Understanding complex physiological processes requires the ability to monitor multiple biological modalities concurrently, as electrical, ionic, and biochemical processes are tightly coupled and cannot be holistically described by single-mode sensors. This article presents a 40 nm CMOS multimodal cellular physiology monitoring platform that integrates 40 960 reconfigurable pixels at

$10.8~\mu $

m pixel pitch. Each pixel supports electrophysiology recording, electrochemical sensing, ion-selective potentiometry, shadow imaging, and impedance spectroscopy, together with programmable voltage or current stimulation. Up to 10 240 pixels are recorded concurrently for extracellular potentials without direct pixel multiplexing, enabling a 23.6% effective sensing area and 25% peak simultaneous readout over a

$1.4\times 3.5$

mm² active field of view. For impedance sensing, a mixer-embedded delta–sigma modulator (ME-DSM) performs direct digitization, improving robustness to electrode offset and harmonic interference. The platform is validated with potassium-selective ion measurements, cyclic voltammetry of catecholamine-related neurotransmitters, and in vivo zebrafish cardiac potential recording, illustrating applicability from single cells to live small-animal models on-chip. We report a comprehensive and multimodal physiology-monitoring system.

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