.20 ± 0.77 nM. Using fast-scan cyclic voltammetry (FSCV), these modified electrodes successfully measured dopamine’s redox peaks while exhibiting consistent and reliable responses over extensive use. This electrode modification not only paves the way for real-time, precise dopamine sensing using microfabricated electrodes but also offers a novel electrochemical sensor for in vivo studies of neural network dynamics and neurological disorders. 

In the study of the brain, large and high-density microelectrode arrays have been widely used to study the behavior of neurotransmission. CMOS technology has facilitated these devices by enabling the integration of high-performance amplifiers directly on-chip. Usually, these large arrays measure only the voltage spikes resulting from action potentials traveling along firing neuronal cells. However, at synapses, communication between neurons occurs by the release of neurotransmitters, which cannot be measured on typical CMOS electrophysiology devices. Development of electrochemical amplifiers has resulted in the measurement of neurotransmitter exocytosis down to the level of a single vesicle. To effectively monitor the complete picture of neurotransmission, measurement of both action potentials and neurotransmitter activity is needed. Current efforts have not resulted in a device that is capable of the simultaneous measurement of action potential and neurotransmitter release at the same spatiotemporal resolution needed for a comprehensive study of neurotransmission. In this paper, we present a true dual-mode CMOS device that fully integrates 256-ch electrophysiology amplifiers and 256-ch electrochemical amplifiers, along with an on-chip 512 electrode microelectrode array capable of simultaneous measurement from all 512 channels.