Conformation-dependent rewritable biomolecular memory device

Abstract

A memory system, including: a nucleic acid memory device including a nucleic acid molecule comprising a first end and a second end, and further including two or more conformations; a first electrically conductive contact coupled to the first end of the nucleic acid molecule; and a second electrically conductive contact coupled to the second end of the nucleic acid molecule. A controller is included to perform operations including: measuring a first conductance state of the nucleic acid molecule in a first conformation of the two or more conformations, or measuring a second conductance state of the nucleic acid molecule in a second conformation of the two or more conformations. The first conductance state is associated with a first logic state and the second conductance state is associated with a second logic state. Also disclosed is a memory array including two or more memory systems.

Description

CONFORMATION-DEPENDENT REWRITABLE BIOMOLECULAR MEMORY DEVICECROSS-REFERENCE(S) TO RELATED APPLICATION(S)

[0001] This application claims the benefit of U. S. Patent Application No.63 / 717,907, filed November 8, 2024, the disclosure of each is expressly incorporated herein by reference in its entirety.STATEMENT REGARDING SEQUENCE LISTING

[0002] The Sequence Listing XML associated with this application is provided in XML format and is hereby incorporated by reference into the specification. The name of the XML file containing the sequence listing is 3915-P1376WO. UW_Sequence_Listing.xml. The XML file is 16,649 bytes; was created on October 17, 2025; and is being submitted electronically via Patent Center with the filing of the specification.STATEMENT OF GOVERNMENT LICENSE RIGHTS

[0003] This invention was made with government support under Grant No.2328217, awarded by the National Science Foundation. The government has certain rights in the invention.BACKGROUND

[0004] The folding and unfolding of RNA transform a simple nucleotide chain into versatile 3D molecular complexes, playing a pivotal role in numerous biological functions. For instance, RNA catalyzes peptide bond formation, regulates translation, assists in replication, and supports both protein synthesis and viral propagation. This intricate involvement of RNA complexes in modulating critical biological processes has motivated researchers to investigate its structural attributes for decades. RNA folding has been proposed as a two-level problem: secondary and tertiary.

[0005] A significant effort has been made to predict and determine these secondary and tertiary structures based on RNA sequences. Secondary structures are largely governed by Watson-Crick (WC) and wobble base pairing while transition to tertiary structures is more complicated. Although these computational studies shed light on the folding patterns of RNA, they do not provide any insight into the underlying charge transport properties, which is crucial for the design of next-generation nanotechnology.

[0006] RNA origami enables the design of multitudes of complex RNA architectures for applications in medicines and synthetic biology. For instance, the selffolding of single-stranded RNA (ssRNA) can lead to building complex nanostructures without knots.

[0007] Unlike DNA, RNA charge transport has not been extensively explored. Single-molecule conductance measurements have revealed that RNAs exhibit comparable, if not higher, conductance than DNAs. The conductance of single- and double-stranded RNAs have been reported to be around 0.001 Go, where Go is the quantum conductance. While ssRNA may be conformationally programmed through selection of nucleotide sequences, the underlying charge transport (CT) properties of RNA are not well known. Moreover, because of the growing need for advances in electronic devices with tunable properties, in particular memory devices, it is desirable to identify alternative materials for manufacturing memory devices.

[0008] Accordingly, there is a long-felt need in the art for systems and methods for storing memory on nucleic acid devices.SUMMARY

[0009] To address these and related challenges the present disclosure provides memory systems, memory arrays, and methods of storing and retrieving data from a memory system and / or array.

[0010] This summary is provided to introduce a selection of concepts in a simplified form that are further described below in the Detailed Description. This summary is not intended to identify key features of the claimed subject matter, nor is it intended to be used as an aid in determining the scope of the claimed subject matter.

[0011] In an aspect, the present disclosure provides a memory system, comprising: a nucleic acid memory device comprising: a nucleic acid molecule comprising a first end and a second end, and further comprising two or more conformations; a first electrically conductive contact coupled to the first end of the nucleic acid molecule; and a second electrically conductive contact coupled to the second end of the nucleic acid molecule; and a controller operatively coupled to the nucleic acid memory device, the controller including at least one processor and a computer-readable medium having computer-executable instructions stored thereon that, in response to execution by the at least one processor, cause the controller to perform operations including: (i) measuring a first conductance state of the nucleic acid molecule in a first conformation of the two ormore conformations, or (ii) measuring a second conductance state of the nucleic acid molecule in a second conformation of the two or more conformations, wherein the first conductance state is associated with a first logic state and the second conductance state is associated with a second logic state.

