Monitoring pH variation of a 3D breast cancer model in a flow-through microreactor

Cancer is responsible for an estimated 9.6 million deaths in 2018, being the second leading cause of death worldwide.¹ However, due the complexity and diversity of the disease, an effective treatment, with insignificant health risk for the patient, is still not available. Therefore, cost-effective drug testing platforms capable of reproducing the complexity of cancer biology and monitoring its response are urgent and necessary.  We present a novel 3D drug testing platform capable of sustaining a breast cancer model and simultaneously monitor the tumor extracellular pH, which can be used as a diagnostic biomarker for tumor aggressiveness and metastases.²

The platform 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.³ MCF7 breast cancer cells and fibroblasts are dynamically cultured in the 3D microreactor, showing 70% of cell viability at day 15. The extracellular pH measure after day 15 was 5.8, similar value was reported in literature.⁴

The combination of the microreactor, with a 3D tissue engineered tumor model and the 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/w..., (accessed 28 February 2019).

2            M. Chen, C. Chen, Z. Shen, X. Zhang, Y. Chen, F. Lin, X. Ma, C. Zhuang, Y. Mao, H. Gan, P. Chen, X. Zong and R. Wu, Oncotarget, 2017, 8, 45759–45767.

3            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.

4            X. Zhang, Y. Lin and R. J. Gillies, J. Nucl. Med., 2010, 51, 1167–1170.