Search for: All records

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. 

Dopamine constitutes a significant portion of the catecholamine content in the brain and plays a distinct role in neuromodulation including directing motor control, motivation, reward, and cognitive function. For future neuroprobe technology, not only is simultaneous high-density neurochemical recording vital, temporal resolution plays a key part in the roles of the spatiotemporal distributions of catecholamines in the brain. In this work, we present a new probe design that contains a 256 microelectrode array with an integrated 256 transimpedance amplifier array capable of both amperometry and fast-scan cyclic voltammetry. Each amplifier in the array is capable of both modes of electrochemical detection with three gain settings for the voltammetry mode and occupies an area of 60 μm × 60 μm. The new probe enables a high-resolution spatiotemporal mapping of neurochemicals in the brain. 

The electrical potential recordings using a large microelectrode array from neuronal cultures has been widely used to monitor neural spike activities and cellular activities. However, this approach does not monitor neurochemical release, and therefore only contains indirect information regarding synaptic neurotransmission. At the synapses, these action potentials instigate the secretion of neurotransmitters. Neurochemical recordings, based on electrochemical methods, enable the direct monitoring of synaptic transmissions with single-vesicle resolution as well as the excellent temporal resolution in the microsecond scale. The neural spike activities and the neurotransmitter secretions are related; however, one cannot be used to predict the other because of the complex vesicle trafficking and exocytosis processes. Here, we present a dual-mode amplifier array which integrates 256-ch transconductance amplifiers and 256-ch transimpedance amplifiers. The dual-mode amplifier array enables the simultaneous recordings of electrophysiology and neurochemical activities. Capturing both neurochemical and neural spike (action potential and local field potential) activities would provide comprehensive spatiotemporal images of the brain activities. 

Abstract Neuronal exocytosis facilitates the propagation of information through the nervous system pertaining to bodily function, memory, and emotions. Using amperometry, the sub-millisecond dynamics of exocytosis can be monitored and the modulation of exocytosis due to drug treatment or neurodegenerative diseases can be studied. Traditional single-cell amperometry is a powerful technique for studying the molecular mechanisms of exocytosis, but it is both costly and labor-intensive to accumulate statistically significant data. To surmount these limitations, we have developed a silicon-based electrode array with 1024 on-chip electrodes that measures oxidative signal in 0.1 millisecond intervals. Using the developed device, we are able to capture the modulation of exocytosis due to Parkinson’s disease treatment (L-Dopa), with statistical significance, within 30 total minutes of recording. The validation study proves our device’s capability to accelerate the study of many pharmaceutical treatments for various neurodegenerative disorders that affect neurotransmitter secretion to a matter of minutes. 

A common problem in single-cell measurement is the low-throughput nature of measurements. Monolithic CMOS microsystems have enabled many parallel measurements to take place simultaneously to increase throughput due to the integration of electrodes and amplifiers into a single chip. This paper explores a CMOS chip containing an array of 1024 parallel transimpedance amplifiers that takes advantage of a “half-shared” operational amplifier architecture. This architecture splits a traditional 5-transistor operational amplifier into two, the inverting half and the non-inverting half. Splitting an amplifier into two allows for the non-inverting half to be “shared” with several inverting halves, reducing the die area required for each individual amplifier. This allows for an increased number of amplifiers to be embedded into the same chip; in this case, 32 amplifiers are able to fit in the same space as 17 traditional 5-transistor operational amplifiers. The amplifiers exhibit low mismatch of 1.65 mV across the entire 1024 amplifier array, as well as high linearity in transimpedance gain. The technique will enable larger arrays to be created in future designs to allow electrophysiologists, among others, access to even higher-throughput measurement tools.