[0012] In an embodiment, the memory system further comprises a stressing device configured to manipulate a conformation of the nucleic acid molecule; and a controller operatively coupled to the stressing device, the controller including at least one processor and a computer-readable medium having computer-executable instructions stored thereon that, in response to execution by the at least one processor, cause the controller to perform operations including: manipulating, with the stressing device, the conformation of the nucleic acid molecule from the first conformation to the second conformation, or from the second conformation to the first conformation.

[0013] In an embodiment, the nucleic acid molecule is a single-stranded nucleic acid molecule. In an embodiment, the nucleic acid molecule is a double-stranded nucleic acid molecule. In an embodiment, the nucleic acid molecule is an RNA molecule. In an embodiment, the nucleic acid molecule is a DNA molecule. In an embodiment, the nucleic acid molecule comprises between 2 and about 100 base pairs. In an embodiment, the nucleic acid molecule comprises between about 5 and about 50 base pairs. In an embodiment, the nucleic acid molecule comprises between about 10 and about 25 base pairs. In an embodiment, the nucleic acid molecule comprises about 10 base pairs.

[0014] In an embodiment, the stressing device is configured to adjust a pH of a solution comprising the nucleic acid molecule. In an embodiment, the stressing device is configured to adjust a salt concentration of a solution comprising the nucleic acid molecule. In an embodiment, the stressing device is a mechanical strain-inducing device configured to manipulate the conformation of the nucleic acid molecule. In an embodiment, the mechanical strain-inducing device is selected from the group consisting of optical tweezers, magnetic tweezers, a piezoelectric device coupled to the first or second electrically conductive contact, and a combination thereof. In an embodiment, the stressing device is an electric field generating device configured to apply an electric field to the first or second electrically conductive contact, thereby inducing a change in conformation in the nucleic acid molecule.

[0015] In an embodiment, the first electrically conductive contact and second electrically conductive contact each comprise quasi-one-dimensional semiconductingwires. In an embodiment, the first electrically conductive contact is selected from the group consisting of a carbon nanotube, a doped boron nitride nanotube, a graphene nanoribbon, a metal nanowire, a doped semiconducting nanowire, and a metallo-intercalated DNA strand. In an embodiment, the second electrically conductive contact is selected from the group consisting of a carbon nanotube, a doped boron nitride nanotube, a graphene nanoribbon, a metal nanowire, a doped semiconducting nanowire, and a metallo-intercalated DNA strand.

[0016] In an embodiment, the first conductance is different from the second conductance. In an embodiment, a conductance of the nucleic acid in a substantially folded conformation is larger in magnitude than a conductance of the nucleic acid when it is in a substantially unfolded conformation. In an embodiment, a conductance of the nucleic acid in a substantially folded conformation is smaller in magnitude than a conductance of the nucleic acid when it is in a substantially unfolded conformation.

[0017] In an embodiment, the first conductance state of the nucleic acid and the second conductance state of the nucleic acid strand are different by a factor of between about 10 to about 10000. In an embodiment, the first conductance state of the nucleic acid and the second conductance state of the nucleic acid strand are different by a factor of between about 100 to about 1000.

[0018] In an embodiment, the nucleic acid memory device is a first nucleic acid memory device, the memory system further comprising a second nucleic acid memory device comprising: a second nucleic acid molecule comprising a first end and a second end, and further comprising two or more conformations; a first electrically conductive contact coupled to a first end of the second nucleic acid molecule; and a second electrically conductive contact coupled to a second end of the second nucleic acid molecule.

[0019] In an embodiment, the logic state is a first logic state, and wherein the computer-executable instructions stored thereon the controller, in response to execution by the at least one processor, cause the controller to perform operations including: measuring a second logic state of the second nucleic acid molecule by either (i) measuring a first conductance of the second nucleic acid molecule in a first conformation of the two or more conformations, or (ii) measuring a second conductance of the second nucleic acid molecule in a second conformation of the two or more conformations.

