The Development of Biomicrofluidics by Resin 3D Printing for Immunological Analysis

Bioanalytical microfluidic devices allow researchers to deeply analyze biological samples by providing fine control over essential microenvironment properties. Recently, such devices have been used for applications ranging from clinical diagnostics to organ-level immunological research. However, typical microfluidic customization and fabrication can be difficult to access, especially for those not equipped with common microfabrication facilities (i.e., clean rooms). Furthermore, many commercial microfabrication materials are not innately biocompatible. To address these limitations, this work focuses on the fabrication and design of user-friendly microfluidic devices, tested for function and compatibility with sensitive immunological cell and tissue cultures. To streamline microfluidic development, we outlined an optimized workflow for cutting-edge resin polymerization 3D printing to produce customizable biomicrofluidics with commercially available materials. With this work, we demonstrate methods to increase print resolution, address optical properties of common resin materials, and increase biocompatibility and reusability of prints using surface treatments with parylene-C. To further simplify microfluidic setup and mitigate air-driven flow perturbances, we also developed printable designs allowing for 1) conformal connections between rigid, resin-printed chips to soft pump tubing and 2) bubble trapping for keeping gas disruptions from the line of flow. These methods were then applied to the construction of biomicrofluidics for use with live, immune cell and tissue cultures; including a tissue perfusion chip intended to enhance tissue cultures by applying consistent, trans-perfusion of media. Overall, this work provides new tools and fluidic setups using optimized 3D printing fabrication to increase microfluidic accessibility for bioanalytical researchers, thus expediting progress to answer biologically relevant questions.