The development of a 3D-printed multi-tissue chip and tubing-free impeller pump to model communication with the lymph node

Multi-organs-on-chip (MOOC) technology provides a method to model inter-organ communication. These devices fluidically connect two or more tissue models within a microfluidic chip to enable molecular cross-talk. However, there is an unmet need within the field to build immune-competent MOOCs and, in particular, include immune organs such as the lymph node (LN). This dissertation describes the development of a 3D-printed multi-tissue chip and tubing-free impeller pump to model communication with the LN in the context of inflammation and disease (Figure 1). Chapter 2 explores the development of the impeller pump, a novel pumping system that generated recirculating fluid flow without the use of tubing. Chapter 3 focuses on the optimization of resin composition and post-treatment to improve biocompatibility with sensitive immune cells. In Chapter 4, a 3D-printed multi-tissue chip for murine LN slice culture and a companion motor-based impeller pump was established and used to model a vaccine injection in the skin draining to a local lymph node. Chapter 5 describes a 3D-printed multi-media multi-tissue chip designed to support human 2D and 3D cell culture models in commercially available transwells to model brain-immune interactions in the context of neuroinflammation and neurodegeneration. In the future, the impeller pump and multi-tissue chip described here can be used to model complex phenomena such as neurodegeneration, autoimmunity, tumor immunity, and vaccination.