[0020] In an aspect, the present disclosure provides a nucleic acid memory array, comprising: a first nucleic acid memory device comprising: a first nucleic acid moleculecomprising a first end and a second end, and further comprising two or more conformations; a first electrically conductive contact coupled to a first end of the first nucleic acid molecule; and a second electrically conductive contact coupled to a second end of the first nucleic acid molecule; a second nucleic acid memory device comprising: a second nucleic acid molecule comprising a first end and a second end, and further comprising two or more conformations; a first electrically conductive contact coupled to a first end of the second nucleic acid molecule; and a second electrically conductive contact coupled to a second end of the second nucleic acid molecule; and a controller operatively coupled to the first nucleic acid memory device and to the second nucleic acid memory device, the controller including at least one processor and a computer-readable medium having computer-executable instructions stored thereon that, in response to execution by the at least one processor, cause the controller to perform operations including: measuring a first logic state of the first nucleic acid molecule by either (i) measuring a first conductance of the first nucleic acid molecule in a first conformation of the two or more conformations, or (ii) measuring a second conductance of the first nucleic acid molecule in a second conformation of the two or more conformations; and measuring a second logic state of the second nucleic acid molecule by either (i) measuring a first conductance of the second nucleic acid molecule in a first conformation of the two or more conformations, or (ii) measuring a second conductance of the second nucleic acid molecule in a second conformation of the two or more conformations.

[0021] In an embodiment, the nucleic acid memory array further comprises: a stressing device configured to independently manipulate a conformation of the first nucleic acid molecule and the second nucleic acid molecule; and a controller operatively coupled to the stressing device, the controller including at least one processor and a computer-readable medium having computer-executable instructions stored thereon that, in response to execution by the at least one processor, cause the controller to perform operations including: manipulating, with the stressing device, the conformation of the first nucleic acid molecule from the first conformation to the second conformation, or from the second conformation to the first conformation; and manipulating, with the stressing device, the conformation of the second nucleic acid molecule from the first conformation to the second conformation, or from the second conformation to the first conformation.

[0022] In an aspect, the present disclosure provides a method comprising: storing logic data in a nucleic acid memory system by modulating a conformation of a nucleic acidmolecule therein between (i) a first conformation and a second conformation, or (ii) the second conformation and the first conformation, the nucleic acid memory system comprising: the nucleic acid molecule, comprising a first end and a second end; a first electrically conductive contact coupled to a first end of the nucleic acid molecule; and a second electrically conductive contact coupled to a second end of the nucleic acid molecule; and retrieving the logic data from the nucleic acid memory system by measuring, with a conductance measurement device coupled to the first and second ends of the nucleic acid molecule, a conductance value across the nucleic acid molecule.

[0023] In an aspect, the present disclosure provides a non-transitory machine-readable storage medium having instructions stored thereon, which when executed by a processing system, cause the processing system to perform a method comprising: storing logic data in a nucleic acid memory system by modulating a conformation of a nucleic acid molecule therein between (i) a first conformation and a second conformation, or (ii) the second conformation and the first conformation, the nucleic acid memory system comprising: the nucleic acid molecule, comprising a first end and a second end; a first electrically conductive contact coupled to a first end of the nucleic acid molecule; and a second electrically conductive contact coupled to a second end of the nucleic acid molecule; and retrieving the logic data from the nucleic acid memory system by measuring, with a conductance measurement device coupled to the first and second ends of the nucleic acid molecule, a conductance value across the nucleic acid molecule.DESCRIPTION OF THE DRAWINGS

[0024] The foregoing aspects and many of the attendant advantages of this the subject matter of the present disclosure will become more readily appreciated as the same become better understood by reference to the following detailed description, when taken in conjunction with the accompanying drawings.

[0025] FIGURE 1A: Molecular Dynamics (MD) results: single-stranded RNA (ssRNA) vs double-stranded RNA (dsRNA). ID root mean square deviation (RMSD) vs. time; dotted black lines indicate the mean RMSDs. RMSD values help to understand how the conformations differ during the MD simulations.

[0026] FIGURE IB: Molecular Dynamics results: ssRNA vs dsRNA. 2D RMSD vs. time.

[0027] FIGURE 1C: Molecular Dynamics results: ssRNA vs dsRNA. End-to-end phosphorus distances vs. time. The dotted lines are drawn to show that ssRNA mostlyfluctuates between folded and unfolded configurations, while dsRNA is comparatively stable.

