AF: SHF: Small: Compartmentalized circuit architectures for real-world biocomputing applications

AF：SHF：小型：适用于实际生物计算应用的分隔电路架构

• 批准号: 1318833
• 负责人: Darko Stefanovic
• 金额: $ 48万
• 依托单位: University of New Mexico
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-15 至 2017-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1318833&HistoricalAwards=false
• 关键词: AF; SHF; Small; Compartmentalized; circuit

In recent years there have been great advances in nucleic acid technology, such as the development of biomolecular circuits that compute logic functions, mimicking the behavior of semiconductor circuits. Biomolecular logic circuits consist of DNA or RNA molecules that react with each other and with particular target molecules. The goal of the circuit is to detect whether the target molecules are present and decide on an appropriate response. For example, a biomolecular logic circuit might instruct a particular cell to self-destruct, if that cell contains particular molecules known to indicate cancer.Because molecules are continually colliding with each other, special care must be taken when designing biomolecular logic circuits to ensure that only the desired reactions actually take place. As circuits grow in size and complexity, it will become increasingly difficult to prevent unwanted reactions between different molecules within the circuit. In real-world applications we must also guard against interference caused by unwanted reactions with other molecules that are present in the solution but are not part of the circuit. Unwanted reactions introduce noise into the system, preventing the circuit from computing reliably.This project will tackle these challenges by designing biomolecular logic circuits using distributed computational modules that are physically separated, to reduce non-specific molecular interactions. Each module will contain specific computing components inside a lipid membrane, and collections of communicating modules will be designed to carry out distributed computations. Putting modules inside membranes will reduce unwanted reactions between different parts of the circuit, which will increase the reliability of the system. It will also enable identical DNA sequences to be reused within multiple modules, which is an important step towards standardization of biomolecular computing components. Standardization will make it easier to build larger and more sophisticated circuits that are capable of more complex decision-making.Intellectual Merit: The project will develop new designs for biomolecular logic circuits based on distributed, communicating modules, and investigate the advantages of this approaches to molecular computing, for example in terms of reliability. These advances will be directly applicable to many biomedical problems of interest, including detection of viruses and the development of autonomous smart drugs.Broader Impact: The project will have a broad impact on medical technology by developing a new biocompatible platform for the implementation of biomolecular logic circuits for medical applications. This will improve access to rapid diagnoses, particularly in underserved communities. Community outreach in New Mexico will be achieved via internship programs, enabling high school and undergraduate students to experience interdisciplinary scientific research.

近年来，核酸技术取得了巨大的进步，例如模拟半导体电路行为的计算逻辑功能的生物分子电路的发展。生物分子逻辑电路由DNA或RNA分子组成，它们相互作用，并与特定的靶分子发生反应。该电路的目的是检测目标分子是否存在，并决定适当的反应。例如，一个生物分子逻辑电路可能会指示一个特定的细胞自我毁灭，如果这个细胞含有已知的表明癌症的特定分子。由于分子之间不断发生碰撞，因此在设计生物分子逻辑电路时必须特别小心，以确保只发生期望的反应。随着电路的尺寸和复杂性的增加，防止电路中不同分子之间发生不必要的反应将变得越来越困难。在实际应用中，我们还必须防止与溶液中存在但不属于电路的其他分子发生不必要的反应所引起的干扰。不必要的反应将噪声引入系统，使电路无法可靠地计算。该项目将通过使用物理分离的分布式计算模块设计生物分子逻辑电路来解决这些挑战，以减少非特异性分子相互作用。每个模块将在脂膜内包含特定的计算组件，通信模块的集合将被设计用于执行分布式计算。将模块放入膜内将减少电路不同部分之间不必要的反应，这将增加系统的可靠性。它还将使相同的DNA序列能够在多个模块中重复使用，这是迈向生物分子计算组件标准化的重要一步。标准化将使制造更大、更复杂的电路变得更容易，从而能够做出更复杂的决策。智力优势：该项目将开发基于分布式通信模块的生物分子逻辑电路的新设计，并研究这种方法在分子计算方面的优势，例如在可靠性方面。这些进步将直接适用于许多感兴趣的生物医学问题，包括病毒检测和自主智能药物的开发。更广泛的影响：该项目将对医疗技术产生广泛的影响，为医疗应用的生物分子逻辑电路的实施开发一个新的生物相容性平台。这将改善获得快速诊断的机会，特别是在服务不足的社区。新墨西哥州的社区外展将通过实习项目实现，使高中生和本科生能够体验跨学科的科学研究。