In Situ Visualization and SERS Monitoring of the Interaction between Tumor and Endothelial Cells Using 3D Microfluidic Networks.

A multifunctional microfluidic platform was demonstrated to monitor the interaction between tumor cells and endothelial cells by integrating a three-dimensional (3D) cell culture unit with a protein detection unit. In such a chip, breast cancer cells MCF7 were seeded into the collagen to form a 3D tumor environment while human umbilical vein endothelial cells (HUVECs) are seeded in the channel next to the collagen matrix. Thus, an in situ growth of angiogenic sprouting can be visualized through fluorescence in the 3D collagen matrix after a coculture of MCF7 and HUVEC after 4 days, which cannot be observed in the 2D culture environment. On the other hand, gold@silver core-shell nanorods were used as surface-enhanced Raman scattering (SERS) immunoprobes for the detection of the secretion of cytokine (vascular endothelial growth factor, VEGF). The limit of detection of the VEGF is 100 pg/mL. Further, as LiCl and bevacizumab can act as a promoter and an inhibitor of VEGF, the dynamic change of the concentration of VEGF under the stimulation of them was monitored by SERS signals. Thus, this integrated SERS microfluidic platform creates opportunity for the fundamental research of interaction between tumors and endothelial cells.

Pharmacokinetics-on-a-Chip Using Label-Free SERS Technique for Programmable Dual-Drug Analysis.

Synergistic effects of dual or multiple drugs have attracted great attention in medical fields, especially in cancer therapies. We provide a programmable microfluidic platform for pharmacokinetic detection of multiple drugs in multiple cells. The well-designed microfluidic platform includes two 2 × 3 microarrays of cell chambers, two gradient generators, and several pneumatic valves. Through the combined use of valves and gradient generators, each chamber can be controlled to infuse different kinds of living cells and drugs with specific concentrations as needed. In our experiments, 6-mercaptopurine (6MP) and methimazole (MMI) were chosen as two drug models and their pharmacokinetic parameters in different living cells were monitored through intracellular SERS spectra, which reflected the molecular structure of these drugs. The dynamic change of SERS fingerprints from 6MP and MMI molecules were recorded during drug metabolism in living cells. The results indicated that both 6MP and MMI molecules were diffused into the cells within 4 min and excreted out after 36 h. Moreover, the intracellular distribution of these drugs was monitored through SERS mapping. Thus, our microfluidic platform simultaneously accomplishes the functions to monitor pharmacokinetic action, distribution, and fingerprint of multiple drugs in multiple cells. Owing to its real-time, rapid-speed, high-precision, and programmable capability of multiple-drug and multicell analysis, such a microfluidic platform has great potential in drug design and development.