The design and characterization of a next generation microfluidic device for in vitro modeling of bilayer tissue constructs
Spencer, Abigail June
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Advanced tissue culture platforms harness microfabrication techniques and properties of biocompatible materials to create tunable and physiologically-relevant microenvironments. Traditional in vitro tissue models are restricted to flat, static culture plates, which allow for high-throughput experimentation but do not support physiological tissue function. Early research investigates cell response to physiological mechanical cues[1–3], but these devices are largely confined to materials like PDMS or have too low throughput for industry use. The next generation of platforms will combine mechanical cues and integrated sensing with materials that are biologically inert and compatible with high throughput assays and large scale manufacturing, while remaining in an industry-standard footprint. This work represents the design, process development, manufacturing, and characterization of such a system. A microfluidic device manufacturing process was developed to translate the Draper PDMS bilayer microfluidic device[5–7] into a next generation system entirely made of hard plastic. Cyclic olefin copolymer (COC) and polycarbonate thermoplastics were characterized and chosen for their compatibility with drug development applications and large scale manufacturing processes. Hot embossing and thermal bonding procedures were developed that resulted in minimal feature deformation and a robust bond between material layers. Integrated electrical sensors were fabricated in microfluidic channels to quantify transepithelial electrical resistance (TEER) in real time. The sensor design and complex trace routing were demonstrated to be continuous, conductive and fully integrated in the next generation system. The culmination of these design decisions resulted in a hard plastic, bilayer microfluidic device with integrated sensors that is compatible with the industry-standard footprint suited for applications in drug development and disease modeling.