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

该项目将研究一种制造大规模合成DNA寡核苷酸文库的新工艺，这种文库广泛用于基因组学研究，目前正在考虑作为长期档案数据存储的媒介。目前使用微阵列技术合成DNA的价格是每个碱基10美分，相当于每兆字节存储大约3500美元。该项目试图通过计算机控制的高通量分选，将DNA合成的成本从每个碱基10美分降低到0.007美分左右。DNA合成方法还将包括自动数据加密。虽然传统数字数据存储技术（如硬盘、闪存）的发展先于加密的整合，但将加密作为DNA合成过程的一部分，确保了未来基于DNA的档案存储模式将得到强有力的保护，免受篡改。该项目建立在系统工程原理和信息物理系统（CPS）的基础上。DNA将在激光激活的微应答器芯片（p-Chip）上合成，该芯片通过射频（RF）或光信号传输唯一的ID，并且可以用作DNA合成的固相支持。特别重要的是高通量微流控分选器/歧管的设计，它可以实时快速分选p-Chip，将它们送到应用适当DNA化学合成并将下一个寡核苷酸附加到每个p-Chip上生长的序列的存储库中。三片12英寸的硅片携带足够的p-Chips来合成一个包含500万个独特DNA序列的文库，或者一个包含3亿个碱基对的基因组。p-Chips是化学惰性的，与DNA合成兼容，并且足够致密，可以进行高速机械分离。这项工作的智力意义包括：(1)研究通过高速微流控p-Chip分选器/歧管的p-Chip流体建模算法，包括对商业软件产生的计算流体流动模型的必要修正；(2)研究流体CPS的协同设计过程及其在创建当前一代（500 x 500 x 100立方微米）和下一代（50 x 50 x 100立方微米）p-Chip分选器/歧管中的应用；(3)实时软件和/或现场可编程门阵列（FPGA）控制的分拣器/歧管，以实现超高通量的DNA合成，(4)支持加密DNA合成，(5)集成的分拣器/歧管和控制机制的商业DNA合成器。

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.