A Novel Bio-Sensor Based on DNA Strand Displacement

DNA strand displacement technology performs well in sensing and programming DNA segments. In this work, we construct DNA molecular systems based on DNA strand displacement performing computation of logic gates. Specifically, a class of so-called “DNA neurons” are achieved, in which a “smart” way inspired by biological neurons encoding information is developed to encode and deliver information using DNA molecules. The “DNA neuron” is bistable, that is, it can sense DNA molecules as input signals, and release “negative” or “positive” signals DNA molecules. We design intelligent DNA molecular systems that are constructed by cascading some particularly organized “DNA neurons”, which could perform logic computation, including AND, OR, XOR logic gates, automatically. Both simulation results using visual DSD (DNA strand displacement) software and experimental results are obtained, which shows that the proposed systems can detect DNA signals with high sensitivity and accretion; moreover, the systems can process input signals automatically with complex nonlinear logic. The method proposed in this work may provide a new way to construct a sensitive molecular signal detection system with neurons spiking behavior in vitro, and can be used to develop intelligent molecular processing systems in vivo.

[1]  Linqiang Pan,et al.  General DNA Automaton Model with R/W Tape , 2006, ICIC.

[2]  Lulu Qian,et al.  Supporting Online Material Materials and Methods Figs. S1 to S6 Tables S1 to S4 References and Notes Scaling up Digital Circuit Computation with Dna Strand Displacement Cascades , 2022 .

[3]  T. Scheetz,et al.  Novel Molecular and Computational Methods Improve the Accuracy of Insertion Site Analysis in Sleeping Beauty-Induced Tumors , 2011, PloS one.

[4]  Alan E. Rowan,et al.  Helical Molecular Programming , 1998 .

[5]  M. Egholm,et al.  Sequence-selective recognition of DNA by strand displacement with a thymine-substituted polyamide. , 1991, Science.

[6]  N. Seeman,et al.  Design and self-assembly of two-dimensional DNA crystals , 1998, Nature.

[7]  Thomas H. LaBean,et al.  Constructing novel materials with DNA , 2007 .

[8]  E. Winfree,et al.  Algorithmic Self-Assembly of DNA Sierpinski Triangles , 2004, PLoS biology.

[9]  T. LaBean,et al.  Self-assembling DNA templates for programmed artificial biomineralization , 2011 .

[10]  Robert R. Birge,et al.  Volumetric optical memory based on bacteriorhodopsin , 2002 .

[11]  Andrew W. Eckford,et al.  Tabletop Molecular Communication: Text Messages through Chemical Signals , 2013, PloS one.

[12]  Luca Cardelli,et al.  A programming language for composable DNA circuits , 2009, Journal of The Royal Society Interface.

[13]  Andrew J. Turberfield,et al.  Kinetically controlled self-assembly of DNA oligomers. , 2009, Journal of the American Chemical Society.

[14]  E. Shapiro,et al.  Programmable and autonomous computing machine made of biomolecules , 2001, Nature.

[15]  Gheorghe Paun,et al.  The Oxford Handbook of Membrane Computing , 2010 .

[16]  G. Seelig,et al.  Dynamic DNA nanotechnology using strand-displacement reactions. , 2011, Nature chemistry.

[17]  Brian G. Scrivens,et al.  Strand displacement amplification and homogeneous real-time detection incorporated in a second-generation DNA probe system, BDProbeTecET. , 1999, Clinical chemistry.

[18]  L M Adleman,et al.  Molecular computation of solutions to combinatorial problems. , 1994, Science.

[19]  Gheorghe Paun,et al.  Membrane Computing , 2002, Natural Computing Series.

[20]  Riccardo Poli,et al.  Exact Schema Theory and Markov Chain Models for Genetic Programming and Variable-length Genetic Algorithms with Homologous Crossover , 2004, Genetic Programming and Evolvable Machines.

[21]  Jin Xu,et al.  Improve Capability of DNA Automaton: DNA Automaton with Three Internal States and Tape Head Move in Two Directions , 2005, ICIC.

[22]  T. LaBean,et al.  Connecting the nanodots: programmable nanofabrication of fused metal shapes on DNA templates. , 2011, Nano letters.

[23]  G. Walker,et al.  Strand displacement amplification--an isothermal, in vitro DNA amplification technique. , 1992, Nucleic acids research.

[24]  Norbert Hampp,et al.  Bacteriorhodopsin as a Photochromic Retinal Protein for Optical Memories. , 2000, Chemical reviews.

[25]  Martin Zacharias,et al.  ATTRACT-EM: A New Method for the Computational Assembly of Large Molecular Machines Using Cryo-EM Maps , 2012, PloS one.

[26]  Guangzhao Cui,et al.  DNA Self-Assembly for Graph Vertex 3-Coloring Problem , 2012 .

[27]  G. Seelig,et al.  Enzyme-Free Nucleic Acid Logic Circuits , 2022 .