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 ar...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 130μm 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.展开更多
基金This work was supported by the National Research Foundation of Korea funded by the Ministry of Science and ICT(Grant numbers 2019R1A2C2008863,2016R1A6A1A03012845,and 2019R1I1A1A01041256).
文摘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 130μm 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.
