Tumor-on-a-chip for pH monitoring of a 3D breast cancer model
Abstract
Cancer is responsible for an estimated 9.6 million deaths in 2018, being the second leading cause of death worldwide.1 However, due to the complexity and diversity of the disease, an effective treatment, with insignificant health risk for the patient, is still not available. Continuous extracellular pH monitoring of in vitro 3D tumor models, produced to mimic in vivo conditions, can revolutionize the drug testing industry and improve our understanding of cancer biology. This work reports a novel 3D-tumor-on-a-chip capable of continuous extracellular pH measurement for a period of 15 days.
The chip consists of 300 µl central chamber, where 3D gellan gum matrix measuring 6.6 ± 0.3 x 4.9 ± 0.5 mm is inserted, and tumor cells are cultured. The micro-reactor allows controlled flow rates mimicking in vivo tumor microenvironment. In addition to continuous monitoring of pH, since it contains three integrated electrodes for voltammetry measurements. “Spongy-like” hydrogels fabricated using gellan gum are highly porous, capable of 100% recovery after deformation, presenting 12 months of-the-shelf stability. The chemistry of gelan gum and microstructure of the prepared hydrogels allow the entrapment, growth and proliferation of cells.2 MCF7 breast cancer cells and fibroblasts are dynamically cultured in the 3D tumor-on-a-chip, showing 70% of cell viability at day 15. The extracellular pH measure after day 15 was 5.8, similar value was reported in literature.3
The combination of the flow-through device, with a 3D tissue engineered tumor model and the incorporated electrodes makes this platform a potential tumor-on-chip device for monitoring the response of personalized tumor models to drugs.
1 Cancer Research UK, Worldw. Cancer Mortal. Stat., https://www.cancerresearchuk.org/health-professional/cancer-statistics/worldwide-cancer/mortality, (accessed 28 February 2019).
2 L. P. da Silva, M. T. Cerqueira, R. A. Sousa, R. L. Reis, V. M. Correlo and A. P. Marques, Acta Biomater., 2014, 10, 4787–4797.
3 X. Zhang, Y. Lin and R. J. Gillies, J. Nucl. Med., 2010, 51, 1167–1170.