In situ probing of cell–cell communications with surface-enhanced Raman scattering (SERS) nanoprobes and microfluidic networks for screening of immunotherapeutic drugs

Discovering novel drugs for cancer immunotherapy requires a robust in vitro drug screening platform that allows for straightforward probing of cell–cell communications. Here, we combined surface-enhanced Raman scattering (SERS) nanoprobes with microfluidic networks to monitor in situ the cancer–immune system intercellular communications. The microfluidic platform links up immune cells with cancer cells, where the cancer-cell secretions act as signaling mediators. First, gold@silver core–shell nanorods were employed to fabricate SERS immunoprobes for analysis of the signaling molecules. Multiple cancer secretions in a tumor microenvironment were quantitatively analyzed by a SERS-assisted three-dimensional (3D) barcode immunoassay with high sensitivity (1 ng/mL). Second, in an on-chip cell proliferation assay, multiple immunosuppressive proteins secreted by cancer cells were found to inhibit activation of immune cells, indicating that the platform simulates the physiological process of cancer–immune system communications. Furthermore, potential drug candidates were tested on this platform. A quantitative SERS immunoassay was performed to evaluate drug efficacy at regulating the secretion behavior of cancer cells and the activity of immune cells. This assay showed the suitability of this platform for in vitro drug screening. It is expected that the fully integrated and highly automated SERS-microfluidic platform will become a powerful analytical tool for probing intercellular communications and should accelerate the discovery and clinical validation of novel drugs.