Microfluidic Platform for Vascularized Tissue Models

Abstract

This thesis presents a microfluidic platform designed to support 3D vascularized tis­sue models for microphysiological systems. The platform delivers pneumatic pressure and vacuum signals to drive fluid flow and pressure on tissue culture devices with integrated pumps and back-pressure regulators. The mechanical performance of the pumps and back-pressure regulators is characterized. Tissue compartments in each device contain endothelial and stromal cells suspended in a hydrogel during culture. An oxygenating reservoir stores and replenishes oxygen in circulating cell culture me­dia. During assembly, screws are used to compress an elastomeric membrane, forming a seal and transmitting pneumatic pressure signals from the connection manifold to acutate the fluidic control elements. After a biological experiment the tissue culture devices can be disassembled, cleaned, and re-used, thus enabling cost-effective experi­mentation and prototyping. Each of the 4 layers of the tissue culture devices arc ma.de of thermoplastic polymers, and their design is translatable to injection molding for future production at scale. The design and manufacturing methods for the platform and individual device features are discussed. Two major biological experiments are presented to demonstrate the platform's ability to support emergent vascularization in the tissue culture device over 7 days. Microscope images show development of perfusable microvessel networks.