CCF:SHF:Small:NAND gate based integrated DNA circuits

CCF:SHF:Small：基于与非门的集成 DNA 电路

• 批准号: 2226021
• 负责人: Dmitry Kolpashchikov
• 金额: $ 36.3万
• 依托单位: The University of Central Florida Board of Trustees
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-10-01 至 2025-09-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2226021&HistoricalAwards=false
• 关键词: CCF; SHF; Small; NAND; gate

This project is devoted to addressing existing technological challenges toward building a computer made of DNA. Electronic computers have dramatically improved information processing speed and ultimately promoted progress in science, education, technologies, and welfare. However, modern electronic computers are difficult to use inside human bodies as they are made of non-biocompatible and non-biodegradable materials. Moreover, electronic computers can not directly recognize chemical inputs (e.g., proteins, hormones, DNA, and RNA) and require chemical sensors with capabilities to translate the chemical recognition event into an electronic signal. On the other hand, computers do not have to be electronic. For example, some early computers used mechanical movements of their components as input/output signals. Biomedical applications would benefit if computers were made of biological molecules. Such computers could be used as components of molecular biorobots to continuously control the health state of a human body without human assistance. In addition, they could be used in personalized medicine to analyze complex mixtures of biological markers, thus improving health care in the nation. The principles of the DNA nano-processor developed in this project can impact the biomedical field by providing efficient tools for monitoring and correcting a disease state. The concepts and experimental approaches used in this project will be incorporated into undergraduate and graduate education.The Project Investigator's long-term goal is to construct a molecular scale processor from DNA logic gates. This project includes the following stages needed for building a DNA nano-processor. First, principles for integrating DNA logic gates in DNA circuits will be developed. Second, principles of connecting two integrated circuits in a more complex circuit will be established to enable modular and scalable construction of complex DNA circuits. Third, a universal mechanism for powering the integrated DNA circuits via signal amplification will be developed. Finally, the developed technologies will be applied to assemble complex computational circuits made of DNA molecules. Therefore, this project will solve the problems of DNA logic gate integration and powering. The solution to these problems will create a basis for manufacturing a DNA computer, a smaller and biocompatible counterpart of the modern silicon processors. The research activities will be integrated with education via (i) developing biochemistry wet lab experiments dealing with the integration of DNA logic gates and their application in molecular diagnostics; (ii) research training of students at undergraduate and graduate levels; (iii) outreach program. The outreach activity has the potential to impact high school students across multi-ethnic Central Florida through partnerships with local high schools.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.

该项目致力于解决构建 DNA 计算机的现有技术挑战。电子计算机极大地提高了信息处理速度，最终促进了科学、教育、技术和福利的进步。然而，现代电子计算机很难在人体内使用，因为它们是由非生物相容性和不可生物降解的材料制成的。此外，电子计算机无法直接识别化学输入（例如蛋白质、激素、DNA 和 RNA），需要化学传感器能够将化学识别事件转化为电子信号。另一方面，计算机不一定是电子的。例如，一些早期的计算机使用其组件的机械运动作为输入/输出信号。如果计算机是由生物分子制成的，生物医学应用将会受益。这种计算机可以用作分子生物机器人的组件，在没有人类帮助的情况下持续控制人体的健康状态。此外，它们还可以用于个性化医疗来分析生物标记的复杂混合物，从而改善国家的医疗保健。该项目开发的 DNA 纳米处理器的原理可以通过提供监测和纠正疾病状态的有效工具来影响生物医学领域。 该项目中使用的概念和实验方法将纳入本科生和研究生教育。项目研究者的长期目标是从 DNA 逻辑门构建分子级处理器。该项目包括构建 DNA 纳米处理器所需的以下阶段。首先，将制定在 DNA 电路中集成 DNA 逻辑门的原理。 其次，将建立在更复杂的电路中连接两个集成电路的原理，以实现复杂 DNA 电路的模块化和可扩展构建。第三，将开发一种通过信号放大为集成DNA电路供电的通用机制。最后，所开发的技术将应用于组装由 DNA 分子组成的复杂计算电路。因此，该项目将解决DNA逻辑门集成和供电的问题。这些问题的解决将为制造 DNA 计算机奠定基础，DNA 计算机是现代硅处理器的更小且具有生物兼容性的对应物。研究活动将通过以下方式与教育相结合：(i) 开发涉及 DNA 逻辑门集成及其在分子诊断中应用的生物化学湿实验室实验； (ii) 本科生和研究生的研究培训； (三) 外展计划。通过与当地高中的合作，外展活动有可能影响佛罗里达州中部多种族的高中生。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力优点和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

OWL2: a molecular beacon-based nanostructure for highly selective detection of single-nucleotide variations in folded nucleic acids

OWL2：一种基于分子信标的纳米结构，用于高选择性检测折叠核酸中的单核苷酸变异

• DOI: 10.1039/d2nr05590b
• 发表时间: 2023-03
• 期刊: Nanoscale
• 影响因子: 6.7
• 作者: Mueller, Brittany L.;Liberman, Mark J.;Kolpashchikov, Dmitry M.
• 通讯作者: Kolpashchikov, Dmitry M.