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Three-dimensional microscale hanging drop arrays with geometric control for drug screening and live tissue imaging.

Abstract
Existing three-dimensional (3D) culture techniques are limited by trade-offs between throughput, capacity for high-resolution imaging in living state, and geometric control. Here, we introduce a modular microscale hanging drop culture where simple design elements allow high replicates for drug screening, direct on-chip real-time or high-resolution confocal microscopy, and geometric control in 3D. Thousands of spheroids can be formed on our microchip in a single step and without any selective pressure from specific matrices. Microchip cultures from human LN229 glioblastoma and patient-derived mouse xenograft cells retained genomic alterations of originating tumors based on mate pair sequencing. We measured response to drugs over time with real-time microscopy on-chip. Last, by engineering droplets to form predetermined geometric shapes, we were able to manipulate the geometry of cultured cell masses. These outcomes can enable broad applications in advancing personalized medicine for cancer and drug discovery, tissue engineering, and stem cell research.
AuthorsA Ganguli, A Mostafa, C Saavedra, Y Kim, P Le, V Faramarzi, R W Feathers, J Berger, K P Ramos-Cruz, O Adeniba, G J Pagan Diaz, J Drnevich, C L Wright, A G Hernandez, W Lin, A M Smith, F Kosari, G Vasmatzis, P Z Anastasiadis, R Bashir
JournalScience advances (Sci Adv) Vol. 7 Issue 17 (04 2021) ISSN: 2375-2548 [Electronic] United States
PMID33893093 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).
Topics
  • Animals
  • Cell Culture Techniques (methods)
  • Drug Evaluation, Preclinical
  • High-Throughput Screening Assays (methods)
  • Humans
  • Mice
  • Spheroids, Cellular
  • Tissue Engineering (methods)

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