Petr Panuška, Jiří Smejkal, Marcel Štofik, Zuzana Žmudová, Klára Španbauerová, Jaromír Havlica, Václav Harrandt, Stanislav Vinopal, Petr Aubrecht, Jan Malý
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引用次数: 0
Abstract
In the evolving landscape of cancer research, 3D cell cultures, particularly tumor cell spheroids, are increasingly preferred in drug screening due to their enhanced mimicry of in vivo tumor environments, especially in drug resistance aspects. However, the consistent formation of uniform spheroids and their precise manipulation remain complex challenges. Among various methodologies, droplet microfluidics emerges as a highly effective approach for tumor spheroid formation. This paper introduces a novel, multifaceted microfluidic system that streamlines the entire spheroid cultivation process: (i) generating tumor spheroids from cell suspensions within individual droplets, (ii) merging these droplets into a continuous aqueous phase once spheroid formation is complete, and (iii) transferring the spheroids to a specialized cultivation area within the chip, equipped with trapping elements for extended cultivation in perfusion mode. Remarkably, this process requires no hydrogel encapsulation or external handling, as all operations are conducted within the microfluidic chip. Fabricated from the innovative OSTE+ (off-stoichiometry thiol-ene epoxy) polymer, the chip is designed for repeated use. To show its efficacy, we successfully formed spheroids from MCF-7, GAMG, and U87 cell lines in our system and compared them with spheroids prepared by a traditional agarose microwell method. Additionally, our methodology has successfully enabled the in-chip release of spheroids from droplets, followed by their effective trapping for subsequent cultivation, a process we have exemplified with MCF-7 spheroids. To our knowledge, this research represents the first instance of a fully integrated droplet microfluidic platform achieving scaffoldless tumor spheroid formation and handling. Our method holds promise for improving high-throughput, automated procedures in the formation, transfer, and cultivation of tumor cell spheroids.
期刊介绍：
BioChip Journal publishes original research and reviews in all areas of the biochip technology in the following disciplines, including protein chip, DNA chip, cell chip, lab-on-a-chip, bio-MEMS, biosensor, micro/nano mechanics, microfluidics, high-throughput screening technology, medical science, genomics, proteomics, bioinformatics, medical diagnostics, environmental monitoring and micro/nanotechnology. The Journal is committed to rapid peer review to ensure the publication of highest quality original research and timely news and review articles.
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