A CMOS IC-based multisite measuring system for stimulation and recording in neural preparations in vitro

Abstract

In this report, we describe the system integration of a complementary metal oxide semiconductor (CMOS) integrated circuit (IC) chip, capable of both stimulation and recording of neurons or neural tissues, to investigate electrical signal propagation within cellular networks in vitro. The overall system consisted of three major subunits: a 5.0 × 5.0 mm CMOS IC chip, a reconfigurable logic device (field-programmable gate array, FPGA), and a PC. To test the system, microelectrode arrays (MEAs) were used to extracellularly measure the activity of cultured rat cortical neurons and mouse cortical slices. The MEA had 64 bidirectional (stimulation and recording) electrodes. In addition, the CMOS IC chip was equipped with dedicated analog filters, amplification stages, and a stimulation buffer. Signals from the electrodes were sampled at 15.6 kHz with 16-bit resolution. The measured input-referred circuitry noise was 10.1 μ V root mean square (10 Hz to 100 kHz), which allowed reliable detection of neural signals ranging from several millivolts down to approximately 33 μ Vpp. Experiments were performed involving the stimulation of neurons with several spatiotemporal patterns and the recording of the triggered activity. An advantage over current MEAs, as demonstrated by our experiments, includes the ability to stimulate (voltage stimulation, 5-bit resolution) spatiotemporal patterns in arbitrary subsets of electrodes. Furthermore, the fast stimulation reset mechanism allowed us to record neuronal signals from a stimulating electrode around 3 ms after stimulation. We demonstrate that the system can be directly applied to, for example, auditory neural prostheses in conjunction with an acoustic sensor and a sound processing system.

Revealing neuronal function through microelectrode array recordings

“…Jimbo et al proposed a method to decouple the recording amplifiers during stimulation, sample the electrode potential during recording and add the stimulation pulse to the stored electrode potential (Jimbo et al, 2003 ). This scheme has also been implemented on dedicated ASICs to be used in conjunction with MEA devices (Brown et al, 2008 ; Hottowy et al, 2012 ; Tateno and Nishikawa, 2014 ). Figures 4E,F show stimuli activated neuronal responses with high spatiotemporal precision.…”

Developing a Frequency‐selective Piezoelectric Acoustic Sensor Sensitive to the Audible Frequency Range of Rodents

“…In such stimulation systems, the amplified signals from the multiple channels in the PAT are converted into DC voltage signals using a rectifier circuit; these signals are then used as reference voltages to determine the magnitudes of the signals required to stimulate the auditory neurons at multi-sites. For example, a logic circuit with a clock pulse generator can be used to control both the stimulation waveform and the driving period of the stimulation [21]. Using such logic circuits, the amplitude and the frequency of the stimulation waveform are modulated in a manner that is dependent on the amplitude of the reference voltage, which is a function of the applied sound pressure.…”

Emerging Three‐Dimensional Integrated Systems for Biomimetic Neural In Vitro Cultures

“…[106] Moreover, the use of complementary metal oxide semiconductor (CMOS) MEAs offer the capability to investigate the propagation of electrical signal at high density in vitro. [230] Novel 3D MEAs encapsulated in hydrogels, such as a polysaccharide-based hydrogel interfaced with conductive pillars, or low-cost 3D printed MEAs, have been also proposed. [231,232] The various 3D in vitro technological-and cell-driven neural models discussed in this section have been classified in Table 2 with respect to the main production technologies and materials.…”