Enabling technologies for nucleic acid sample-to-answer centrifugal microfluidics

Researchers have adopted the centrifugal microfluidic platform for advanced biomedical analysis since the technology's inception over 40 years ago. While primarily developed for blood analyte analysis and immunoassay development, recent advances in centrifugal microfluidics poise the platform to enter the realm of sample-to-answer diagnostics.;Sample-to-answer technology presents opportunity to advance the state-of-the-art of infectious disease pathology, where a bacteria or virus's unique molecular sequence (nucleic acid) is used to identify the pathogen. Traditionally, each of complex steps of nucleic acid analysis is performed on large, individual machines that require operator assistance and take extended periods of time to complete. Sample-to-answer systems miniaturize, integrate and automate the assays in a single device to produce results rapidly.;Centrifugal microfluidics offer various benefits over other microfluidic platforms for a sample-to-answer nucleic acid analysis system because the use of disposable rotors allows integrated "hands-free" liquid processing in microfluidic networks based on centrifugal forces.;However, centrifugal forces alone cannot create the conditions needed for complex nucleic acid processing. Fundamental challenges remain for such systems related to space (the complete fluidic network must be contained in the radius of a disc) and biological processing (a spinning disc alone cannot establish the environment needed for assay processes like cell disruption, nucleic acid amplification, and fluorescence detection).;The work represented in this dissertation serves to recognize these challenges and to provide solutions to enable the creation of an integrated nucleic acid analysis system on a centrifugal microfluidic platform. The solutions were examined for their simplicity, ability to be integrated in the centrifugal platform and assimilation with mass production techniques. The work includes innovations such as novel pneumatic valving to increase usable area on the disc, the incorporation of magnetic materials to induce stringent pathogen lysis, and a novel non-contact heating system for temperature control of a rotating platform. A proof-of-principle concept for an integrated centrifugal nucleic acid analysis rotor and instrument based on these advanced is also presented.