Generation of tumor spheroids using a droplet-based microfluidic device for photothermal therapy

초록

Mass production of miniature medical models A microfluidic device for the efficient production of three-dimensional 'spheroid' cell cultures could accelerate the discovery and testing of therapeutic agents. These small clumps of cells can better recapitulate the physiology of the tissue environment than two-dimensional cultures, but are challenging to produce in a high-throughput fashion. Researchers led by Prof. Bong Geun Chung of Sogang University, Seoul, Korea have now developed a system that can generate 42,000 spheroids/h with minimal user intervention. As an initial demonstration, they produce brain tumor-derived spheroids, and use these to test the cancer-killing efficacy of a therapy based on heated graphene-based nanoparticles. Prof. Chung and colleagues subsequently employ their device to assess the detrimental effects of the neurotoxin thapsigargin on neural stem cell-derived spheroids, highlighting the potential value of this platform for high-throughput cell screening assays. 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 mu m 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.

키워드