Lung Cancer Cell–Macrophage Interaction System for Signal Pathway-Based Logic Analysis and Drug Testing

Deciphering and analyzing the signaling pathways formed by multiple molecules during intercellular interactions is crucial for understanding cancer mechanisms and developing anticancer drugs. Currently, most methods for tumor research mainly focus on discrete biomolecules while overlooking the molecular logical relationships based on signal pathways. Here, we present a microfluidic chip-based electrochemical logic analysis (μELA) system that integrates a lung cancer chip, a macrophage chip, a logic gate chip, and an electrochemical (EC) sensing chip. The integrated system allows for the analysis of the logical relationship between miR-21 and miR-29a secreted by lung cancer cells and interleukin-6 (IL-6) secreted by macrophages, as well as the on-chip visualization of the activated NF-κB signaling pathway in the interaction between lung cancer cells and macrophages. In addition, drug testing based on the μELA system verifies that inhibitor combinations targeting lung cancer cell-macrophage interactions are more effective in inducing cell apoptosis than inhibitors that only act on lung cancer cells. This μELA system enables in situ cell culturing, biomarker sensing, automated logic analysis, and signaling pathway-based drug testing. We believe that this innovative and integrated microfluidic system holds great potential for studying cancer mechanisms and drug discovery.