Programmable DNA Nanoindicator‐Based Platform for Large‐Scale Square Root Logic Biocomputing

Abstract The prospect of programming molecular computing systems to realize complex autonomous tasks has advanced the design of synthetic biochemical logic circuits. One way to implement digital and analog integrated circuits is to use noncovalent hybridization and strand displacement reactions in cell‐free and enzyme‐free nucleic acid systems. To date, DNA‐based circuits involving tens of logic gates capable of implementing basic and complex logic functions have been demonstrated experimentally. However, most of these circuits are still incapable of realizing complex mathematical operations, such as square root logic operations, which can only be carried out with 4 bit binary numbers. A high‐capacity DNA biocomputing system is demonstrated through the development of a 10 bit square root logic circuit. It can calculate the square root of a 10 bit binary number (within the decimal integer 900) by designing DNA sequences and programming DNA strand displacement reactions. The input signals are optimized through the output feedback to improve performance in more complex logical operations. This study provides a more universal approach for applications in biotechnology and bioengineering.