Abstract
In recent decades, magnetic nanoparticle (MNP) has emerged as a promising new material in biomedical applications, particularly in clinical diagnosis and bio-molecule interactions. Due to the high surface area to volume ratio, the high ligand density of MNP surface has significantly enhanced the interaction affinity. Furthermore, the unique magnetic property of MNP facilitates the rapid separation by simple magnetic separation without centrifugation. Because of the great reduction of needed separation time, MNP prevents the bio-degradation of targets resulting from long time operation. In this thesis, diverse functionalized MNP-based platforms have been developed and applied in four important but challenging issues, including immunoassay, site-specific protein modification, screening of small molecules, and bio-separation.
The combination of antibody conjugated MNP and matrix-assisted laser desorption/ionization mass spectrometry (MALDI) successfully established a rapid and accurate method for human serum biomarker detection. To improve the protein conjugation on solid support, boronic acid (BA)-functionalized MNP was used to site-specifically assemble antibody from its Fc domain to maintain the best antibody activity on the solid surface. In addition, maltose-binding protein (MBP) was also immobilized on MNP and microarray specifically from its C terminus to show better maltose binding activity than that of conventional random conjugation MNP. We demonstrated that the protein activity can be conserved after immobilization when the importance of site-specific immobilization is applied. When protein molecule is oriented in an optimal manner on the solid surface, the native conformation is more likely to be preserved, thereby retaining higher activity.
Matrix functionalized magnetic nanoparticles (matrix@MNPs) were synthesized to serve as laser desorption/ionization elements as well as solid-phase extraction probes for simultaneous enrichment and detection of small molecules in MALDI time-of-flight mass spectrometry (MALDI-TOF MS) analysis. MNP@matrix provided a simple, rapid, and reliable quantitative assay for small molecular weight molecules by mass without either the use of an internal standard or an isotopic labeling tag. Furthermore, the affinity extraction of small molecules from complex biofluid was achieved by probe protein-conjugated MNP@matrix without laborious purification.
Owing to the high sensitivity and specificity of MNPs, various functionalized MNPs have been applied in target biomolecule, such as proteins and bacteria, separation from biofluid. Compared with conventional microbeads, functionalized MNPs give a rapid, effective, and specific platform for target molecule purification. In this dissertation research, through appropriate surface modification, MNPs present excellent performance in various biomolecule extractions, ranging from macromolecules (bacteria and proteins) to small molecules (insect suicides and low molecular weight drugs).

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