Date of Award
Master of Science (MS)
The advent of Tissue-on-a-Chip (TiOC) devices has provided a novel way for researchers to approach biological study and drug development. As a platform that enables human in vivo conditions to be accurately replicated ex vivo, TiOC can accelerate both fundamental biological research to answer basic questions regarding tissue behavior and function (e.g., cell-cell interactions in the tumor microenvironment (TME)) and translational research that includes testing of standard and novel therapeutics. The reported work focuses on development of processes and technologies common to two classes of TiOC. The first device is a single-layer, multi-compartment microfluidic device for investigation of pancreatic ductal adenocarcinoma (PDAC) tumor behavior in a comprehensive TME that includes cancer and non-cancer cell types. The second is a multi-layer, multi-compartment (chamber-over-chamber) device for human gut research. Both systems are designed to support a perfused vascular network in communication with the tissue of interest (tumor or gut epithelial cells). It was found that the devices can be made by utilizing conventional microfabrication methods and can be constructed in such a way that experiments are repeatable and customizable for different cell types and environmental conditions. One-step soft lithography and a straightforward assembly process were used to mold the single-layer elastomeric (polydimethylsiloxane, PDMS) Tumor-on-a-Chip (TOC). Soft lithography was also used to mold components (two channels and a porous PDMS membrane) of the Gut-on-a-Chip (GOC); however, the small size of the mold pillars, corresponding to pores of the PDMS membrane, necessitated a more sophisticated fabrication approach. Further, the chamber-over-chamber design of the GOC required development of an alignment jig for device assembly. Challenges, pitfalls, and successes are discussed.
Dr. John Mark Meacham
Dr. Misty Good Dr. Jessica Wagenseil