Design, fabrication, and reduction to practice of milliscale membrane-free organ chip systems
The goal of this research was to establish a novel digital manufacturing-based workflow for the fabrication of membrane free organ chip (MFOC) systems. This workflow is based on the implementation of top-down design, starting with CAD design of molds for MFOC components and can be conducted on a benchtop removing the need for cleanroom use. In conducting this research, a commercially available SLA printer was characterized and optimized for manufacturing molds suitable for MFOC fabrication. To achieve this, extensive research was required to determine printer resolution limits and work within the limitations of the resins available for printing. Specifically, the molds need to be flat and smooth in order to produce perfectly horizontal and transparent PDMS devices. Post-processing workflows were engineered to satisfy these MFOC design constraints. After establishing a reliable and reproducible workflow for MFOC fabrication, the focus of the research was reduction to practice, i.e. achieving a design that enables loading MFOC with patterned aqueous solutions with 100% success and a high degree of forgiveness. Key MFOC dimensions were systematically varied in a manner only possible with the rapid prototyping capability of DM in a series of experiments with a standardized injection test and success rate of loading as the primary output. With a robust MFOC design in place, more complex designs for tissue patterning applications were created, and advanced configurations for engineering patterned vascularized stromal tissues were tested and validated. Seqeuntial and simultaneous loading scenerios were imvestigated to better understand cell migration impedence in multi-gel lane devices.