The Studies Of Preparation And Magnetic Property Control Of Nano Iron Oxides By Continuous Droplet Method

Iron oxide nanoparticles（IONPs）have attracted much attention and research in biomedical fields,including diagnosis and treatment of cancer,magnetic resonance imaging（MRI）and regenerative medicine,due to their unique magnetic properties,biological effects and good biocompatibility.There are many synthesis methods of IONPs,including chemical coprecipitation method,high temperature pyrolysis method,hydrothermal method,sol-gel method,polyol method,etc.Among all the synthesis methods,chemical coprecipitation is the most commonly used method in biomedical field because it does not use any organic solvents,does not need expensive organic precursors,and the preparation process is green and easy to achieve large-scale production.However,the specific coprecipitation formation mechanism of IONPs is not completely clear due to the complex hydrolysis reaction of iron ion in the alkaline environment.Moreover,the process control and the monodispersity and crystallinity of products prepared via coprecipitation method need to be further improved.In view of the above problems,a gas/liquid microreaction unit fluidic device was designed based on the characteristics of the coprecipitation reaction,and the coprecipitation formation mechanism of IONPs was explored by using this fluidic device.The continuous and stable preparation of extremely small iron oxide nanoparticles（ESIONPs）which can be used for T₁-weighted magnetic resonance imaging（T₁-MRI）was realized by using the gas/liquid microreaction unit fluidic device.The main research contents are as follows:1.The gas/liquid microreaction unit coprecipitation synthesis method of IONPs was proposed,and the related fluidic device was designed.In this method,ammonia gas is used as the gas phase reactant,and converges with the iron salt precursor solution in the T-channel to form uniform gas/liquid microunits.The dissolution and mixing of ammonia gas lead the microliquid reach an alkaline p H rapidly,and then co-precipitation reaction occurs.The feasibility of this synthesis method was verified by a series of experiments.2.The phase composition transformation of IONPs formed at the initial stage of room temperature coprecipitation reaction was studied by using the gas/liquid microreaction unit fluidic device.A series of crystalline phases were identified at the initial stage of the coprecipitation reaction, including Fe（OH）₃,α-Fe OOH,Fe₃O₄ andγ-Fe OOH phases.According to the percentage of each crystal phase varies with the reaction time,our work successfully determined that Fe（OH）₃ and α-Fe OOH are the predominant phases initially formed during the coprecipitation reaction,which then transform to Fe₃O₄ in the presence of Fe²⁺ions.3.The influences of reaction time,reaction p H and the valence of Fe ions on the room temperature coprecipitation formation of IONPs in quick mixing mode were studied by using the gas/liquid microreaction unit fluidic device without use coating materials.It was found that the small nanoparticles formed and aggregated promptly in～3 s under alkaline condition（p H 10-11）,and they gradually accumulated and grew into large Fe₃O₄ nanoparticles with the prolongation of reaction time.A similar growth pattern was also observed with the increase of reaction p H from～2.5 to 9.5,and a small amount of poorly crystallized intermediate phases including ferrihydrite,β-Fe OOH andα-Fe OOH were observed.If only Fe³⁺ions participated in the precipitation reaction,ferrihydrite nanoparticels with poor crystallinity and weak magnetic performance would mainly form.However,if only Fe²⁺ions participated in the reaction,the sheet-like green rusts would form firstly,and then the Fe₃O₄ nanoparticles would gradually generate on the surface of green rust as the partial oxidation of Fe²⁺ions.4.The continuos and controllable preparation of ESIONPs was realized by using the gas/liquid microreaction unit fluidic device.The ESIONPs possess high crystallinity and magnetization, keep good dispersion stability in aqueous dispersion,and have good biocompatibility.Under clinical 3T MRI scanner,the ESIONPs exhibited strong T₁-MRI bright signal,high r₁value(4.11 mm^-1·s^-1)and low r₂/r₁ value（7.90）in aqueous dispersion.The ESIONPs also exhibited strong T₁-MRI enhanced effect in the cellular environment,so they can be used for the cell labeling and tracking.In addition,the ESIONPs used for the magnetic resonance angiography（MRA）of mice showed significant bright signal and long blood half-life.Therefore,the ESIONPs is expected to be used as MRA contrast for the clinical diagnosis of angiocardiopathy such as myocardial infarction,atherosclerotic plaque,thrombosis and so on.