IN G The Department of Mechanical Engineering presents : The Ph . D . Dissertation Defense of Yanyan Zhang MEMS - based Massively - parallelized Mechanoporation Instrumentation for Ultrahigh Throughput Cellular Manipulation

Many applications in cell biology, genetic engineering, cell-based therapeutics, and drug discovery require precise and safe methods for introducing membrane-impermeable molecules into cells. This can be implemented satisfactorily by microinjection. However, disadvantages of traditional manual microinjection include high degree of operator skill, low throughput and labor-intensiveness. Many studies have focused on developing automated and high -throughput systems for microinjection to address these limitations. However, none have provided sufficient throughput for applications such as ex vivo cell therapy, where manipulation of many millions of cells is required. Herein, we propose an ultrahigh throughput (UHT) mechanoporation concept that seeks to address these limitations. The mechanoporation device is a massively-parallelized MEMS-based platform for passively delivering molecules into living cells via mechanical cell membrane penetration. Studies focusing on device design, fabrication and validation at the proof-of-concept level are presented in this dissertation.