High Quality Water-soluble Quantum Dots Used For Biomarkers

Semiconductor quantum dots (QDs) have generated an increasing interest due to their narrow and size-tunable emission spectra, broad absorption profiles and high quantum yields. Most chemically synthetic routes to high-quality QDs predominantly employ carboxylic acids, amines, or phosphine oxides with long hydrocarbon chains as capping ligands, which sterically stabilize QDs in hydrophobic solvents. The most important application of QDs is in biological, and the premise is water-soluble QDs. Typical phase transfer of QDs is achieved by replacing the original ligands with specifically designed molecules through a ligand-exchange process, or by cross-linking of QDs with a shell of silanols, or amphiphilic copolymers. Although surface modification based on ligand-exchange reactions has been actively explored in various nanocrystals systems, a generalized and efficient strategy is far from developed. Purpose of this research is obtain high quality QDs base on ligand exchange route.The main work are stated as following:(1) Bifunctional multidentate ligand modified highly stable water-soluble QDsWe have designed and synthesized a multidentate polymer ligand used for water-solubilization of luminescent QDs. The synthesis of the multidentate ligand (PAA-g-MEA) was based on several thiol groups grafted to a linear polymer chain through a simple carboxy-amine coupling reaction between poly(acryl acid)(PAA) and mercaptoethylamine (MEA). Water-soluble QDs capped with these PAA-g-MEA ligands were prepared via ligand exchange from the original hydrophobic ones. The resulting PAA-g-MEA capped water-soluble QDs with relatively small hydrodynamic diameters (12.9nm) and possess higher photoluminescence quantum yields than the initial hydrophobic QDs, extraordinary stability over extended periods of time and over a broad pH range (3-14), salt concentrations (up to saturated NaCl solution), and thermal treatment at100℃.(2) Blending two multidentate ligand with an appropriate proportion to modify highly stable water-soluble QDsA mixed surface ligand system was investigated using two multidentate compound, which has been reported respectively. The derivative of poly(acrylic acid) and derivative of poly(ethylene glycol)(PEG) both contained multithiol were synthesized by facile and convenient routes. The original hydrophobic QDs were successfully transferred into hydrophilic ones by using either or both of the ligand, the PEG segment making QDs water-soluble and biocompatible, the carboxylic group also making QDs water-soluble and available for further bioconjugation. The resulting water-soluble QDs capped with the mixture of two ligand, have relatively small hydrodynamic size, and retain high fluorescence quantum yield of the original hydrophobic QDs. In addition, they exhibit excellent colloidal stability under conditions of wide pH range (2-13), high salt concentration (1M), typical biological buffers and medias, the boiling treatment.(3) Nucleotides modified high-quality water-soluble nanocrystalA general, facile, and reversible nanocrystals (NCs) phase transfer protocol via ligand exchange using nucleotide monophosphates and nucleosides was developed. This phase transfer strategy can be employed on a wide variety of chemically synthesized nanostructured materials including semiconductors, metal oxides and noble metals with different sizes and shapes. The resulting AMP-capped QDs can disperse homogeneously in aqueous or alcohol media retaining high photoluminescence quantum yields. The intrinsic multiple hydrophilic groups and potential multi-dentate coordination in the nucleotide monophosphate ligands endow the nucleotides-and nucleosides-capped QDs with excellent colloidal and photoluminescent stability independent on the pH and ionic strength, minimal hydrodynamic size (7.1nm). More significantly, the water-soluble nucleotides-QDs obtained by ligand exchange treatment can readily undergo secondary surface modification by hydrophobic ligands due to the weak binding affinity of nucleotide monophosphates, allowing fully reversible phase transfer of QDs between organic and aqueous media. The water-soluble QDs capped with nucleotides possess good biocompatible, smaller hydrodynamic size, and excellent colloidal stability, and will play an important role in situ tracer, multi-color experiments, immunoassays and in vivo optical imaging.