서강대학교

초록/요약

This thesis relates to the droplet-based microfluidic system for biochemical applications. These systems are tools that have the potential for synthesis of magnetic iron oxide nanoparticles, synthesis of iron oxide/gold core-shell nanoparticles and generation of 3D tumor spheroids. In this thesis, the following three systems were developed. First, we present a droplet capillary reactor that can be used for the synthesis of magnetic iron oxide nanoparticles. Nanoparticles have gained large interest in a number of different fields due to their unique properties. In medical applications, for example, magnetic nanoparticles can be used for targeting, imaging, magnetic induced thermotherapy, or for any combination of the three. However, it is still a challenge to obtain monodispersed, reproducible particles on typical lab scale synthesis when researching these materials. Compared to conventional batch synthesis, the particles synthesized in our droplet reactor are a narrower size distribution and have a higher reproducibility. Furthermore, we demonstrate how the particle size can be changed from 5.2 ± 0.9 nm to 11.8 ± 1.7 nm by changing the reaction temperature and droplet residence time in the droplet capillary reactor. Second, we demonstrate a droplet-based microfluidic feed-back control system for the multi-step synthesis of iron oxide/gold core-shell nanoparticles. The core-shell nanoparticles are promising candidates for theranostic drugs, as they combine different intrinsic properties with a small size and large surface area. However, their controlled synthesis, or the screening and optimization of synthesis conditions are often difficult and labor intensive. Through the precise control over mass and heat transfer, and automatization possibilities, microfluidic devices could be a solution to this problem in a lab scale synthesis. The integration of a transmission measurement at the outlet of the reactor, synthesis results can be monitored in a real-time manner. This allowed for the implementation of an optimization algorithm. Starting from three separate initial guesses, the algorithm converged to the same synthesis conditions in less than 30 minutes for each initial guess. These conditions resulted in diameter for the iron oxide core of 5.8±1.4 nm, a thickness for the gold shell of 3.5±0.6 nm, and a total diameter of the core-shell particles of 13.1±2.5 nm. Finally, applications of the iron oxide/gold core-shell nanoparticles were demonstrated for surface enhanced Raman spectroscopy, photo-thermal therapy, and magnetic resonance imaging. Third, we present a droplet-based microfluidic device for the automated, large scale generation of homogenous cell spheroids in a uniform manner. Despite their simplicity, the monolayer cell cultures are not able to accurately predict drug behavior in vivo due to their inability to accurately mimic cell-cell and cell-matrix interactions. In contrast, cell spheroids are able to reproduce these interactions and thus would be a viable tool for testing drug behavior. However, the generation of the homogenous and reproducible cell spheroids in a large scale is a labor intensive and slow process compared to monolayer cell cultures. Using the microfluidic system, the size of the spheroids can be tuned between 100 and 130 μm with generation frequencies of 70 Hz. We demonstrated the photothermal therapy (PTT) application of brain tumor spheroids generated by the microfluidic device using a reduced graphene oxide-branched polyethyleneimine-polyehtylene glycol (rGO-BPEI-PEG) nanocomposite as a PTT agent.