SemiSynBio-II: A Hybrid Programmable Nano-Bioelectronic System

活细胞配备了高度通用的内置工具箱，包括DNA、RNA和蛋白质，用于分子通信、计算、存储和对环境刺激的感知/激活。合成生物学已经成功地通过利用具有增强的自然功能或新的人类定义功能的相同的生物工具包来开发工程细胞。这些工程细胞可以潜在地作为生物前端层，与环境自然对接，并作为生物传感器/执行器、分子计算平台和分子存储器，为环境监测和医疗保健等许多全球挑战提供革命性的解决方案。与此同时，随着几十年的技术进步，半导体技术，如互补金属氧化物半导体集成电路(IC)，正被广泛用作半导体后端层，以实现各种集成、通信和计算能力。该项目研究了混合可编程纳米生物电子系统的开发，作为第一个概念验证演示，该系统既利用了工程细菌作为“生物前端”的精致合成功能，也利用了作为“半导体后端”的超低功耗cmos集成电路芯片的全部功能。这种系统的目标应用包括用于环境监测的现场生物传感器。该项目有可能对基础科学、教育和技术产生长期和更广泛的影响。它带来了合成生物学、混合生物电子学、集成电路/封装、信息理论和计算方面的专业知识。该项目直接涉及征集的三个研究主题：主题1，生物分子存储器和计算；主题2，生物和半导体的接口；主题4，混合半导体-生物微电子系统。它寻求促进产业界和学术界之间的合作，从而促进技术转让。调查小组将培训佐治亚理工学院和麻省理工学院的研究生和本科生，包括少数族裔和代表性不足的学生。该项目还将强调K-12外联活动，以促进当地少数民族高中生的教育。特别是，研究团队将招聘高中教师实习生，以加强他们的课程，并为K-12学生组织实验室之旅。研究成果将通过高影响力的期刊、主要会议、网站和社交媒体传播，并将被整合到佐治亚理工学院和麻省理工学院的多门相关课程中。该项目旨在推动科学在多个领域的发展，并开发一种集成的混合可编程纳米生物电子系统。在这样的系统中，各种细菌菌株被设计为传感、存储和计算生物前沿，以(1)执行广谱化学传感，例如用于环境监测的重金属检测，(2)在细菌内提供基于DNA的模拟/数字信息存储，(3)通过随机计算执行分子计算并对用于DNA存储的信号进行编码，以及(4)通过外部光和电刺激支持细菌传感器的“可变增益”重新编程。作为集成半导体电子后端，将开发具有片上像素化大规模并行阵列的CMOSIC芯片，以提供与细菌前端的双向多模式接口，即从细菌读取存储的感觉信息，并写入控制信号以对细菌传感器进行重新编程。细菌菌株和CMOSIC将被集成在3D打印的微流控结构中，并带有单独的腔室。建议的组件和系统将通过使用佐治亚理工学院和麻省理工学院的资源进行体外实验来演示。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

Living cells are equipped with highly versatile built-in toolkits of DNA, RNA, and proteins for molecular communication, computing, storage, and sensing/actuation in response to environmental stimuli. Synthetic biology has been successful in developing engineered cells by harnessing the same biological toolkits with enhanced natural functions or new human-defined functions. These engineered cells can potentially serve as a biological frontend layer that naturally interfaces with the environment and acts as biosensors/actuators, molecular computing platforms, and molecular memory to provide revolutionary solutions for many global challenges such as environmental monitoring, and healthcare. In parallel, with decades of technological advances, semiconductor technologies, e.g., Complementary-Metal-Oxide-Semiconductor (CMOS) integrated circuits (ICs), are being widely employed as a semiconductor backend layer to achieve various integration, communication, and computation capabilities. This project investigates the development of a hybrid programmable nano-bioelectronic system as a first proof-of-concept demonstration that harnesses both the exquisite synthetic functionalities of engineered bacteria as the "biological frontend" and the full functionalities of the ultra-low-power CMOS integrated circuit chips as the "semiconductor backend." The target application of such a system includes in-field biological sensor for environment monitoring. The project has potentials for long-term broader impacts on basic science, education, and technology. It brings expertise from synthetic biology, hybrid bioelectronics, integrated circuits/packaging, information theory, and computing. The project directly addresses three research themes of the solicitation: Theme-1, biomolecular memory and computation; Theme 2, interface of biology and semiconductors; Theme-4, hybrid semiconductor-biological microelectronic systems. It seeks to foster collaborations between industry and academia and hence facilitates technology transfer. The team of investigators will train graduate and undergraduate students at Georgia Tech and MIT, including minority and under-represented students. The project will also emphasize K-12 outreach to promote education of local minority high school students. In particular, the research team will recruit high school teacher interns to enhance their curricula and organize lab tours for K-12 students. The research results will be disseminated through high-impact journals, premier conferences, websites, and social media, and will be integrated into multiple related courses at Georgia Tech and MIT.The project aims to advance the science in multiple fronts and develop an integrated hybrid programmable nano-bioelectronic system. In such a system, a variety of bacteria strains are engineered as sensing, storage, and computation biological frontends to (1) perform wide-spectrum chemical sensing, e.g., heavy metal detections for environmental monitoring, (2) provide in-bacteria DNA-based storage of analog/digital information, (3) execute molecular computation via stochastic computing and encode the signal for the DNA storage, and (4) support "variable gain" reprogramming of bacteria sensors by external optical and electrical stimuli. As the integrated semiconductor electronics backend, CMOS IC chips with on-chip pixelated massively paralleled arrays will be developed to provide two-way multi-modal interfaces with the bacteria frontends, i.e., for reading stored sensory information from the bacteria and writing control signals to reprogram the bacteria sensors. The bacteria strains and CMOS ICs will be integrated together in 3D-printed microfluidics structures and packages with separate chambers. The proposed components and systems will be demonstrated through in vitro experiments using the resources at Georgia Tech and MIT.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.