Microfluidic self-assembly of tumor spheroids for anticancer drug discovery |
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Authors: | Liz Y Wu Dino Di Carlo Luke P Lee |
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Institution: | (1) Biomolecular Nanotechnology Center, Berkeley Sensor and Actuator Center, Department of Bioengineering, University of California, Berkeley, CA 94720, USA |
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Abstract: | Creating multicellular tumor spheroids is critical for characterizing anticancer treatments since it may provide a better
model than monolayer culture of in vivo tumors. Moreover, continuous dynamic perfusion allows the establishment of physiologically relevant drug profiles to exposed
spheroids. Here we present a physiologically inspired design allowing microfluidic self-assembly of spheroids, formation of
uniform spheroid arrays, and characterizations of spheroid dynamics all in one platform. Our microfluidic device is based
on hydrodynamic trapping of cancer cells in controlled geometries and the formation of spheroids is enhanced by maintaining
compact groups of the trapped cells due to continuous perfusion. It was found that spheroid formation speed (average of 7 h)
and size uniformity increased with increased flow rate (up to 10 μl min−1). A large amount of tumor spheroids (7,500 spheroids per square centimeter) with a narrow size distribution (10 ± 1 cells
per spheroid) can be formed in the device to provide a good platform for anticancer drug assays.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
Liz Y. Wu and Dino Di Carlo contributed equally to this work. |
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Keywords: | Tumor spheroids Drug assay Cell culture Microfluidic devices |
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