[0028] FIGURE ID: Molecular Dynamics results: ssRNA vs dsRNA. Coefficient of variation (σ / μ) for the seven backbone dihedral angles.

[0029] FIGURE IE: Molecular Dynamics results: ssRNA vs dsRNA. Hydrogen bond heatmaps between bases of ssRNA / base-pairs of dsRNA. The color bars (in units of A) represent average hydrogen bonds over 100,000 conformations. An enlarged version of the heatmaps with corresponding average H-bond numbers are provided in FIGURE 11 A and FIGURE 1 IB for ssRNA and dsRNA, respectively.

[0030] FIGURE 2A: Conductance stochasticity of ssRNA. Representative backbone orientations of ssRNA for nominal Pats values 10, 15, 20, 25 & 30 A.

[0031] FIGURE 2B: Conductance stochasticity of ssRNA. Left: Conductance as a function of time. The markers are coordinated to the ^Pcusvalues depicted in FIGURE 2A. Right: Probability distribution of all the log of conductance values obtained from 123 conformations (bar plots). The dotted line is the fitted curve with gamma distribution (a = 5.3424, p = 0.8767). The shaded regions enclosed within dotted envelopes represent the conductance dispersion limits of dsRNA of this work. The conductance values for dsRNA have been provided in Table 1.

[0032] FIGURE 3 A: Wavefunction distribution. Configuration of the lowest and highest conductance configurations (LCC and HCC respectively) for end-to-end phosphorus distances Pais'. 15 A, with orbital maps of corresponding HOMO (LCC: top; HCC: right) and HOMO-1 (LCC: bottom; HCC: left) energy level for nucleic acid with SEQ ID NO: 1. Wavefunctions with absolute value greater than or equal to 0.005 are shown.

[0033] FIGURE 3B: Wavefunction distribution. Configuration of the lowest and highest conductance configurations (LCC and HCC respectively) for end-to-end phosphorus distances ^PdiS20 A, with orbital maps of corresponding HOMO (LCC: bottom; HCC: top) and HOMO-1 (LCC: top; HCC: bottom) energy level for nucleic acid with SEQ ID NO: 1. Wavefunctions with absolute value greater than or equal to 0.005 are shown.

[0034] FIGURE 3C: Wavefunction distribution. Configuration of the lowest and highest conductance configurations (LCC and HCC respectively) for end-to-end phosphorus distances Pats'. 25 A, with orbital maps of corresponding HOMO (LCC: top;HCC; bottom) and HOMO-1 (LCC: bottom; HCC: top) energy level for nucleic acid with SEQ ID NO: 1. Wavefunctions with absolute value greater than or equal to 0.005 are shown.

[0035] FIGURE 4A: Charge transport properties. Density of states and transmission profiles for HCCs and LCCs are shown for ^PdiS15 A. (Top row) Partial density of states (PDOS) for every residue site. The left and right panels show the PDOS distributions for LCC and HCC conformations, respectively. (Bottom row) Transmission profiles as a function of energy. The ratios of transmission at HOMO energy level for HCC to LCC are also indicated.

[0036] FIGURE 4B: Charge transport properties. Density of states and transmission profiles for HCCs and LCCs are shown for APdis20 A. (Top row) Partial density of states (PDOS) for every residue site. The left and right panels show the PDOS distributions for LCC and HCC conformations, respectively. (Bottom row) Transmission profiles as a function of energy. The ratios of transmission at HOMO energy level for HCC to LCC are also indicated.

[0037] FIGURE 4C: Charge transport properties. Density of states and transmission profiles for HCCs and LCCs are shown for APdis25 A. (Top row) Partial density of states (PDOS) for every residue site. The left and right panels show the PDOS distributions for LCC and HCC conformations, respectively. (Bottom row) Transmission profiles as a function of energy. The ratios of transmission at HOMO energy level for HCC to LCC are also indicated.

[0038] FIGURE 5A: Impact of salt concentration, according to embodiments of the present disclosure. 1D-RMSD results for (top panel) negligible, N (middle panel) low, L and (bottom panel) high, H salt concentrations. The dotted lines represent the average RMSD.

[0039] FIGURE 5B: Impact of salt concentration, according to embodiments of the present disclosure. 2D RMSD heatmaps showing higher salt concentration leads to overall lower RMSD.

[0040] FIGURE 5C: Impact of salt concentration, according to embodiments of the present disclosure. End-to-end phosphorus distances. The dotted lines represent the average APdis.

