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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.