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

CPS：TTP 选项：中：协作研究：加密 DNA 的低成本、高通量、网络物理合成

• 批准号: 1740052
• 负责人: Philip Brisk
• 金额: $ 103.91万
• 依托单位: University of California-Riverside
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-10-01 至 2023-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1740052&HistoricalAwards=false
• 关键词: CPS; TTP; Option; Medium; Collaborative

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.

该项目将研究一个新的过程，用于制造合成DNA寡核苷酸的大规模库，该过程被广泛用于基因组学研究，现在被视为长期档案数据存储的媒介。使用微阵列技术合成DNA的当前价格为每碱基10美分，相当于每兆字节的存储空间约3,500美元。 该项目试图使用计算机控制的高通量分类将DNA合成的成本从10美分降低到每个碱的0.007美分。 DNA合成方法还将包括自动数据加密。尽管传统数字数据存储技术的开发（例如硬盘，闪存）在加密的集成之前，作为DNA综合过程的一部分进行加密，可确保将未来的基于DNA的档案存储模式受到强有力的保护。 该项目以系统工程原理和网络物理系统（CPS）的基础为基础。 DNA将在激光活化的微转带芯片（P-CHIP）上合成，该微转带芯片（P-CHIP）通过射频（RF）或光信号传输传输唯一的ID，并且可以用作对DNA合成的固相支持。尤其重要的是设计高通量微流体分辨率/歧管，可以实时迅速对P-CHIP进行迅速排序，并将它们运送到储层中，这些储层将适当的DNA化学性能用于合成并附加下一个寡核苷酸并将其附加到每个P-chip上的序列。 三个12英寸的硅生产晶片载有足够的p-CHIP，以合成5,000,000个独特的DNA序列的库，或者300,000,000个碱基对的基因组。 P-CHIP是化学惰性的，与DNA合成兼容，并且足够致密以允许高速机械分离。工作的智力意义涉及：（1）调查流体模型的算法，用于流经高速微流体P-CHIP分散器/歧管的P-CHIP，包括对商业软件产生的计算流体流动模型的所需校正，（2）为流动性CPS和其启用的100次乘以x乘以x乘以x的创建x的创建（2） 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.

项目成果

Accelerating Simulation of Particle Trajectories in Microfluidic Devices by Constructing a Cloud Database

• DOI: 10.1109/isvlsi.2018.00126
• 发表时间: 2018-01-01
• 期刊: 2018 IEEE COMPUTER SOCIETY ANNUAL SYMPOSIUM ON VLSI (ISVLSI)
• 作者: Wang, Junchao;Fu, Lingxuan;Grover, William H.
• 通讯作者: Grover, William H.

ChemStor: Using Formal Methods To Guarantee Safe Storage and Disposal of Chemicals

ChemStor：使用正式方法保证化学品的安全存储和处置

• DOI: 10.1021/acs.jcim.9b00951
• 发表时间: 2020
• 期刊: Journal of Chemical Information and Modeling
• 影响因子: 5.6
• 作者: Ott, Jason;Tan, Daniel;Loveless, Tyson;Grover, William H.;Brisk, Philip
• 通讯作者: Brisk, Philip

FPGA-based Acceleration of Time Series Similarity Prediction: From Cloud to Edge

• DOI: 10.1145/3555810
• 发表时间: 2022-08
• 期刊: ACM Transactions on Reconfigurable Technology and Systems
• 影响因子: 2.3
• 作者: Amin Kalantar;Zachary Zimmerman;P. Brisk

BioScript: programming safe chemistry on laboratories-on-a-chip

BioScript：在芯片实验室上进行安全化学编程

• DOI: 10.1145/3441686
• 发表时间: 2021
• 期刊: Communications of the ACM
• 影响因子: 22.7
• 作者: Ott, Jason;Loveless, Tyson;Curtis, Chris;Lesani, Mohsen;Brisk, Philip
• 通讯作者: Brisk, Philip

Directed Placement for mVLSI Devices

• DOI: 10.1145/3369585
• 发表时间: 2020-04-01
• 期刊: ACM JOURNAL ON EMERGING TECHNOLOGIES IN COMPUTING SYSTEMS
• 影响因子: 2.2
• 作者: Crites, Brian;Kong, Karen;Brisk, Philip
• 通讯作者: Brisk, Philip