DROPLET MAGNETOFLUIDIC TECHNOLOGY FOR THE DELIVERY OF MOLECULAR DIAGNOSTICS AT THE POINT OF CARE
Shin, Dong Jin
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Molecular diagnostic techniques play an increasingly important role in modern medicine. The introduction of highly sensitive and rapid analytical techniques for detection of specific nucleic acid sequences continue to establish new standards of care in areas of emergency care such as pathogen identification. Ongoing research in nucleic acid biomarkers for various types of cancer and neurodegenerative conditions highlight the increasing role that molecular diagnostics will play in the future of medicine. Harnessing these technologies for diagnostic applications at the point of care has the potential to enhance the efficiency of diagnosis and treatment via reduction in both the cost and turnaround time of diagnostic testing at all levels of healthcare delivery. However, the complexity of conventional workflow for sample and reagent handling presents a conceptual hurdle in developing a robust and cost-effective system for point of care diagnostics. A promising solution may be found in droplet magnetofluidic technology. Past research in this field has demonstrated the potential of unique fluidic control mechanism facilitated solely by magnetic particles. Association, dissociation and transport of sessile droplets on hydrophobic substrates suggest a mode of fluid handling that is quite foreign to conventional approaches involving pneumatics or centrifugation. Indeed, investigators were not ignorant to the ramifications of this technology in medicine. With the advent of ‘smart’ particles with a magnetizable core whose surfaces could be used to capture and transport specific biomolecules, droplet magnetofluidics is well-poised to bring the pieces together and usher in a new workflow paradigm for biomolecular assays – one which is more portable and simpler to operate. This thesis investigates the use of droplet magnetofluidics as an enabling technology for point of care diagnostics. Following an introduction to the fundamentals of droplet magnetofluidic kinematics, we conceptualize a novel assay paradigm referred to as ‘single-stream assay workflow’ describing a linear workflow driven by analyte capture and transport on a movable magnetic particle cluster. Chapters 2 and 3 illustrate examples of single-stream bioassays that are enabled by the droplet magnetofluidic process for genetic and epigenetic biomarker analysis. Afterwards, we expand our investigation to various components of a complete platform, namely conceptualization and design of a cartridge and an instrument for process automation. Chapter 4 illustrates an example of process integration enabled by a combination of droplet magnetofluidic cartridge and a programmable magnetic actuator. Chapter 5 provides a discussion of design considerations for various aspects of the platform including the cartridge, instrument and the assay, with an emphasis on factors that must be considered in order to bridge the gap between a proof-of-concept and a field-ready platform. Lastly, we integrate our findings in order to develop a user-friendly diagnostic platform for the evaluation of droplet magnetofluidic workflow in a clinical setting. In Chapter 6, we illustrate a smartphone-based mobile nucleic acid testing station for the evaluation of chlamydia infection in emergency room setting. We will conclude our report with a discussion of future directions for droplet magnetofluidic technology in point of care testing. It is our hope that these findings will inspire the readers to appreciate the wide range of academic and commercial opportunities that droplet magnetofluidics presents to the biomedical field.