Construction of Tumor Tissue Microarray on a Microfluidic Chip

A microfluidic approach for tumor tissue microarray construction was developed in this work. The 64 cell arrays were prepared by integrating cell introduction, 3D hydrogel scaffold formation and perfusion culture on the microfluidic chip. By using breast cancer MCF-7 cell as a model, cell viabilities, densities, proliferation rates and intracellular pH values were monitored throughout cell culture, and immunohistochemical staining was performed using frozen tissue sections. Breast cancer cells cultured on chip aggregated into tumor spheroids, showing a tissue structure similar to glandular tube. E-cadherin and Vinculin staining indicated the formation of cell-cell and cell-mesenchyme connections. Cancer cells kept proliferating within 15 days after seeding, and the cell viability and cell proliferation rate detected on the 15th day were 85% and 10%, respectively. Intracellular pH assay showed acidification in the cells, which was ascribed to the accumulation of acidic metabolic products caused by shortage of oxygen inside the tumor tissue. The developed microfluidic approach for tumor tissue microarray construction is simple and efficient for tumor research.

Graphical abstractMorphology analysis showed mimicked microenvironment on the microchip. (A) As indicated by the confocal fluorescent imaging, MCF-7 cells aggregated into spheroids in the hrdrogel; (B) HE stained tissue section showed glandular tube structures with incomplete polarity inside the spheroids; (C, D) In-situ immunofluorescence imaging showed the expressions of E-cadherin (C) and Vinculin (D), indicating the formation of cell-cell, and cell-extracellular matrix connections.Figure optionsDownload full-size imageDownload as PowerPoint slide