Surface Modification Of Quantum Dots And Their Applications In Tumor Nucleic Acid Markers Detection

As a new class of semiconductor nanomaterials, quantum dots(QDs) are attractive for its unique optical properties. Compared with conventional organic fluorescent dyes and fluorescent proteins, QDs have some advantages,such as broad and effective excitation spectrum, narrow and symmetric emission spectra, high fluorescence intensity, good light stability and size-tunable emission wavelength. Thus, QDs have the increasingly widespread applications in the fields of bio-analytical and imaging. Currently, organic phase synthesis and aqueous phase synthesis are the mainly chemical synthesis methods of QDs. QDs prepared by aqueous phase can be directly used to construct bio-probes, but the fluorescence quantum efficiency and stability are still need to be improved.In this thesis, thiol-containing polymer of multidentate ligands and thiol-functionalized polyacrylic acid microspheres were designed and synthesized, and they were used to modify the surface of aqueous QDs capped with single mercapto ligands. We also explored the QDs’ applications in the detection of microRNA. The main contents are expressed as follows:1. Developping surface modification method for QDs based on novel thiol-containing multidentate polymer ligandSurface modification of the aqueous QDs is very important to the subsequent biological applications, the current methods are few and ineffective. We designed and synthesized a novel thiol-containing multidentate polymer ligand, its multidentate mercapto structure provided a lot of riveting sites for QDs, thereby reduced the detachment of ligand from the QDs’ surface, and significantly improved the stability of quantum dots. It opened up a new method for efficient surface modification of the aqueous phase synthesized QDs.2. Constructing QDs fluorescent composite microspheres based on thiol-functionalized polyacrylic acid microspheresThiol-functionalized polyacrylic acid microspheres were synthesized by precipitation polymerization. The coordination between thiol groups of microspheres and cadmium ions of QDs was used to bind QDs to the surface and internal of the microspheres. The presence of thiol groups can eliminate surface defects and guarantee fluorescence properties of QDs. On the other hand, acrylic made microspheres water-dispersible, and provided reactive functional groups for further bio-functionalization.3. Constructing a highly sensitivive and specific nucleic acid sensor based on quantum dots and magnetic microbeads.A biosensor for tumor markers miRNA was built by taking the advantage of excellent optical properties of QDs and easy separation characteristics of magnetic beads. We used external magnetic field to separate magnetic beads from the detecting system and realized the qualitative and quantitative detection of mi RNA by detecting changes of fluorescence intensity. Experimental results showed that the sensor had high sensitivity and specificity with the detection limit of 1 fM, linear range covered four orders of magnitude, and had potential application in the early detection of lung cancer.