Engineering Microfluidic Systems to Recapitulate Human Physiology

Abstract

The overarching goal of this dissertation is to engineer cell culture platforms that recapitulate dynamic in vivo microenvironments and enable functional readouts that mimic organ-level physiology. Specifically, efforts were focused on developing novel dynamic cell culture devices, known as organs-on-chips, and integrated platforms to facilitate their use. Despite the potential of organs-on-chips to address challenging problems in biomedical research, the high technical skill required to fabricate and operate these devices has hindered their widespread adoption. An iterative design, build, test methodology was applied to the research and development of microfluidic devices and automated platforms. The dynamics of glucose stimulated insulin secretion function of pancreatic islets informed the initial design of the microfluidic device for organoids. A microfluidic device to recreate biologic barrier functions was originally inspired by the pressure driven filtration that occurs within the kidney glomeruli. These devices were built through subtractive rapid prototyping of noncytotoxic plastic. Human cells were incorporated into the devices. Microfluidic pumps were utilized to generate dynamic flow. The organs-on-chips were then tested to validate cell viability under dynamic culture conditions and the ability to model organ-level functional readouts. Finally, an integrated platform was developed to automate dynamic culture and functional assessments. Together, this research demonstrates that dynamic physiological processes can be modeled in vitro through the development organ-on-chip technology.</p