Versatile and Programmable DNA Logic Gates on Universal and Label-Free Homogeneous Electrochemical Platform.

Herein, a novel universal and label-free homogeneous electrochemical platform is demonstrated, on which a complete set of DNA-based two-input Boolean logic gates (OR, NAND, AND, NOR, INHIBIT, IMPLICATION, XOR, and XNOR) is constructed by simply and rationally deploying the designed DNA polymerization/nicking machines without complicated sequence modulation. Single-stranded DNA is employed as the proof-of-concept target/input to initiate or prevent the DNA polymerization/nicking cyclic reactions on these DNA machines to synthesize numerous intact G-quadruplex sequences or binary G-quadruplex subunits as the output. The generated output strands then self-assemble into G-quadruplexes that render remarkable decrease to the diffusion current response of methylene blue and, thus, provide the amplified homogeneous electrochemical readout signal not only for the logic gate operations but also for the ultrasensitive detection of the target/input. This system represents the first example of homogeneous electrochemical logic operation. Importantly, the proposed homogeneous electrochemical logic gates possess the input/output homogeneity and share a constant output threshold value. Moreover, the modular design of DNA polymerization/nicking machines enables the adaptation of these homogeneous electrochemical logic gates to various input and output sequences. The results of this study demonstrate the versatility and universality of the label-free homogeneous electrochemical platform in the design of biomolecular logic gates and provide a potential platform for the further development of large-scale DNA-based biocomputing circuits and advanced biosensors for multiple molecular targets.

[1]  I. Hsing,et al.  Electrochemical Interrogation of Kinetically-Controlled Dendritic DNA/PNA Assembly for Immobilization-Free and Enzyme-Free Nucleic Acids Sensing. , 2015, ACS nano.

[2]  E. Wang,et al.  G-quadruplex DNAzyme based molecular catalytic beacon for label-free colorimetric logic gates. , 2011, Biomaterials.

[3]  Shana Topp,et al.  Emerging applications of riboswitches in chemical biology. , 2010, ACS chemical biology.

[4]  Ruijie Deng,et al.  Multiresponsive rolling circle amplification for DNA logic gates mediated by endonuclease. , 2014, Analytical chemistry.

[5]  Li Wang,et al.  Graphene-based aptamer logic gates and their application to multiplex detection. , 2012, ACS nano.

[6]  Ting Hou,et al.  Label-Free and Enzyme-Free Homogeneous Electrochemical Biosensing Strategy Based on Hybridization Chain Reaction: A Facile, Sensitive, and Highly Specific MicroRNA Assay. , 2015, Analytical chemistry.

[7]  I. Willner,et al.  From cascaded catalytic nucleic acids to enzyme-DNA nanostructures: controlling reactivity, sensing, logic operations, and assembly of complex structures. , 2014, Chemical reviews.

[8]  Cuichen Wu,et al.  Nucleic acid based logical systems. , 2014, Chemistry.

[9]  Ming Zhou,et al.  Bioelectrochemical interface engineering: toward the fabrication of electrochemical biosensors, biofuel cells, and self-powered logic biosensors. , 2011, Accounts of chemical research.

[10]  Ming Zhou,et al.  A self-powered and reusable biocomputing security keypad lock system based on biofuel cells. , 2010, Chemistry.

[11]  I. Hsing,et al.  Conformation-dependent exonuclease III activity mediated by metal ions reshuffling on thymine-rich DNA duplexes for an ultrasensitive electrochemical method for Hg2+ detection. , 2013, Analytical chemistry.

[12]  G. Ruiter,et al.  Surface-confined assemblies and polymers for molecular logic. , 2011 .

[13]  Xuemei Li,et al.  Multiplexed sensing of mercury(II) and silver(I) ions: a new class of DNA electrochemiluminescent-molecular logic gates. , 2011, Biosensors & bioelectronics.

[14]  Huangxian Ju,et al.  Target-driven DNA association to initiate cyclic assembly of hairpins for biosensing and logic gate operation† †Electronic supplementary information (ESI) available: Supplementary table and figures. See DOI: 10.1039/c5sc01215e Click here for additional data file. , 2015, Chemical science.

[15]  Yinglin Zhou,et al.  Methylene blue as a G-quadruplex binding probe for label-free homogeneous electrochemical biosensing. , 2014, Analytical chemistry.

[16]  Longhua Guo,et al.  DNA methylation detection and inhibitor screening based on the discrimination of the aggregation of long and short DNA on a negatively charged indium tin oxide microelectrode. , 2014, Analytical chemistry.

[17]  Muzi Chen,et al.  DNA-programmed dynamic assembly of quantum dots for molecular computation. , 2014, Angewandte Chemie.

[18]  Yong Xia,et al.  DNA-based visual majority logic gate with one-vote veto function , 2015, Chemical science.

[19]  Ying Zhu,et al.  A RET-supported logic gate combinatorial library to enable modeling and implementation of intelligent logic functions , 2015, Chemical science.

[20]  Hongyun Liu,et al.  Biomacromolecular Logic Devices Based on Simultaneous Electrocatalytic and Electrochemiluminescence Responses of Ru(bpy)32+ at Molecularly Imprinted Polymer Film Electrodes , 2015 .

[21]  Jing Yang,et al.  DNAzyme-Based Logic Gate-Mediated DNA Self-Assembly. , 2015, Nano letters.

[22]  Zhenyu Lin,et al.  Exonuclease-Catalyzed Target Recycling Amplification and Immobilization-free Electrochemical Aptasensor. , 2015, Analytical chemistry.

[23]  Dik-Lung Ma,et al.  Simple DNA-based logic gates responding to biomolecules and metal ions , 2013 .

[24]  Christopher A. Voigt,et al.  Genetic programs constructed from layered logic gates in single cells , 2012, Nature.

