Dissertation/Thesis Abstract

Centrifugal microfluidic platforms towards sample-to-answer nucleic acid diagnostics
by Siegrist, Jonathan Philip, Ph.D., University of California, Irvine, 2009, 207; 3379747
Abstract (Summary)

Microfluidics hold much potential for adapting nucleic acid-based molecular diagnostic techniques onto automated platforms to achieve capabilities and performance far superior to the manual, benchtop methods in use today. Especially for infectious disease diagnostics, there is a drive to create rapid, integrated systems capable of sample-to-answer detection with additional benefits such as lower costs and higher reproducibility. This work focuses on the research, design, and development of centrifugal, microfluidic platforms towards in vitro sample-to-answer applications of nucleic acid-based diagnostics for infectious diseases.

A background on current medical diagnostics is first presented, along with the specific biological analysis steps involved in a typical nucleic acid analysis. Additionally, the advantages of adapting medical diagnostics onto microfluidic platforms are discussed. Next, background information, theory, and history are presented for centrifugal compact-disc (CD)-like technologies, along with a brief overview of the field. Then, novel research on single-function microfluidic platforms for nucleic acid analysis is presented, including a CD-based sample preparation platform, a microfluidic nucleic acid amplification system, and a CD-based platform for DNA detection via microarray. Included in this work is the development of a new type of valve for CD microfluidics, which is modeled analytically and validated experimentally.

The remaining sections present novel research on integration of the single-function platforms into two separate sample-to-answer systems. The first CD-based sample-to-answer platform discussed is focused on single-analyte detection of Anthrax by combination of sample preparation and real-time nucleic acid amplification. The second CD-based sample-to-answer platform presented focuses on multi-analyte detection of a wide panel of respiratory viruses by combining sample preparation, nucleic acid amplification, and DNA microarray detection. In-depth numerical modeling of CD microfluidic behavior is also presented as it pertains to uniform microchamber filling.

In conclusion, future prospects for CD-based sample-to-answer platforms are discussed, along with challenges that remain for the CD platform in general. Finally, a forward-looking vision of a future CD-based sample-to-answer system is presented as motivation for continued work.

Indexing (document details)
Advisor: Madou, Marc
Commitee: Brody, James, Corn, Robert, Lee, Abraham, Tang, William
School: University of California, Irvine
Department: Biomedical Engineering - Ph.D.
School Location: United States -- California
Source: DAI-B 70/11, Dissertation Abstracts International
Subjects: Biomedical engineering
Keywords: Centrifugal, Microfludics, Molecular diagnostics, Nucleic acids, Sample-to-answer
Publication Number: 3379747
ISBN: 9781109491623
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