A novel hanging spherical drop system for the generation of cellular spheroids and high throughput combinatorial drug screening

We propose a novel hanging spherical drop system for anchoring arrays of droplets of cell suspension based on the use of biomimetic superhydrophobic flat substrates, with controlled positional adhesion and minimum contact with a solid substrate. By facing down the platform, it was possible to generate independent spheroid bodies in a high throughput manner, in order to mimic in vivo tumour models on the lab-on-chip scale. To validate this system for drug screening purposes, the toxicity of the anti-cancer drug doxorubicin in cell spheroids was tested and compared to cells in 2D culture. The advantages presented by this platform, such as feasibility of the system and the ability to control the size uniformity of the spheroid, emphasize its potential to be used as a new low cost toolbox for high-throughput drug screening and in cell or tissue engineering.

The authors thank the precious help of Alessandra Zonari and Rui Domingues for capturing the confocal images. The authors acknowledge the financial support from the FCT- Fundação para a Ciência e para a Tecnologia through the Ph.D. grants with the references SFRH/BD/73119/2010, SFRH/BD/ 69529/2010 and SFRH/BD/71396/2010. We acknowledge the financial support of FEDER through the program Operacional Factores de Competitividade – COMPETE and from FCT – the Fundação para a Ciência e a Tecnologia under the project PTDC/CTM-BIO/1814/2012. We also thank the support by the European Research Council grant agreement ERC-2012-ADG 20120216-321266 for the project ComplexiTE.