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This lecture delves into the utilization of CMOS technology to establish direct interfaces with living systems, exploring the challenges and advantages of moving beyond traditional optical methods. The instructor discusses the potential of CMOS integration in enabling high-fidelity measurements, multiplexing capabilities, and direct electrical interactions with biological components, such as single molecules, ion channels, and bacterial colonies. Various applications are explored, including single molecule bioelectronics, electrochemical imaging for studying bacterial infections, and the development of hybrid systems combining biological and solid-state components. The lecture also covers the design of flexible CMOS electronics for neural interfaces, aiming to bridge the gap between micro and macro-level understanding of brain function.