Centrifugal Microfluidics Based Point Of Care Diagnostics At Resource Limited Settings PDF Download

Microfluidic diagnostic systems are positioned to revolutionize healthcare by enabling the miniaturization and integration of complex diagnostic analyses into platforms that can deliver fast, low-cost diagnostic results and minimize the burden at the point-of-care, serving populations at sites that are remote, resource-limited, and lack access to large hospital laboratory technologies and specialized medical technicians. In order to be successful, the design of novel platforms for microfluidic diagnostics must therefore attend to real-world scenarios of use and consider sample-to-answer viability. Arguably one of the greatest challenges for point-of-care microfluidic diagnostics is sample preparation. While a rich research stream has pushed the frontiers of microfluidic systems, demonstrating their viability in achieving rapid results with miniscule samples, the real-world sample concerns have received little attention. These sample-related properties present unique challenges to the design of microfluidic diagnostic systems and are vital to the success of point-of-care diagnostics. This dissertation contributes to the emerging field of point-of-care microfluidic diagnostic systems through the development of two novel centrifugal microfluidic platforms that address the significant challenges of real-world sample properties. It provides a detailed account of the design of two integrated microfluidic systems: 1) a blood sample preparation disc and 2) an automated PCR analysis disc. Together these two systems provide a case for sample-driven design by addressing and overcoming significant sample-related challenges. The first disc design addresses the unique requirements of a large-volume sample and the second highlights engineering problems associated with low-concentration samples. The dissertation presents work in the design and development of these systems and explores fundamental engineering implications of sample-driven design. It first presents the motivation for sample-to-answer nucleic acid diagnostic systems and the need for attention to sample-driven design concerns by exploring the benefits and challenges of adapting diagnostic systems onto point-of-care microfluidic platforms. Background information on the history and current state-of-the-art in compact-disc microfluidics technologies, practices and theory is provided. Next, the motivation for sample-driven design is discussed in further depth through its application to large-volume and low-concentration sample device design including in-depth modeling of CD microfluidic behavior as it pertains to uniform filling of and dynamic temperature distributions within a microchamber. Novel research is then presented on 1) a centrifugal microfluidic platform for large-volume blood sample preparation and 2) a centrifugal microfluidic platform for real-time PCR amplification for low-concentration nucleic acid sample detection. Finally, an outlook on the future of point-of-care microfluidic systems is discussed along with future work needed to fully realize the vision for the systems presented here.