The Development of Point-of-Care Microfluidic Devices for the Detection of Infectious Diseases
Karas, Scott, Chemistry - Graduate School of Arts and Sciences, University of Virginia
Landers, James, Chemistry, University of Virginia
Point-of-care (POC) diagnostics is a discipline focused on using instrumentation or analytical techniques to detect and identify target analytes at or near a patient in need of treatment, whereby the patient is properly diagnosed and provided the necessary medical care. In the past few years, there has been an increased focus on the development and implementation of POC devices to rapidly detect infectious diseases. Microfluidics has assisted in bridging the technology gap to produce inexpensive, portable, and easy to use POC diagnostic devices.
An introduction into POC devices and microfluidics is described in Chapter 1, as well as the relevant literature surrounding their design and method of detection. Additionally, a thorough description of the types of paper-based immunoassays and their integration into microfluidic devices are presented. The work described in Chapter 2 focused on the development of a novel centrifugally-driven orthogonal flow immunoassay (cOFI) disc with a long microfluidic channel which allows for a constant flow rate throughout the duration of the assay. Additionally, the work presented proof-of-concept to detect an infectious disease, Yersinia pestis, on disc. Chapter 3 builds on the cOFI disc design to increase the assay’s sensitivity by increasing the overall sample volume that can be analyzed; by leveraging 3D-printed technology, a large volume sample chamber was developed allowing up to 12 mL of sample to be handled on disc. Therefore, increasing the sensitivity ten times compared to the original disc design in Chapter 2. To further improve on the cOFI device, an automated cOFI system was presented in Chapter 4 that could perform all of the assay steps and the image analysis of the membranes without requiring user input, simplifying the diagnostic testing and meeting the requirements of a POC system. The work presented in Chapter 5 was focused on the design and characterization of a multiplexed flow through assay (FTA). The FTA chip has the potential to detect up to six different target analytes on one membrane from a single sample, without requiring any off-chip sample preparation or external instrumentation.
Finally, Chapter 6 highlights the potential applications and impacts the POC devices described in the previous chapters will have on medical diagnostics, as well as current challenges that need to overcome and future research that needs to be performed.
PHD (Doctor of Philosophy)
Microfluidics, Centrifugal Microfluidics, Infectious Diseases, Biological Warfare Agents, Large Volume, 3D-Printing, Immunoassay, Vertical Flow Immunoassay, Orthogonal Flow Immunoassay, Point-of-Care, Point-of-Need, Diagnostics
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