One of the most challenging, yet highly rewarding tasks in biological research is to visualize with high spatial resolution the structure of molecula machines and their interactions in cellular function under physiological conditions, such as in 37 ?C aqueous environment. This proposed LiquidCell EM system with precise temperature control enables direct imaging of many dynamic biological processes in truly native environments with ultra high resolution using transmission electron microscopy. In this proposal, we will fabricate the self-contained liquid cells with ultra-thin viewing windows. Precise temperature control of 37+/-0.1 ?C will be achieved through microfluidic device fabrication. Test experiments of imaging individual proteins, protein assembly and live cell functions will be performed to optimize the system for in vivo biological imaging under physiological conditions.