An open-space microfluidic chip with fluid walls for online detection of VEGF via rolling circle amplification

Despite traditional poly-dimethyl siloxane (PDMS) microfluidic devices having great potential in various biological studies, they are limited by sophisticated fabrication processes and low utilization. An easily controlled microfluidic platform with high efficiency and low cost is desperately required. In this work, we present an open-space microfluidic chip with fluid walls, integrating cell culture and online semi-quantitative detection of vascular endothelial growth factor (VEGF) via rolling circle amplification (RCA) reaction. In comparison with conventional co-culture detecting platforms, this method features the prominent advantages of saving reagents and time, a simplified chip fabrication process, and avoiding additional assistance for online detection with the help of an interfacial tension valve. On such a multi-functional microfluidic chip, cells (human umbilical vein endothelial cells and malignant glioma cells) could maintain regular growth and cell viability. VEGF could be detected with excellent specificity and good linearity in the range of 10-250 pg mL^-1. Meanwhile, VEGF secreted by malignant glioma cells was also detected online and obviously increased when cells were stimulated by deferoxamine (DFO) to mimic a hypoxic microenvironment. The designed biochip with fluid walls provides a new perspective for micro-total analysis and could be promisingly applied in future clinical diagnosis and drug analysis.