Manufacturing Reusable NAND Logic Gates and Their Initial Circuits for DNA Nanoprocessors

Abstract

DNA‐based computers can potentially analyze complex sets of biological markers, thereby advancing diagnostics and the treatment of diseases. Despite extensive efforts, DNA processors have not yet been developed due, in part, to limitations in the ability to integrate available logic gates into circuits. We have designed a NAND gate, which is one of the functionally complete set of logic connectives. The gate's design avoids stem‐loop‐folded DNA fragments, and is capable of reusable operations in RNase H‐containing buffer. The output of the gate can be translated into RNA‐cleaving activity or a fluorescent signal produced either by a deoxyribozyme or a molecular beacon probe. Furthermore, three NAND‐gate‐forming DNA strands were crosslinked by click chemistry and purified in a simple procedure that allowed ≈1013 gates to be manufactured in 16 h, with a hands‐on time of about 30 min. Two NAND gates can be joined into one association that performs a new logic function simply by adding a DNA linker strand. Approaches developed in this work could contribute to the development of biocompatible DNA logic circuits for biotechnological and medical applications.

Realization of multi-configurable logic gate behaviour on fluorescence switching signalling of naphthalene diimide congeners

“… 29 Likewise, the molecular logic gates 30,31 also fulfil Boolean algebra by acquiring chemical, optical or biological inputs and accordingly produce a single output. 32,33 This offers a new paradigm shift for future computing technology that facilitates with increasing functionality, reducing in size and cutting in cost. In recent decades, many biological and chemical systems have displayed the feasibility to effectuate various Boolean logic operations such as AND, YES, NOT, OR, NAND, IMPLICATION (IMPLY), INHIBIT (INHIB), XOR, XNOR, etc.…”

DNA Logic Gates Integrated on DNA Substrates in Molecular Computing

“…Input 1 binds to Bridge 1, however, Bridge 2 keeps the catalytic core integrity, vice versa if input 2 is added. When Bridge 1 and Bridge 2 are bound to Input 1 and Input 2, the catalytic core falls apart into Dza and Dzb fragments inhibiting substrate cleavage (Two input scheme), redrawn from ref [49]. e) Boolean truth tables dictating the output for all possible inputs for YES, NOT, OR and NAND Boolean logic.…”

“…This was possibly due to the torsional effects and rigidity conferred from the multiple crossover points (Figure 2d and Figure 3d). [49,77] Another proposed alternative is using 3D DNA substrates [10,11,78,79] which we discuss in section 4.…”

DNA Matrix Operation Based on the Mechanism of the DNAzyme Binding to Auxiliary Strands to Cleave the Substrate

“…Notably, catalytic nucleic acids (DNAzymes or ribozymes) [ 30 , 31 ] have had prominent applications in logic calculation [ 32 , 33 , 34 , 35 ], micromolecular detection (virus, miRNA) [ 36 ], biosensors [ 37 , 38 , 39 ], and signal amplification [ 40 ] in recent years because of their characteristics of specific recognition and high-efficiency catalysis. The DNAzyme is an enzyme that relies on and is affected by metal ions.…”