Microfluidic Arrays of Breast Tumor Spheroids for Drug Screening and Personalized Cancer Therapies

Abstract

One of the obstacles limiting progress in the development of effective cancer therapies is the shortage of preclinical models that capture the dynamic nature of tumor microenvironments. Interstitial flow strongly impacts tumor response to chemotherapy; however, conventional in vitro cancer models largely disregard this key feature. Here, a proof of principle microfluidic platform for the generation of large arrays of breast tumor spheroids that are grown under close-to-physiological flow in a biomimetic hydrogel is reported. This cancer spheroids-on-a-chip model is used for time-and labor-efficient studies of the effects of drug dose and supply rate on the chemosensitivity of breast tumor spheroids. The capability to grow large arrays of tumor spheroids from patient-derived cells of different breast cancer subtypes is shown, and the correlation between in vivo drug efficacy and on-chip spheroid drug response is demonstrated. The proposed platform can serve as an in vitro preclinical model for the development of personalized cancer therapies and effective screening of new anticancer drugs.

Computational Modelling and Big Data Analysis of Flow and Drug Transport in Microfluidic Systems: A Spheroid-on-a-Chip Study

“…The experimental MF device contained 200 MCTSs in the microwells that were organized in four parallel rows ( Figure 4A ). The microwells were connected to a common channel used to supply cell culture medium and drug treatment [for more details on fabrication, MCTS formation, and cell staining protocols see Supplementary Material and ( Chen et al, 2021 ; Prince et al, 2021 )]. The cell suspension occupied 100% of the microwells in the form of cell-laden droplets; MCTSs formed within 72 h of cell culture.…”

Trends in Droplet Microfluidics: From Droplet Generation to Biomedical Applications

“…Our group has developed various MF strategies for cell encapsulation, which utilized both hydrodynamic junctions , and hydrodynamic traps. − Emulsification using hydrodynamic junctions enables the generation of cell-laden droplets with a high frequency. Furthermore, several MF droplet generators can be combined to work in parallel.…”

“…Microgels generated by droplet MFs were used for drug delivery and the delivery of vascular endothelial growth factor to ischemic muscle sites . Recently, we developed MF spheroid-on-a-chip platforms for the generation of multicellular spheroids and organoids, which were utilized for coculturing cells, screening active ingredients, and modeling drug delivery to multicellular spheroids. − …”

Recent advances in spheroid-based microfluidic models to mimic the tumour microenvironment

“…Prince et al developed a device that is able to form tumour spheroids uniformly under close-to-physiological flow conditions within a microfluidic device. 38 The use of flow in this device provides longer culture durations of spheroid culture, model of dynamic drug conditions, and sequential testing of drugs, mimicking clinical pharmacokinetics.…”