Described herein are environmentally isolated tissue culture devices that may be used for cell culture, as well as systems including these devices and methods for using them. These devices may include control features for regulating the micro-environment within a well or wells of the device. For example, on-board features may regulate the temperature, humidity, pH, media level, media composition, CO2/O2/N2 levels, drug concentration, cell density, byproduct (or product) production, and mixing of materials within the chamber. Material may be added to or withdrawn from the wells of the device without opening the device. Also described herein are controllers for analyzing and controlling the micro- environment within the well. Thus, the plates described herein may be used without requiring a separate incubator, allowing cells to be analyzed (e.g., imaged) continuously, allowing real-time reactions while monitoring under a microscope for hours, days or even weeks.