High content drug screening of primary cardiomyocytes based on microfluidics and real-time ultra-large-scale high-resolution imaging.

High content screening (HCS) plays an important role in biological applications and drug development. Existing techniques fail to simultaneously meet multiple needs of throughput, efficiency in sample and chemical consumption, and real-time imaging of a large view at high resolution. Leveraging advances in microfluidics and imaging technology, we setup a new paradigm of large-scale, high-content drug screening solutions for rapid biological processes, like cardiotoxicity. The designed microfluidic chips enable 10 types of drugs each with 5 concentrations to be assayed simultaneously. The imaging system has 30 Hz video rate for a centimeter filed-of-view at 0.8 μm resolution. Using the HCS system, we assayed 12 small molecules through their effects on the Ca2+ ion signal of cardiomyocytes. Experimental results demonstrated the unparalleled capability of the system in revealing the spatiotemporal patterns of Ca2+ imaging of cardiomyocytes, and validated the cardiotoxicity of certain molecules. We envision that this new HCS paradigm and cutting-edge platform offer the most advanced alternative to well-plate based methods.