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Towards automated production and drug sensitivity testing using scaffold‐free spherical tumor microtissues
Author(s) -
Drewitz Maren,
Helbling Marianne,
Fried Nicole,
Bieri Manuela,
Moritz Wolfgang,
Lichtenberg Jan,
Kelm Jens M.
Publication year - 2011
Publication title -
biotechnology journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.144
H-Index - 84
eISSN - 1860-7314
pISSN - 1860-6768
DOI - 10.1002/biot.201100290
Subject(s) - scaffold , reproducibility , biomedical engineering , computer science , cell culture , high throughput screening , computational biology , biology , chemistry , bioinformatics , engineering , chromatography , genetics
Although the relevance of three‐dimensional (3‐D) culture has been recognized for years and exploited at an academic level, its translation to industrial applications has been slow. The development of reliable high‐throughput technologies is clearly a prerequisite for the industrial implementation of 3‐D models. In this study the robustness of spherical microtissue production and drug testing in a 96‐well hanging‐drop multiwell plate format was assessed on a standard 96‐well channel robotic platform. Microtissue models derived from six different cell lines were produced and characterized according to their growth profile and morphology displaying high‐density tissue‐like reformation and growth over at least 15 days. The colon cancer cell line HCT116 was chosen as a model to assess microtissue‐based assay reproducibility. Within three individual production batches the size variations of the produced microtissues were below 5%. Reliability of the microtissue‐based assay was tested using two reference compounds, staurosporine and chlorambucil. In four independent drug testings the calculated IC 50 values were benchmarked against 2‐D multiwell testings displaying similar consistency. The technology presented here for the automated production of a variety of microtissues for efficacy testing in a standard 96‐well format will aid the implementation of more organotypic models at an early time point in the drug discovery process.