Drug screening of biopsy-derived spheroids using a self-generated microfluidic concentration gradient

Mulholland, Theresa and McAllister, Milly and Patek, Samantha and Flint, David and Underwood, Mark and Sim, Alexander and Edwards, Joanne and Zagnoni, Michele (2018) Drug screening of biopsy-derived spheroids using a self-generated microfluidic concentration gradient. Scientific Reports, 8. 14672. ISSN 2045-2322

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    Abstract

    Performing drug screening of tissue derived from cancer patient biopsies using physiologically relevant 3D tumour models presents challenges due to the limited amount of available cell material. Here, we present a microfluidic platform that enables drug screening of cancer cell-enriched multicellular spheroids derived from tumour biopsies, allowing extensive anticancer compound screening prior to treatment. This technology was validated using cell lines and then used to screen primary human prostate cancer cells, grown in 3D as a heterogeneous culture from biopsy-derived tissue. The technology enabled the formation of repeatable drug concentration gradients across an array of spheroids without external fluid actuation, delivering simultaneously a range of drug concentrations to multiple sized spheroids, as well as replicates for each concentration. As proof-of-concept screening, spheroids were generated from two patient biopsies and a panel of standard-of-care compounds for prostate cancer were tested. Brightfield and fluorescence images were analysed to provide readouts of spheroid growth and health, as well as drug efficacy over time. Overall, this technology could prove a useful tool for personalised medicine and future drug development, with the potential to provide cost- and time-reduction in the healthcare delivery.