Abstract
Multicellular spheroids are an important 3-dimensional cell culture model that reflects many key aspects of in vivo microenvironments. This paper presents a scalable, self-assembly based approach for fabricating microcavity substrates for multicellular spheroid cell culture. Hydrophobic glass microbeads were self-assembled into a tightly packed monolayer through the combined actions of surface tension, gravity, and lateral capillary forces at the water-air interface of a polymer solution. The packed bead monolayer was subsequently embedded in the dried polymer layer. The surface was used as a template for replicating microcavity substrates with perfect spherical shapes. We demonstrated the use of the substrate in monitoring the formation process of tumor spheroids, a proof-of-concept scale-up fabrication procedure into standard microplate formats, and its application in testing cancer drug responses in the context of bone marrow stromal cells. The presented technique offers a simple and effective way of forming high-density uniformly-sized spheroids without microfabrication equipment for biological and drug screening applications.
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Acknowledgments
We thank Dr. Robert A. Weinberg for the HMLER cells, and Peter Waterman for assistance with in vitro bioluminescence imaging. This work was supported in part by National Institutes of Health Grants R01EB012521 (B.P.) and K01DK087770 (B.P.), and also by Massachusetts General Hospital Fund for Medical Discovery 2011A053483 (K.S.).
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Shen, K., Lee, J., Yarmush, M.L. et al. Microcavity substrates casted from self-assembled microsphere monolayers for spheroid cell culture. Biomed Microdevices 16, 609–615 (2014). https://doi.org/10.1007/s10544-014-9863-3
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DOI: https://doi.org/10.1007/s10544-014-9863-3