A novel 16k micro-nail CMOS-chip for in-vitro single-cell recording, stimulation and impedance measurements

In neurophysiological and pharmaceutical research, parallel and individual access to a dense population of in-vitro cultured neurons is a key feature for analyzing networks of neurons. This paper presents a 0.18μm CMOS chip containing a dense array of micro-nail electrodes, a 128 × 128 sensor/actuator matrix with in-situ differential amplification circuits, pico-Ampere current stimulation, and impedance measurement circuits. Measurements on packaged chips show successful impedance measurements matching the simulation model and electrical recordings of in-vitro cultured cardiomyocytes, correlated with recorded changes in intra-cellular calcium concentrations. This system is a first step towards a high-throughput neuron/chip interface.