Integration of Sample Preparation with Centrifugal Microfluidic Devices for Automation of Clinical and Bioanalytical Assays

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O'Connell, Killian, Chemistry - Graduate School of Arts and Sciences, University of Virginia
Landers, James, AS-Chemistry (CHEM), University of Virginia

Adaptable platforms for automation of sample preparation offer the potential to improve the quality of results in analytical procedures as well as increase analyst productivity. These outcomes are particularly crucial within pharmaceutical and forensic laboratories, as informed decisions regarding drug safety or criminal justice depend upon the results of analytical tests. High throughput sample processing is also a frequent requirement, yet the time-consuming and laborious nature of many preparation procedures represents a serious impediment. Microfluidic devices offer a potential solution for both automating and decentralizing screening assays. However, the integration of sample preparation workflows within microdevices has remained notoriously challenging. Often, highly specialized microfluidic platforms are developed to meet the technological requirements on a single application basis. Although this strategy has led to the creation of many high-performance devices, adoption and implementation are slowed if fabrication remains complex or the overall mechanism is not readily adaptable to new targets. In an effort to redirect from the specialization mindset in favor of flexible modularity, an exploration of functionalized membranes was pursued in the following work.
Chapter 2 initially demonstrates the multiple benefits of employing a chemically and thermally resistant membrane for on-board reagent storage within a polymeric microfluidic device. This approach retained the desirable properties of the original microdevice fabrication method, while also enabling the localization and heating of highly corrosive reagents. Chapter 3 follows on this work utilizing multiple membranes within a fully integrated microdevice intended to automate the preparation of laced cannabis samples, improving the accuracy of illicit drug identification. Chapter 4 highlights the development of a customized enzyme reactor intended for automating sample preparation of therapeutic antibodies prior to LC-MS/MS analysis. This reactor may be reapplied toward new targets by simply changing the immobilized enzyme on the membranes surface. Finally, Chapter 5 discusses the development of a digital image processor for automating data extraction. Beta versions of the processor were employed in the evaluation of a potential chemical sensor array for mixed cannabinoids discrimination.

PHD (Doctor of Philosophy)
centrifugal microfluidic, membrane, sample preparation, chemometric
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