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We present novel voltage stimulation buffers with controlled output current, along with recording circuits featuring adjustable high-pass cut-off filtering to perform efficient stimulation while actively suppressing stimulation artifacts in high-density microelectrode arrays. Owing to the dense packing and close proximity of the electrodes in such systems, a stimulation through one electrode can cause large electrical artifacts on neighboring electrodes that easily saturate the corresponding recording amplifiers. To suppress such artifacts, the high-pass corner frequencies of all available 2048 recording channels can be raised from several Hz to several kHz by applying a “soft-reset” or pole-shifting technique. With the implemented artifact suppression technique, the saturation time of the recording circuits, connected to electrodes in immediate vicinity to the stimulation site, could be reduced to less than 150 μs. For the stimulation buffer, we developed a circuit, which can operate in two modes: either control of only the stimulation voltage or control of current and voltage during stimulation. The voltage-only controlled mode employs a local common-mode feedback operational transconductance amplifier with a near rail-to-rail input/output range, suitable for driving high-capacitive loads. The current/voltage controlled mode is based on a positive current conveyor generating adjustable output currents, whereas its upper and lower output voltages are limited by two feedback loops. The current/voltage controlled circuit can generate stimulation pulses up to 30 μA with less than ±0.1% linearity error in the low-current mode and up to 300 μA with less than ±0.2% linearity error in the high-current mode. [ABSTRACT FROM AUTHOR]

Biological cells are characterized by highly complex phenomena and processes that are, to a great extent, interdependent. To gain detailed insights, devices designed to study cellular phenomena need to enable tracking and manipulation of multiple cell parameters in parallel; they have to provide high signal quality and high-spatiotemporal resolution. To this end, we have developed a CMOS-based microelectrode array system for in vitro applications that integrates six measurement and stimulation functions, the largest number to date. Moreover, the system features the largest active electrode array area to date ( $4.48 \times 2.43$ mm2) to accommodate 59 760 electrodes, while its power consumption, noise characteristics, and spatial resolution (13.5- $\mu$ m electrode pitch) are comparable to the best state-of-the-art devices. The system includes: 2048 action potential (AP, bandwidth: 300 Hz–10 kHz) recording units, 32 local-field-potential (LFP, bandwidth: 1 Hz–300 Hz) recording units, 32 current recording units, 32 impedance measurement units, and 28 neurotransmitter detection units, in addition to the 16 dual-mode voltage-only or current/voltage-controlled stimulation units. The electrode array architecture is based on a switch matrix, which allows for connecting any measurement/stimulation unit to any electrode in the array and for performing different measurement/stimulation functions in parallel. [ABSTRACT FROM PUBLISHER]