A 21952-Pixel Multi-Modal CMOS Cellular Sensor Array with 1568-Pixel Parallel Recording and 4-Point Impedance Sensing

This paper presents a fully integrated CMOS multi-modal cellular sensor/stimulator array with 21952 multi-modal pixels, 1568 simultaneous parallel readout channels, 16 μm×16 μm pixel pitch for single cell resolution, and 3.6 mm×1.6 mm tissue-level field-of-view (FoV), achieving high-resolution multi-parametric cellular potential/impedance/optical imaging for holistic cellular characterization and cell-based assays. Moreover, the array system reports the first on-chip true 4-point impedance sensing scheme with 16 parallel impedance sensing channels, which enables precise cellular impedance measurements with aggressively scaled electrodes and large electrode-electrolyte interfacial impedance. The chip also supports concurrent 16-channel 5-bit reconfigurable current-mode cell stimulation. The chip is implemented in a 130 nm low-cost standard CMOS process. Extracellular potentials (700 μV-1.5 mV) from on-chip cultured neonatal rat ventricular myocytes (NRVMs) are successfully measured. With on-chip cultured cardiac fibroblasts, full-chip high-resolution optical images and 4-point impedance mapping precisely capture cell distribution, growth, proliferation, and surface adhesion.