Low-Power Fully Integrated 256-Channel Nanowire Electrode-on-Chip Neural Interface for Intracellular Electrophysiology

Intracellular electrophysiology, a vital and versatile technique in cellular neuroscience, is typically conducted using the patch-clamp method. Despite its effectiveness, this method poses challenges due to its complexity and low throughput. The pursuit of multi-channel parallel neural intracellular recording has been a long-standing goal, yet achieving reliable and consistent scaling has been elusive because of several technological barriers. In this work, we introduce a micropower integrated circuit, optimized for scalable, high-throughput in vitro intrinsically intracellular electrophysiology. This system is capable of simultaneous recording and stimulation, implementing all essential functions such as signal amplification, acquisition, and control, with a direct interface to electrodes integrated on the chip. The electrophysiology system-on-chip (eSoC), fabricated in 180nm CMOS, measures 2.236 mm $\times$ 2.236 mm. It contains four 8 $\times$ 8 arrays of nanowire electrodes, each with a 50 $\mu$m pitch, placed over the top-metal layer on the chip surface, totaling 256 channels. Each channel has a power consumption of 0.47 $\mu$W, suitable for current stimulation and voltage recording, and covers 80 dB adjustable range at a sampling rate of 25 kHz. Experimental recordings with the eSoC from cultured neurons in vitro validate its functionality in accurately resolving chemically induced multi-unit intracellular electrical activity.