Provided herein is a microphysiological system that may be used in various cell culture applications and biological system studies, that facilitates co-culture, monitoring, and study of functional interactions among different types of cellular and biological materials under various environmental conditions. The system is configured for fast assembly and disassembly, thereby minimizing damage or contamination of the biological materials and environmental conditions inside the system. The system comprises a base, a lid, and a plurality of clamps that are connected to the base and the lid. The base has a recess surface for receiving cell culture support layers. The lid has a stepped surface configured to exert a contact force to a top layer of one or more cell culture support layers during use. The clamp involves an engagement mechanism that generates a contact force allowing for sealing of the cell culture support layers in a manner that minimizes leakage of fluids.