SemiSynBio-II: Hybrid Bio-Electronic Microfluidic Memory Arrays for Large Scale Testing and Remote Deployment

SemiSynBio-II：用于大规模测试和远程部署的混合生物电子微流控存储器阵列

基本信息

批准号：
2027045
负责人：
Douglas Densmore
金额：
$ 149.76万
依托单位：
Trustees of Boston University
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2020
资助国家：
美国
起止时间：
2020-10-01 至 2024-09-30
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=2027045&HistoricalAwards=false
关键词：
SemiSynBio II Hybrid Bio Electronic

项目摘要

The ability to record events (“memory”) is a crucial part of many complex systems. Recording events allows these systems to modify their behavior based on previous interactions, report on their history, or communicate local information to a global community. Biological systems will benefit greatly from the creation of memory elements. Biological memories in bacterial or mammalian cells could be used to monitor a person’s microbiome, develop smart materials that respond to the environment, or create specialized sensors that react to biotoxins. Biological memories in living cells themselves require a controlled environment. This environment not only ensures their long-term survival and viability but also allows for the controlled reading and writing of the memory. Reading and writing will ultimately be how these systems are “programmed” and how the data they collect can be acted upon. This project creates novel bio-memories using devices that move small amounts of liquids (microfluidics). Microfluidics are used to test in parallel many biological-memory configurations to determine which are the best at testing specific environmental signals (e.g. toxins, metals, hormones). The best of these memories are then integrated with low-cost, embedded electronics that can read their outputs as well as control the microfluidic environments housing the memories and allowing external signals to “write” information in the memories. Biological memories, microfluidics, and electronics together form what is called “Hybrid Bio-Electronic Microfluidic Memory Arrays”. These devices will explore numerous interdisciplinary challenges and create opportunities for exploring applications at the boundaries of computer science, synthetic biology, and materials science. To maximize this project’s impact, all of the research including the microfluidic and electronics designs and software will be made open source. All genetic memory elements will be provided to the scientific community. More than 48 undergraduate students will be mentored during the project period via NSF sponsored programs and summer research programs at Boston University. This project has a three-phase structure, where in the first phase biological memories are developed with the aid of a high-throughput, electronically augmented microfluidic screening platform. Recombinase enzymatic reactions on DNA will act as the irreversible memories while epigenetic, chromatin modifications will act as the reversible mechanism. This phase will involve the creation of 1000’s of potential memory elements. In the second phase, the top candidates from the first phase are combined in a massively parallel, highly integrated microfluidics platform to develop the eventual deployed microfluidic as well as establishing the operating and control conditions needed for the memories. Finally, in phase three, a small-scale deployment environment is created to observe and tune the performance of the newly created Hybrid Bio-Electronic Microfluidic Memory Arrays in an aquatic deployment scenario meant to replicate real-world bio-sensing applications for heavy metals and other environmental signals. These phases explicitly address three bio-memory challenges (create, control, and deploy) using state-of-the-art biological reversible and irreversible memories, droplet microfluidics, and customized embedded semiconductor-based electronics.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

记录事件的能力（“记忆”）是许多复杂系统的重要组成部分，记录事件允许这些系统根据之前的交互来修改其行为、报告其历史或将本地信息传达给全球生物系统。细菌或哺乳动物细胞中的生物记忆可用于监测人的微生物组，开发对环境做出反应的智能材料，或创建对活细胞本身所需的生物毒素做出反应的专门传感器。受控的这种环境不仅确保了它们的长期生存和生存能力，而且还允许对内存进行受控读写。读写最终将成为这些系统的“编程”方式以及它们收集的数据的作用方式。该项目使用移动少量液体的设备（微流体）创建新颖的生物记忆，用于并行测试许多生物记忆配置，以确定哪些最适合测试特定环境信号（例如毒素、金属、然后将这些最好的存储器与低成本的嵌入式电子设备集成，这些电子设备可以读取其输出并控制容纳存储器的微流体环境，并允许外部信号在存储器中“写入”信息。和电子学一起形成所谓的“混合生物电子微流体存储阵列”，这些设备将探索众多跨学科挑战，并为探索计算机科学、合成生物学和材料科学领域的应用创造机会。为了最大限度地发挥该项目的影响，包括微流体和电子设计和软件在内的所有研究都将开源，所有遗传记忆元件将在项目期间通过 NSF 资助向科学界提供指导。该项目具有三个阶段的结构，其中第一阶段是在高通量、电子增强的微流体筛选平台的帮助下开发生物记忆。 DNA 将充当不可逆记忆，而表观遗传、染色质修饰将充当可逆机制。此阶段将涉及创建 1000 个潜在记忆元素，在第二阶段中，第一阶段中的最佳候选元素将被大规模并行组合。高度集成的微流控平台，用于开发最终部署的微流控以及建立存储器所需的操作和控制条件。最后，在第三阶段，创建一个小规模部署环境来观察和调整微流控的性能。在水生部署场景中新创建的混合生物电子微流体存储阵列旨在复制现实世界中重金属和其他环境信号的生物传感应用，这些阶段明确解决了三个生物存储挑战（创建、控制和部署）。最先进的生物可逆和不可逆存储器、液滴微流体和定制的嵌入式半导体电子产品。该奖项是 NSF 的法定使命，通过使用基金会的智力价值和更广泛的影响审查标准。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

High-throughput continuous evolution of compact Cas9 variants targeting single-nucleotide-pyrimidine PAMs.

DOI：
10.1038/s41587-022-01410-2
发表时间：
2023-01
期刊：
NATURE BIOTECHNOLOGY
影响因子：
46.9
作者：
Huang, Tony P.;Heins, Zachary J.;Miller, Shannon M.;Wong, Brandon G.;Balivada, Pallavi A.;Wang, Tina;Khalil, Ahmad S.;Liu, David R.
通讯作者：
Liu, David R.

Machine learning for microfluidic design and control.