[0041] FIGURE 5D: Impact of salt concentration, according to embodiments of the present disclosure. Coefficient of variation (σ / μ) for negligible (top bars), low (middle bars), and high (bottom bars) salt concentrations.

[0042] FIGURE 5E: Impact of salt concentration, according to embodiments of the present disclosure. Hydrogen bond heatmaps for (top panel) low and (bottom panel) high salt concentrations. Shading bars represent average hydrogen bonds over 100,000 conformations. Fewer number of hydrogen bonds between non-adjacent bases suggest a reduced folding tendency. The numbers on each grid have been rounded off to one place after decimal and nearest integer.

[0043] FIGURE 6A: A memory system according to embodiments of the present disclosure.

[0044] FIGURE 6B: A memory array according to embodiments of the present disclosure.

[0045] FIGURE 7: A method according to embodiments of the present disclosure.

[0046] FIGURE 8: Pdiscategory -wise conductance spectrum (see the grey circles). The 10thand 90thpercentiles (represented by lower and upper dotted envelopes respectively) of conductance values for each Pdiscategory are also shown. The average conductance decreases from folded (ΔPdis= 10, 15 A) to unfolded (ΔPdis= 25, 30 Å) states. Additionally, the conductance spread increases for larger ΔPdisvalues.

[0047] FIGURE 9A: Probability of finding an electron at HOMO energy level for LCCs and HCCs for all PdiS= 10A category.

[0048] FIGURE 9B: Probability of finding an electron at HOMO energy level for LCCs and HCCs for allcategory.

[0049] FIGURE 9C: Probability of finding an electron at HOMO energy level for LCCs and HCCs for all PdiS= 20A category.

[0050] FIGURE 9D: Probability of finding an electron at HOMO energy level for LCCs and HCCs for all PdiS= 25A category.

[0051] FIGURE 9E: Probability of finding an electron at HOMO energy level for LCCs and HCCs for all PdiS= 30A category.

[0052] FIGURE 10: A possible experimental setup to modulate degree of ssRNA folding, thereby its conductance, is shown, according to embodiments of the present disclosure. A complete switching cycle in which the left contact will be fixed while theright contact will be modulated to increase (configs: A to E) and decrease (configs: E to I) ssRNA folding state. The switching timescale will depend on the rate of right contact modulation. The separation between the two contacts in all configurations is denoted by Pdis. In all the sub-figures, ssRNA is illustrated by the curved line.

[0053] FIGURE 11: Potential electrode configurations which will be used to realize ssRNA-based memory devices, according to embodiments of the present disclosure. (Top panel) The first contact setup has ssRNA device positioned between two gold electrodes. (Middle panel) The second contact setup has ssRNA device trapped between two CNT electrodes. (Bottom panel) ssRNA is captured between two piezo contact and is placed on a bent substrate. In all these configurations, a third terminal may be added to the substrate to add another control knob in the experiments.

[0054] FIGURE 12 A: Most probable structures obtained after clustering of each sequence are shown for adenine (i, ii, Hi, iv) base substitution, according to embodiments of the present disclosure. Various categories of barriers are plotted, namely, single (i), double (ii), alternate double (Hi), and off-center double (iv). Corresponding sequences are mentioned at the top of each column.

[0055] FIGURE 12B: Most probable structures obtained after clustering of each sequence are shown for cytosine (i, ii, Hi, iv) base substitution, according to embodiments of the present disclosure. Various categories of barriers are plotted, namely, single (i), double (ii), alternate double (Hi), and off-center double (iv). Corresponding sequences are mentioned at the top of each column.

[0056] FIGURE 12C: Most probable structures obtained after clustering of each sequence are shown for uracil (i, ii, Hi, iv) base substitution, according to embodiments of the present disclosure. Various categories of barriers are plotted, namely, single (i), double (ii), alternate double (Hi), and off-center double (iv). Corresponding sequences are mentioned at the top of each column.DETAILED DESCRIPTION

[0057] The conformation of single stranded RNA (ssRNA), DNA, and their double stranded counterparts including DNA-RNA hybrids and DNA origami-based nanostructures can be changed repeatedly. These nanostructures are extremely stable to repeated conformational change. This forms the basis for a rewritable nanoscale memory technology based on these nanostructures. The different conformations have unique resistance levels which codes for the different logic levels. This disclosure reveals a largechange in conductance and the stability of the conformations over a time scale useful to memory technologies.

