Surface Modification and 3D Structuring of Quantum Dots for Bioapplications

Abstract

Quantum dots (QDs) with tunable emission wavelength, high emission intensity, high photoluminescence quantum yield (PLQY), and superior photosatbility shed light on wide range of application requiring novel photo emitting materials. In addition, metal surface (e.g. Zn) or hydrophobic ligand of QDs can be used for surface modification, and they can be used as basic building block to make suprastructure enlarged the potential usage of QDs. In this thesis, we focused on bioapplication of QDs based on well-designed sequential process of water solubilization and biofunctionalization. Since the required spec to maximize the performance of QDs are depending on their purpose, we divide this thesis into part I and part II, according to the water solubilization method.

Part I introduced QDs ligand exchange to make them a compact and biocompatible for microenvironmental cell imaging. Ligand exchange is the method of replacing the existing ligand with a new ligand, having a compactness as advantage. At the beginning of research, single molecular ligands were actively studied owing to their compactness and facile functionalization. Nevertheless, the low dispersion stability makes them unsuitable to be used in practical bioapplication. A multidentate ligand consist of an anchor group, a hydrophilic group, and a functional group, taking a responsibility of binding to QDs, increasing water solubility, and giving biofunction, have been widely researched, since each of groups can be designed depending on its application. We selected each component of the multidentate ligand as an element for developing compact and biocompatible QDs, and introduced a protein engineering technique so that a biomolecule (e.g. affibody, antibody) with a desired biofunction could be easily introduced. The synthesized QDs had only ~15 nm in size, indicating they were suitable for use in microenvironment, and showed excellent cell receptor targeting and imaging ability.

Part II performed QDs 3D assembly to synthesize quantum beads (QBs) for developing highly sensitive immunoassay system. QBs, encapsulating several tens to thousands number of QDs in polymer or silica matrix, show surprising emission intensity and high photochemical stability. Although QB-based immunoassay was previously reported, the conventional QBs coated short ligand was easily precipitated in a presence of high salt concentration or acidic pH range, restricting their application. Furthermore, the short ligand showed only limited accessibility on biomolecules, resulted in low immunoassay sensitivity. Brush type ligand, having highly repeated number of functional group, rendered high dispersion stability and plenty of affordable binding sites for biomolecule conjugation. We firstly introduced brush- type ligand coated QBs on lateral flow assay, which is one of the representative immunoassay, and proved the 5 times higher performance than short ligand coated QBs. By combining antibody orientation technique, the LFA performance was additionally enhanced as ~6 times, acheiving 5 pg/mL which is considered as highly enough to be used in detecting several diseases (e.g. cancer, heart disease, malaria) in early stage.

As previously discussed, we developed the novel bioprobe through ligand exchange and 3D assembly of QDs to achieve high performance in cell imaging and immunoassay field. Furthermore, combination with protein engineering techniques improved performance by easily controlling the orientation of biomolecules and enabled the versatile use of QDs in various filed based on facile conjugation with intended biomolecules. We hope that this thesis is used as bible for research on water solubilization and biofunctionalization of QDs for bioapplications.