The Controlled Preparation Of Mono Dispersed, High Saturation Magnetization Superparamagnetic Microspheres And Bio & Medical Application

Superparamagnetic microspheres are widely used in bio or medical areas due to their unique properties. These applications include separation and purification of biomolecule, MRI contrast agent, hyperthermia, biosensor, and targeted drug delivery As specifically required for in vitro and in vivo tests, the current research aims have been focused on: (1) synthesizing mono-dispersed, nano-scale spheres for high sensitivity and efficiency (2) achieving high saturation magnetization for fast and sensitive magnetic signal control, manipulation, and detection, and (3) the surface structure could be designed according to application demands. Aimed at above tendency, this study developed a new controllable process to obtain mono dispersed, nano-scale, superparamagnetic magnetic microspheres with high saturation magnetization, and explore the reaction mechanism and nucleic acid extraction & immunoassay application.(1) Based on analysis of the process of magnetic microspheres by traditional miniemulsion polymerization, the mono-dispersed magnetite/polystyrene microspheres with high saturation magnetization were obtained by combining one-step miniemulsion polymerization and magnetic size sorting technique. The magnetite content of as-synthesized magnetic microspheres is 73wt%, and several groups of magnetic microspheres with mono-dispersed size could be obtained by magnetic size sorting technology.(2) The mono-dispersed magnetite/polystyrene microspheres with high saturation magnetization were obtained by miniemulsion nucleation/emulsion polymerization (double miniemulsion) method which was developed innovatively in this paper. Research results indicate that the preparation of"magnetite nanoparticles/octane"composite droplets is the key issue. Through investigation of double miniemulsion polymerization mechanism, the effect factors to the properties and microcosmic structure of microspheres were clarified, and we found Fe3+ on the surface of magnetite nanoparticles has inhibition effect. On the other hand, the microcomic structure of microspheres could be influenced in the present of octane. with the increase of the content of octane in ferrofluid, the dissymmetrical morphology are more easily be formed. The core/shell structure magnetic maicrospheres could be synthesized using DVB as copolymerization monomer, and dissymmetrical morphology disappeared with increase of DVB concentration.(3) Based on the mechanism of double polymerization, the carboxyl magnetic microspheres were prepared successfully using core/shell magnetic microspheres as core and crylic acid as copolymerization functional monomer. The carboxyl density of as-synthesized microspheres could be adjusted from 0.27mmol/g~0.5mmol/g.(4) Through analysis of effect of heterogeneous nucleation of silica on the morphology of composites microspheres, uniquely combining modified sol-gel technique and double miniemulsion polymerization & magnetite aggregates technique, the mono dispersed silica magnetic composite microspheres with high saturation magnetization were obtained. The silica shell thickness could be controlled by adding different amount TEOS. When we used Fe3O4/PS microspheres as core and the silica thickness is 2nm, the magnetite content of such silica magnetic microspheres is as high as 70wt%. on the other hands, Fe3O4/Silica composite nanospheres with different surface structure and morphology were also synthesized by changing reaction conditions of sol-gel method.(5) When the magnetic field was applied, the as-synthesied Fe3O4/PS/silica microspheres could become chain stable structure and the length of magnetic chian could be adjusted by changing magnetic intensity. The superparamagnetic colloid optical crystal could be formed in the present of applied magnetic field.(6) Nucleic acid extraction by the Fe3O4/Silica composite nanospheres were examined, and the relationship between surface structure and morphology of Fe3O4/Silica composite nanospheres was studied. Results shows that as-synthesized silica magnetic microsphere is a good candidate carriers for nucleic acid extraction. On the other hands, the carboxyl magnetic microsphere was used as signal label in quantitative magnetic lateral flow technique to carry out hCG detection. The results show that the as-synthesized carboxyl magnetic microsphere diameter of 130nm could be well applied in immunoassay.