Rapidly prototyping complex microfluidics through stereolithography

Abstract

As organ-on-a-chip research becomes more popular, greater effort is being placed into creating in vitro cell culture systems that more accurately represent the complexity of in vivo biology. Microfluidics, or the manipulation and analysis of microliter-scale fluids in micro-channels and chambers, have enabled the creation of increasingly complex 3D cell culture platforms that can better represent organ-level functionality. For decades, micromolded polydimethylsiloxane (PDMS) has been the predominant microfluidics prototyping tool because of its high-resolution patterning, biocompatibility, and optical transparency. However, the disadvantages associated with its manufacturability, and thus its rapid prototypability, limits the prospect of using PDMS for future organ-on-a-chip systems. This work aims to demonstrate the advantages of digital manufacturing and stereolithography for the production, testing, and development of complex microfluidic devices. Through the addition of novel monomers to stereolithography resin formulations, I proved that the functionalization of 3D printable hard plastic was possible with essentially any biomolecule of interest. These materials can then be used to produce high resolution structures in all three spatial dimensions, enabling the fabrication of unique structures that can only be fabricated through stereolithography. A hard plastic muscle cell-in-gel culture system was developed for long-term culture, differentiation, and fusion of myocytes into myotubes. Then, a finite element analysis program was used to prototype a microfluidic device capable of producing complex, 3D gradients within short timescales; the device was tested using colorimetric reagents. Lastly, a microfluidic microneedle array was tested to help improve the efficacy of induced pluripotent stem cell delivery during intramyocardial injection of infarcted heart tissues. By proving stereolithography is a valuable tool for microfluidic device fabrication, testing, and rapid prototyping, I aim to increase its implementation and dissemination as a means of experimenting with more biologically representative in vitro models.