1024-Pixel CMOS Multimodality Joint Cellular Sensor/Stimulator Array for Real-Time Holistic Cellular Characterization and Cell-Based Drug Screening

This paper presents a fully integrated CMOS multimodality joint sensor/stimulator array with 1024 pixels for real-time holistic cellular characterization and drug screening. The proposed system consists of four pixel groups and four parallel signal-conditioning blocks. Every pixel group contains 16 x 16 pixels, and each pixel includes one 28 mu m x 28 mu m gold-plated electrode, four 12 mu m x 12 mu m photodiodes, and in-pixel circuits, within a 58 mu m x 58 mu m pixel footprint. Each pixel supports real-time extracellular potential recording, optical detection, charge-balanced biphasic current stimulation, and cellular impedance measurement for the same cellular sample. The proposed system is fabricated in a standard 130-nm CMOS process. Rat cardiomyocytes are successfully cultured on-chip. Measured high-resolution optical opacity images, extracellular potential recordings, biphasic current stimulations, and cellular impedance images demonstrate the unique advantages of the system for holistic cell characterization and drug screening. Furthermore, this paper demonstrates the use of optical detection on the on-chip cultured cardiomyocytes to real-time track their cyclic beating pattern and beating rate.