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

记录事件的能力（“记忆”）是许多复杂系统的关键部分。记录事件允许这些系统根据先前的交互修改其行为，报告其历史记录，或将本地信息传达给全球社区。生物系统将大大受益于记忆元素的创造。细菌或哺乳动物细胞中的生物记忆可用于监测人体的微生物组，开发对环境做出反应的智能材料，或创建对生物毒素做出反应的专门传感器。活细胞中的生物记忆本身需要一个受控的环境。这种环境不仅确保了它们的长期生存和活力，而且还允许对存储器进行受控的阅读和写入。阅读和写最终将是这些系统如何“编程”，以及如何对它们收集的数据采取行动。该项目使用移动少量液体的设备（微流体）创建新的生物记忆。微流体技术用于并行测试许多生物记忆配置，以确定哪些是最好的测试特定环境信号（例如毒素，金属，激素）。这些存储器中最好的存储器然后与低成本的嵌入式电子设备集成，这些电子设备可以读取它们的输出，以及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。生物存储器、微流体和电子器件一起形成了所谓的“混合生物电子微流体存储器阵列”。这些设备将探索许多跨学科的挑战，并为探索计算机科学，合成生物学和材料科学边界的应用创造机会。 为了最大限度地发挥该项目的影响力，包括微流体和电子设计和软件在内的所有研究都将开源。所有遗传记忆元素将提供给科学界。超过48名本科生将在项目期间通过NSF赞助的项目和波士顿大学的夏季研究项目进行指导。该项目有一个三阶段的结构，在第一阶段，生物记忆是在高通量，电子增强微流体筛选平台的帮助下开发的。DNA上的酶促反应将充当不可逆记忆，而表观遗传、染色质修饰将充当可逆机制。这一阶段将涉及创建1000个潜在的存储元件。在第二阶段中，来自第一阶段的顶级候选人在大规模并行，高度集成的微流体平台中组合，以开发最终部署的微流体，并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，以观察和调整新创建的混合生物电子微流体存储器阵列在水生部署场景中的性能，旨在复制重金属和其他环境信号的真实生物传感应用。这些阶段明确地解决了三个生物记忆挑战（创建、控制和部署），使用最先进的生物可逆和不可逆记忆、液滴微流体和定制的嵌入式微流控器为基础的电子产品。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.