[25]  X. Qu,et al.  Using thermally regenerable cerium oxide nanoparticles in biocomputing to perform label-free, resettable, and colorimetric logic operations. , 2012, Angewandte Chemie.

[26]  Li Wang,et al.  Exonuclease III-aided autocatalytic DNA biosensing platform for immobilization-free and ultrasensitive electrochemical detection of nucleic acid and protein. , 2014, Analytical chemistry.

[27]  Shaojun Dong,et al.  Four-way junction-driven DNA strand displacement and its application in building majority logic circuit. , 2013, ACS nano.

[28]  A. P. de Silva,et al.  Molecular logic and computing. , 2007, Nature nanotechnology.

[29]  Sai Bi,et al.  Metal ions triggered ligase activity for rolling circle amplification and its application in molecular logic gate operations , 2013 .

[30]  An omega-like DNA nanostructure utilized for small molecule introduction to stimulate formation of DNAzyme-aptamer conjugates. , 2014, Chemical communications.

[31]  Wei Zhai,et al.  A series of logic gates based on electrochemical reduction of Pb2+ in self-assembled G-quadruplex on the gold electrode. , 2014, Chemical communications.

[32]  Richard M Crooks,et al.  Design and operation of microelectrochemical gates and integrated circuits. , 2010, Journal of the American Chemical Society.

[33]  Françoise Remacle,et al.  Logic reversibility and thermodynamic irreversibility demonstrated by DNAzyme-based Toffoli and Fredkin logic gates , 2012, Proceedings of the National Academy of Sciences.

[34]  Sai Bi,et al.  Target-triggered cascade recycling amplification for label-free detection of microRNA and molecular logic operations. , 2016, Chemical communications.

[35]  Penghui Zhang,et al.  In situ amplification of intracellular microRNA with MNAzyme nanodevices for multiplexed imaging, logic operation, and controlled drug release. , 2015, ACS nano.

[36]  Hua Cui,et al.  Chemiluminescent logic gates based on functionalized gold nanoparticles/graphene oxide nanocomposites. , 2013, Chemistry.

[37]  Xiaogang Qu,et al.  Combination of Graphene Oxide and Thiol‐Activated DNA Metallization for Sensitive Fluorescence Turn‐On Detection of Cysteine and Their Use for Logic Gate Operations , 2011 .

[38]  Bingling Li,et al.  DNA detection using origami paper analytical devices. , 2013, Analytical chemistry.

[39]  Weihong Tan,et al.  Programmable and Multiparameter DNA-Based Logic Platform For Cancer Recognition and Targeted Therapy , 2014, Journal of the American Chemical Society.

[40]  Tao Li,et al.  Enzyme‐Free Unlabeled DNA Logic Circuits Based on Toehold‐Mediated Strand Displacement and Split G‐Quadruplex Enhanced Fluorescence , 2013, Advanced materials.

[41]  Andreas Offenhäusser,et al.  An electrochemically transduced XOR logic gate at the molecular level. , 2010, Angewandte Chemie.

[42]  Itamar Willner,et al.  DNAzymes for sensing, nanobiotechnology and logic gate applications. , 2008, Chemical Society reviews.

[43]  Yan Du,et al.  Aptamer-controlled biofuel cells in logic systems and used as self-powered and intelligent logic aptasensors. , 2010, Journal of the American Chemical Society.

[44]  Vladimir Privman,et al.  Enzyme-based logic systems for information processing. , 2009, Chemical Society reviews.

[45]  Shaojun Dong,et al.  Aptamer-based sensing platform using three-way DNA junction-driven strand displacement and its application in DNA logic circuit. , 2014, Analytical chemistry.

[46]  Lingwen Zeng,et al.  Computational lateral flow biosensor for proteins and small molecules: a new class of strip logic gates. , 2012, Analytical chemistry.

[47]  Knut Rurack,et al.  An ionically driven molecular IMPLICATION gate operating in fluorescence mode. , 2007, Chemistry.

[48]  Xiaogang Qu,et al.  Nucleic Acids and Smart Materials: Advanced Building Blocks for Logic Systems , 2014, Advanced materials.

[49]  Lei Ge,et al.  Affinity-Mediated Homogeneous Electrochemical Aptasensor on a Graphene Platform for Ultrasensitive Biomolecule Detection via Exonuclease-Assisted Target-Analog Recycling Amplification. , 2016, Analytical chemistry.

[50]  Li Zhang,et al.  Easy design of colorimetric logic gates based on nonnatural base pairing and controlled assembly of gold nanoparticles. , 2013, Langmuir : the ACS journal of surfaces and colloids.

[51]  Zhenyu Lin,et al.  Ultraselective homogeneous electrochemical biosensor for DNA species related to oral cancer based on nicking endonuclease assisted target recycling amplification. , 2015, Analytical chemistry.

[52]  Cuichen Wu,et al.  A logical molecular circuit for programmable and autonomous regulation of protein activity using DNA aptamer-protein interactions. , 2012, Journal of the American Chemical Society.

[53]  Junlin Wen,et al.  Concatenated logic circuits based on a three-way DNA junction: a keypad-lock security system with visible readout and an automatic reset function. , 2014, Angewandte Chemie.

[54]  Danke Xu,et al.  Disposable electrochemical aptasensor array by using in situ DNA hybridization inducing silver nanoparticles aggregate for signal amplification. , 2014, Analytical chemistry.

[55]  Genxi Li,et al.  A set of logic gates fabricated with G-quadruplex assembled at an electrode surface. , 2012, Chemical communications.

[56]  Uwe Pischel,et al.  Chemical approaches to molecular logic elements for addition and subtraction. , 2007, Angewandte Chemie.