This thesis presents multimodality CMOS sensor and stimulator array for holistic cellular characterization and cell-based drug screening. Cells are the basic structural, functional, and biological units of all known living organisms. Understanding the physiological behaviors of living cells and tissues is a prerequisite to further advance bioscience and biotechnologies. However, cells are highly complex systems often with concurrent multi-physics responses when subjected to external stimuli, which cannot be captured by conventional single-modality sensors, e.g., with electrical or optical only detection. Furthermore, cell signals are often encoded by spatiotemporal dynamics and coupled by multiple cellular activities. Thus, there is an unmet need for new multi-modality sensor arrays comprised of pixels each capable of detecting multi-physics cellular responses together with actuations. In this thesis, we demonstrate a fully integrated multimodality sensor and stimulator array in a standard CMOS process. The CMOS-based fully integrated cellular interfacing array can measure four different cell physiological parameters, i.e., extracellular potential recording, cellular impedance mapping, optical shadow imaging/bioluminescence imaging, and temperature monitoring in a real-time joint-modality fashion together with biphasic current stimulation on the same cellular sample. Electrical measurements and extensive on-chip cultured cell-based experiments are performed to demonstrate the functionalities of the proposed multi-modality chip in holistic cell characterization and drug screening.
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A multimodality CMOS cellular interfacing array for holistic cellular characterization and cell-based drug screening
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