Beyond the on/off chip trade-off: A reversibly sealed microfluidic platform for 3D tumor microtissue analysis

• Published in: Sensors and actuators. B, Chemical Vol. 274; pp. 393 - 401
• Main Authors: Pitingolo, Gabriele, Nizard, Philippe, Riaud, Antoine, Taly, Valerie
• Format: Journal Article
• Language: English
• Published: Lausanne Elsevier B.V 20.11.2018; Elsevier Science Ltd; Elsevier
• Subjects: Bioengineering; Cell culture; Cellular Biology; Colorectal cancer; Cytotoxicity; Fluorescence; Life Sciences; Microchannels; Microfluidics; Modular chip; Morphology; Scanning electron microscopy; SEM analysis; Spheroid; Tumor microtissue; Tumors; SEM analysis; Fluorescence; Spheroid; Tumor microtissue; Modular chip; Microfluidics
• ISSN: 0925-4005; 1873-3077
• DOI: 10.1016/j.snb.2018.07.166

[Display omitted] •A reversibly sealed microfluidic platform for 3D tumor microtissue formation and analysis is developed.•After the assay, the resealable chip allows selective spheroid retrieval for in-depth analysis.•On and off-chip characterization of 3D microtissue is carried out.•Cytotoxicity effect of drug was analyzed by using three different methods (optical, fluorescence and scanning electron microscopy).•We analyzed the SEM images to study the morphology parameters of spheroids subjected to drug treatments. Nowadays, microfluidic 3D cell culture is widely used to mimic complex microtissue and dynamic environment, performing more realistic in vitro assays for drug testing. Herein, we developed a novel microfluidic platform for tumor microtissue culture, drug response analysis and versatile microscopic characterization. By reversibly bonding the chip, we go beyond the on/off chip tradeoff, which allows us to perform both fluorescence and SEM characterization of tumor microtissues on a simple platform. The microfluidic chip consists of spherical microwells connected via microchannels, bonded through a magnetic system. Colorectal cancer HT-29 cells were cultured as spherical microtissues on chip and their growth kinetics monitored. The cytotoxic activity of Camptothecin was evaluated by in situ live/dead fluorescence staining and quantification of morphology parameters. Finally, we demonstrated the possibility to collect the 3D tumor microtissues and characterize their surface damaged by the drug using scanning electron microscopy. This reversibly sealed microfluidic platform thus enables to grow sets of 3D tumor microtissues in a controlled dynamic microenvinroment, and subsequently to retrieve the 3D tumor microtissues after chemotherapeutic treatment for in-depth analysis.