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Issue 3, 2016

Generation and functional assessment of 3D multicellular spheroids in droplet based microfluidics platform

Author affiliations

Abstract

Here we describe a robust, microfluidic technique to generate and analyze 3D tumor spheroids, which resembles tumor microenvironment and can be used as a more effective preclinical drug testing and screening model. Monodisperse cell-laden alginate droplets were generated in polydimethylsiloxane (PDMS) microfluidic devices that combine T-junction droplet generation and external gelation for spheroid formation. The proposed approach has the capability to incorporate multiple cell types. For the purposes of our study, we generated spheroids with breast cancer cell lines (MCF-7 drug sensitive and resistant) and co-culture spheroids of MCF-7 together with a fibroblast cell line (HS-5). The device has the capability to house 1000 spheroids on chip for drug screening and other functional analysis. Cellular viability of spheroids in the array part of the device was maintained for two weeks by continuous perfusion of complete media into the device. The functional performance of our 3D tumor models and a dose dependent response of standard chemotherapeutic drug, doxorubicin (Dox) and standard drug combination Dox and paclitaxel (PCT) was analyzed on our chip-based platform. Altogether, our work provides a simple and novel, in vitro platform to generate, image and analyze uniform, 3D monodisperse alginate hydrogel tumors for various omic studies and therapeutic efficiency screening, an important translational step before in vivo studies.

Graphical abstract: Generation and functional assessment of 3D multicellular spheroids in droplet based microfluidics platform

Supplementary files

Article information


Submitted
21 Sep 2015
Accepted
14 Dec 2015
First published
14 Dec 2015

Lab Chip, 2016,16, 497-505
Article type
Paper

Generation and functional assessment of 3D multicellular spheroids in droplet based microfluidics platform

P. Sabhachandani, V. Motwani, N. Cohen, S. Sarkar, V. Torchilin and T. Konry, Lab Chip, 2016, 16, 497 DOI: 10.1039/C5LC01139F

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