Despite their simplicity, 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 homogenous and reproducible cell spheroids on a large scale is a labor intensive and slow process compared to monolayer cell cultures. Here, we present a droplet-based microfluidic device for the automated, large-scale generation of homogenous cell spheroids in a uniform manner. Using the microfluidic system, the size of the spheroids can be tuned to 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-polyethylene glycol (rGO-BPEI-PEG) nanocomposite as the PTT agent. Furthermore, we generated uniformly sized neural stem cell (NSC)-derived neurospheres in the droplet-based microfluidic device. We also confirmed that the neurites were regulated by neurotoxins. Therefore, this droplet-based microfluidic device could be a powerful tool for photothermal therapy and drug screening applications.
Kidney organoids derived from the human pluripotent stem cells (hPSCs) recapitulating human kidney are the attractive tool for kidney regeneration, disease modeling, and drug screening. However, the kidney organoids cultured by static conditions have the limited vascular networks and immature nephron-like structures unlike human kidney. Here, we developed a kidney organoid-on-a-chip system providing fluidic flow mimicking shear stress with optimized extracellular matrix (ECM) conditions. We demonstrated that the kidney organoids cultured in our microfluidic system showed more matured podocytes and vascular structures as compared to the static culture condition. Additionally, the kidney organoids cultured in microfluidic systems showed higher sensitivity to nephrotoxic drugs as compared with those cultured in static conditions. We also demonstrated that the physiological flow played an important role in maintaining a number of physiological functions of kidney organoids. Therefore, our kidney organoid-on-a-chip system could provide an organoid culture platform for in vitro vascularization in formation of functional three-dimensional (3D) tissues.
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, magnetically induced thermotherapy, or for any combination of the three. However, it is still a challenge to obtain narrowly dispersed, reproducible particles through a typical lab-scale synthesis when researching these materials. Here, we present a droplet capillary reactor that can be used for the synthesis of magnetic iron oxide nanoparticles. Compared to conventional batch synthesis, the particles synthesized in our droplet reactor have a narrower size distribution and 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.
The miniaturized polymerase chain reaction (PCR) system is not only important for medical applications in remote areas of developing countries, but also important for testing at ports of entry during...
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. Here, we demonstrate a microfluidic, capillary, droplet reactor for the multi-step synthesis of iron oxide/gold core-shell nanoparticles. through 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 (SERS), photothermal therapy, and magnetic resonance imaging (MRi).
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