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

University Of New Mexico, Albuquerque NM

Investigators

Abstract

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.