Graduate Thesis Or Dissertation

Magnetic particles for selective extraction of trace analytes in microfluidic devices

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  • The development of micro total analysis systems (µTAS), also called “lab-on-a-chip”, or microfluidic analysis systems, is presented in this dissertation. Various research areas, covering subjects from magnetic particles synthesis to novel microchip fabrication techniques, are explored to develop a lab-on-a-chip system capable of performing magnetic bead-based bioassays. These devices are proven not only to be cost-effective (due to their reduced reagent consumption), but also time-efficient (shorter analysis time), and may be disposable (they are inherently compact and inexpensive to produce), making them very attractive to be used in biomedical applications. The research starts with the utilization of functionalized magnetic particles as sorbents for an in-line extraction in confines of capillary columns. The synthesized silica-coated iron oxide particles functionalized with C18 groups were used as reversed-phase sorbents. Magnets were used to locally immobilize these particles inside the capillary. The results showed that extraction, elution, and detection of the analytes were performed sequentially without interruption or need for sample handling. The work continued with the development of bonding techniques for creating polymer-based microfluidic devices through surface modification process. This technique readily produced complete microfluidic chips via plasma oxidation followed by silane reagent treatment (tetraethyl orthosilicate) to facilitate siloxane bonds between the two polymers. It provides a versatile approach to bond dissimilar polymer substrates and between a hard polymer substrate to polydimethylsiloxane or glass. The two previous studies were combined allowing for the integration of magnetic particles in a microfluidic chip format. The benefits of each component were utilized to develop an on-chip aptamer-based fluorescence assay for thrombin detection and quantification based on sandwich ELISA principles. Aptamer-functionalized magnetic beads were utilized to capture the target analyte, while a second aptamer, functionalized with quantum dots, was employed for on-chip detection. Disposable microfluidic devices were employed as the platform to enable rapid and sensitive thrombin detection with the benefits of reduced costs, minimized material consumption, and simplified washing process. This work has opened up a new chapter in the development of magnetic beads-based materials and devices in a wide variety of applications for detection of target proteins of biomedical importance.
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