Integrated Disposable Microfluidic Tissue Chips

Abstract

This thesis presents the design, implementation, and testing of a new platform for mimicking a wide range of physiological conditions using multi-layer thermoplastic microfluidic chips with integrated elastomeric membranes. The new platform is designed for high-throughput experiments, using disposable thermoplastic chips, and enabling precise control of channel pressures and flowrates. The platform can distribute up to 7 pneumatic signals to 4 microfluidic chips for control of high-throughput experiments in the incubator or on a microscope. The disposable chips are made entirely of Cyclic Olefin Copolymers (COC) and utilize on-chip pumps, pressure regulators, microfluidic accumulators, a novel hydrogel tissue compartment, and a standardized pneumatic interconnect. Channel flowrates are adjustable between 0-3 μL/s and pressures can be controlled up to 2 psi. The 5-layer chips are bonded together using a thin film COC elastomer membrane. The top and bottom layers are laminated using a co-extruded COC film with an easy-to-bond interface. Novel methods for reliable fabrication of these devices are explored, including laser machining of frozen membranes, and infrared bonding in a vacuum chamber. The chips are optically clear, exhibit strong thermal bonds, and display significantly lower levels of hormone absorption than earlier polydimethylsiloxane (PDMS) based devices. The design and analysis of the platform is described in detail, and the biological performance of the system is validated in studies promoting vasculogenesis in a co-culture of endothelial and stromal cells.