Secure Cyber-Physical DNA Manufacturing for Life Science Applications and Ultra-Long-Term Data Storage

This first-year project will develop a cyber-physical co-design process and apply it to the manufacturing of large-scale libraries of synthetic DNA oligonucleotides. Synthetic DNA plays an essential role in genomics research, and is poised for widespread consumption if its costs can be lowered dramatically, as large libraries of different DNA sequences are particularly useful in genetic analysis. DNA is also being investigated as a high-density medium for archival storage of digital data. To meet the needs of both genomics researchers and DNA-based storage systems, this project will investigate DNA encryption during synthesis and study the susceptibility of DNA synthesis technologies to side-channel attacks. 

Specifically, this project will apply the co-design process to create a novel high-throughput real-time sorter for p-Chips (see Fig. 1), laser light- activated silicon microtransponder chips, developed by project partner, PharmaSeq, Inc., which can be used as a solid-phase support for DNA synthesis. The sorter rapidly sorts hundreds of p-Chips into four reservoirs, each of which performs the chemistry necessary to append an A, C, G, or T base to the unique oligonucleotide sequence being grown on each p-Chip (see Fig. 2). Under this new DNA synthesis paradigm, the throughput of the sorter, rather than the DNA chemistry itself, becomes the overall bottleneck in the system. 

The current price for synthetic DNA is approximately 10 cents per base using microarrays, which is prohibitively costly for applications that require thousands of unique DNA sequences. We project that this project can reduce the cost per base of synthetic DNA to as low as 7x10-3 cents per base using high-throughput sorting as proposed here. We also plan to show that the software controlling the system can easily be modified to produce encrypted DNA, and that the proposed sorting system is far more robust to side channel attacks than traditional methods of DNA synthesis.