Semiconductor technology has contributed to the exponential reduction in the cost of gene sequencing, leading to the boom of genomics. Gene synthesis, a technology as important as sequencing, however, is significantly lagging behind, manifested by the five orders-of-magnitude higher cost compared to sequencing, and thus remains a key bottleneck in molecular biology. Dr. Xin Zhao leads an interdisciplinary team using semiconductor technologies including CMOS, MEMS, and microfluidics to achieve ultra-high-throughput oligo synthesis and gene assembly, potentially revolutionizing gene synthesis. Dr. Zhao’s Ph.D. study focused on semiconductor technology, demonstrating the world's smallest vertical transistor with the highest performance based on III-V materials and top-down fabrication techniques. His device design concepts matched the ideal transistor structure for the next 20 years proposed by IRDS in 2017. After graduation, Xin began to explore the intersection between semiconductors and molecular biology with the support of NIH grants.
Traditional gene synthesis relies on 96-well plates, with low throughput, high reagents consumption, and labor-intensive processes, resulting in high synthesis cost. Microelectrode arrays made on the surface of silicon chips by CMOS and MEMS drastically improve the oligo synthesis throughput and reduces reagent consumption, thereby enabling orders-of-magnitude cost reduction in oligo synthesis. In addition, CMOS can accurately control single microelectrodes among million and even billion ones, enabling purification and assembly of oligos on chip, which can potentially realize ultra-high-throughput long-chain DNA synthesis. This is expected to disrupt downstream fields such as synthetic biology, biopharmaceutical, and DNA data storage.