CPS: TTP Option: Medium: Collaborative Research: Low-Cost, High-Throughput, Cyber-Physical Synthesis of Encrypted DNA

Abstract: The project will research a new process for manufacturing large-scale libraries of synthetic DNA oligonucleotides, which are widely used in genomics research and are now being considered as a medium for long-term archival data storage. The current price for synthesizing DNA using microarray technology is 10 cents per base, equivalent to about $3,500 per Megabyte of storage. This project attempts to reduce the cost of DNA synthesis from 10 cents to around 0.007 cents per base using computer-controlled, high-throughput sorting. The DNA synthesis method will also include automatic data encryption. While the development of conventional digital data storage technologies (e.g., hard disk, flash memory) preceded the integration of encryption, pursuing encryption as part of the DNA synthesis process ensures that future DNA-based archival storage modalities will be robustly protected from tampering. The project builds on systems engineering principles and the foundations of Cyber-Physical Systems (CPS). DNA will be synthesized on a laser-light activated microtransponder chip (p-Chip) that transmits a unique ID by radio frequency (RF) or optical signaling, and can be used as a solid-phase support for DNA synthesis. Of particular importance is the design of a high-throughput microfluidic sorter/manifold, that can rapidly sort p-Chips in real-time, delivering them to reservoirs which apply the appropriate DNA chemistry to synthesize and append the next oligonucleotide to the sequence being grown on each p-Chip. Three 12-inch silicon production wafers carry enough p-Chips to synthesize a library of 5,000,000 unique DNA sequences, or a genome of 300,000,000 base pairs. p-Chips are chemically inert, compatible with DNA synthesis, and dense enough to allow high-speed mechanical separation. The intellectual significance of the work involves: (1) investigation of fluid modeling algorithms for p-Chips flowing through the high-speed microfluidic p-Chip sorter/manifold, including the needed corrections to the computational fluid flow models produced by commercial software, (2) investigation of a co-design process for fluidic CPS and its application to the creation of a sorter/manifold for current-generation (500 x 500 x 100 cubic micrometers) and next-generation (50 x 50 x 100 cubic micrometers) p-Chips, (3) real time software and/or Field Programmable Gate Array (FPGA) control for the sorter/manifold to enable ultra-high throughput DNA synthesis, (4) support for encrypted DNA synthesis, and (5) integration of the sorter/manifold and control mechanism into a commercial DNA synthesizer.