Functionalized microfluidic devices for directing and monitoring cell-material interactions

Microfluidics offer an ideal platform for conducting chemical and biological analysis by requiring reduced amounts of materials and space. There is a need to further develop microfluidic technology with respect to cell culture on-device, to allow for complex, high throughput analysis of cell-material interactions related to pharmaceutical and tissue engineering applications. The goal of this dissertation is to contribute to the advancement of microfluidics as tools that can be used to conduct new, hypothesis driven cell culture research.;To address the goals of this dissertation, the Contact Lithographic PhotoPolymerization (CLiPP) system will be used to fabricate polymeric devices. The CLiPP system is based on the use of photopolymers, which, when combined with photolithographic patterning, allows for spatial patterning of materials to create microfluidic channels or features. The CLiPP system also features a living radical component, which allows for multiple materials to be rapidly and covalently attached in sequential photopolymerization steps, to either covalently attach multiple layers of or different materials within microfluidic devices.;Three dimensional porous polymer scaffolds were fabricated and incorporated into microfluidic devices and used as mixers, rapidly responding pH sensitive valves, surface reactors, and as cell culture sites. Multilayer microfluidic devices were fabricated and used for cell culture with uniquely addressable three dimensional cell culture sites. It was shown that microfluidic devices made with the CLiPP system are suitable for cell culture studies.;Being able to modify enclosed microfluidic channels could create more complex and adaptable microfluidic devices. The effects of flow on surface-mediated polymerization were evaluated while photografting poly(ethylene glycol) methacrylate from CLiPP polymer substrate within enclosed channels. Grafting conditions including light intensity, flow rate and surface-bound initiation site concentration were varied while monitoring polymerization progress. General guidelines were developed to provide an understanding of the most important factors affecting polymerization events with flow.;Finally, to be able to fabricate fully integrated, cell culture analysis devices, it is necessary to develop graftable sensing molecules. Poly(ethylene glycol) acrylate succinyl fluorescein phosphate was synthesized and photografted from CLiPP polymer surfaces and shown to respond to alkaline phosphatase.