DNA multi-bit non-volatile memory and bit-shifting operations using addressable electrode arrays and electric field-induced hybridization

DNA has been employed to either store digital information or to perform parallel molecular computing. Relatively unexplored is the ability to combine DNA-based memory and logical operations in a single platform. Here, we show a DNA tri-level cell non-volatile memory system capable of parallel random-access writing of memory and bit shifting operations. A microchip with an array of individually addressable electrodes was employed to enable random access of the memory cells using electric fields. Three segments on a DNA template molecule were used to encode three data bits. Rapid writing of data bits was enabled by electric field-induced hybridization of fluorescently labeled complementary probes and the data bits were read by fluorescence imaging. We demonstrated the rapid parallel writing and reading of 8 (23) combinations of 3-bit memory data and bit shifting operations by electric field-induced strand displacement. Our system may find potential applications in DNA-based memory and computations.DNA based technology holds promise for non-volatile memory and computational tasks, yet the relatively slow hybridization kinetics remain a bottleneck. Here, Song et al. have developed an electric field-induced hybridization platform that can speed up multi-bit memory and logic operations.

[1]  Hieu Bui,et al.  Analog Computation by DNA Strand Displacement Circuits. , 2016, ACS synthetic biology.

[2]  G. Church,et al.  Large-scale de novo DNA synthesis: technologies and applications , 2014, Nature Methods.

[3]  Wei Wang,et al.  Electrochemically Generated Acid and Its Containment to 100 Micron Reaction Areas for the Production of DNA Microarrays , 2006, PloS one.

[4]  Lloyd M. Smith,et al.  A DNA computing readout operation based on structure-specific cleavage , 2001, Nature Biotechnology.

[5]  Nancy F. Hansen,et al.  Accurate Whole Human Genome Sequencing using Reversible Terminator Chemistry , 2008, Nature.

[6]  K. Shull,et al.  Anodic Electrodeposition of a Cationic Polyelectrolyte in the Presence of Multivalent Anions. , 2016, Langmuir : the ACS journal of surfaces and colloids.

[7]  Jian Ma,et al.  A Rewritable, Random-Access DNA-Based Storage System , 2015, Scientific Reports.

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

[9]  M. J. Heller,et al.  An active microelectronics device for multiplex DNA analysis , 1996 .

[10]  Jehoshua Bruck,et al.  Neural network computation with DNA strand displacement cascades , 2011, Nature.

[11]  G. Church,et al.  CRISPR-Cas encoding of a digital movie into the genomes of a population of living bacteria , 2017, Nature.

[12]  M. Heller,et al.  Electric field directed nucleic acid hybridization on microchips. , 1997, Nucleic acids research.

[13]  M. Heller DNA microarray technology: devices, systems, and applications. , 2002, Annual review of biomedical engineering.

[14]  David I. Lewin,et al.  DNA computing , 2002, Comput. Sci. Eng..

[15]  R J Lipton,et al.  DNA solution of hard computational problems. , 1995, Science.

[16]  Mette D. E. Jepsen,et al.  Construction of a fuzzy and Boolean logic gates based on DNA. , 2015, Small.

[17]  A. Condon,et al.  Surface-based DNA computing operations: DESTROY and READOUT. , 1999, Bio Systems.

[18]  Georg Seelig,et al.  A spatially localized architecture for fast and modular DNA computing. , 2017, Nature nanotechnology.

[19]  M. Heller,et al.  Rapid determination of single base mismatch mutations in DNA hybrids by direct electric field control. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[20]  Lloyd M. Smith,et al.  DNA computing on surfaces , 2000, Nature.

[21]  Kia Peyvan,et al.  CombiMatrix oligonucleotide arrays: genotyping and gene expression assays employing electrochemical detection. , 2007, Biosensors & bioelectronics.

[22]  Tomasz Popławski,et al.  [DNA computing]. , 2011, Postepy biochemii.

[23]  Olgica Milenkovic,et al.  Portable and Error-Free DNA-Based Data Storage , 2016, Scientific Reports.

[24]  Sadik C Esener,et al.  Interaction of Nanoparticles at the DEP Microelectrode Interface under High Conductance Conditions. , 2009, Electrochemistry communications.

[25]  M. Heller,et al.  A Programmable DNA Double-Write Material: Synergy of Photolithography and Self-Assembly Nanofabrication. , 2017, ACS applied materials & interfaces.

[26]  Andy Extance,et al.  How DNA could store all the world’s data , 2016, Nature.

[27]  Reza M Zadegan,et al.  Nucleic acid memory. , 2016, Nature materials.

[28]  M. Heller,et al.  Microelectronic array devices and techniques for electric field enhanced DNA hybridization in low‐conductance buffers , 2002, Electrophoresis.

[29]  Edwin M. Southern,et al.  Electrochemically directed synthesis of oligonucleotides for DNA microarray fabrication , 2005, Nucleic acids research.

[30]  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 .

[31]  M. Heller,et al.  Preparation and hybridization analysis of DNA/RNA from E. coli on microfabricated bioelectronic chips , 1998, Nature Biotechnology.

[32]  Lloyd M Smith,et al.  Demonstration of a universal surface DNA computer. , 2004, Nucleic acids research.

[33]  Li Yang,et al.  A fully multiplexed CMOS biochip for DNA analysis , 2000 .

[34]  J. S. Lee,et al.  Comparison of the Nernst-Planck model and the Poisson-Boltzmann model for electroosmotic flows in microchannels. , 2007, Journal of colloid and interface science.

[35]  Henrik Ekström,et al.  COMSOL Multiphysics®: Finite element software for electrochemical analysis. A mini-review , 2014 .

[36]  Luca Cardelli,et al.  Programmable chemical controllers made from DNA. , 2013, Nature nanotechnology.

[37]  G. Church,et al.  Next-Generation Digital Information Storage in DNA , 2012, Science.

[38]  G. J. Shaw,et al.  Comparison of electrical conductivities of various brain phantom gels: Developing a 'Brain Gel Model' , 2012, Materials science & engineering. C, Materials for biological applications.

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

[40]  John H. Reif Scaling Up DNA Computation , 2011, Science.

[41]  Robert N Grass,et al.  Robust chemical preservation of digital information on DNA in silica with error-correcting codes. , 2015, Angewandte Chemie.

[42]  Michael J Heller,et al.  Device for dielectrophoretic separation and collection of nanoparticles and DNA under high conductance conditions , 2015, Electrophoresis.

[43]  Sudheer Sahu,et al.  Design of an Autonomous DNA Nanomechanical Device Capable of Universal Computation and Universal Translational Motion , 2004, DNA.

[44]  Ewan Birney,et al.  Towards practical, high-capacity, low-maintenance information storage in synthesized DNA , 2013, Nature.

[45]  Andrew Currin,et al.  Computing exponentially faster: implementing a non-deterministic universal Turing machine using DNA , 2016, Journal of The Royal Society Interface.

[46]  Chang-Biau Yang,et al.  A DNA solution of SAT problem by a modified sticker model. , 2005, Bio Systems.

[47]  M. Heller,et al.  Active microelectronic chip devices which utilize controlled electrophoretic fields for multiplex DNA hybridization and other genomic applications , 2000, Electrophoresis.