[0058] In an embodiment, the stability of the conformation’s time-scale exceed the 100 ns to 10 micro-seconds timescale. In an embodiment, the change in resistance as a result of conformation change can be anywhere from two-times to many thousand-times, depending on the sequence. While these are provided as examples, stability for longer time scales is within the scope of this disclosure. In an embodiment, the conformation change of the nanostructure can be effectively induced by a number of external stimuli which includes mechanical strain, electromechanical strain, pH change, change in salt conformation, change in gate voltage and so on. In an embodiment, the electrical leads to the biomolecules could be conventional contacts or nanoscale contacts such as carbon nanotubes, nanowires and metal-intercalated nanowires.

[0059] In some aspects, the present disclosure provides a memory system, comprising: a nucleic acid memory device comprising: a nucleic acid molecule comprising a first end and a second end, and further comprising two or more conformations; a first electrically conductive contact coupled to the first end of the nucleic acid molecule; and a second electrically conductive contact coupled to the second end of the nucleic acid molecule; and a controller operatively coupled to the nucleic acid memory device, the controller including at least one processor and a computer-readable medium having computer-executable instructions stored thereon that, in response to execution by the at least one processor, cause the controller to perform operations including: (i) measuring a first conductance state of the nucleic acid molecule in a first conformation of the two or more conformations, or (ii) measuring a second conductance state of the nucleic acid molecule in a second conformation of the two or more conformations, wherein the first conductance state is associated with a first logic state and the second conductance state is associated with a second logic state.

[0060] In this regard, FIGURE 6A is a schematic illustration of a nucleic acid memory device according to an aspect of the present disclosure. FIGURE 6A includes nucleic acid memory device 100 which is in a first conformation. Nucleic acid memory device 100 includes a first electrically conductive contact 102, a second electrically conductive contact 104, and a nucleic acid molecule 106. A first end of the nucleic acid molecule 106 is coupled to the first electrically conductive contact 102. A second end of the nucleic acid molecule 106 is coupled to the second electrically conductive contact 104.While a single stranded nucleic acid molecule, such as ssRNA, is depicted in FIGURE 6A for clarity, it should be understood that nucleic acid memory device 100 may include other nucleic acid molecules, including single stranded DNA (ssDNA), double stranded DNA (dsDNA), or double stranded RNA (dsRNA). Additionally, other quantities of nucleic acids may be used, including triple stranded nucleic acids. It should be understood that these embodiments fall within the scope of the present disclosure.

[0061] FIGURE 6A also includes nucleic acid memory device 100’, which represents nucleic acid memory device 100 in a second conformation. Nucleic acid memory device 100’ includes a first electrically conductive contact 102’, a second electrically conductive contact 104’, and a nucleic acid molecule 106’. A first end of the nucleic acid molecule 106’ is coupled to the first electrically conductive contact 102’. A second end of the nucleic acid molecule 106’ is coupled to the second electrically conductive contact 104’. Nucleic acid memory device 100’ may be an example of nucleic acid memory device 100 after nucleic acid molecule 106 undergoes a conformational change from the first conformation to the second conformation.

[0062] In this regard, arrow 110 represents a transformation of the device 100 / 100’ from the first configuration to the second configuration via the application of mechanical strain. Similarly, arrow 120 represents a transformation of the first configuration to the second configuration via application of electromechanical strain. While mechanical strain and electromechanical strain are depicted in the schematic of FIGURE 6A, it should be noted that a conformation change from the first to second conformations may also occur because of a pH change, an application of a gate voltage, or a change in salt concentration. Furthermore, while FIGURE 6A depicts a transformation from a first configuration to a second configuration, it should be understood that a transformation may also occur from the second configuration to the first configuration. In some embodiments, this transformation may be reversible and repeatable.

[0063] It should also be understood that memory device 100 may be part of a memory system or memory array, such as the memory array 200 depicted in FIGURE 6B and described further below.

[0064] In some embodiments, the memory system further comprises a stressing device configured to manipulate a conformation of the nucleic acid molecule; and a controller operatively coupled to the stressing device, the controller including at least one processor and a computer-readable medium having computer-executable instructionsstored thereon that, in response to execution by the at least one processor, cause the controller to perform operations including: manipulating, with the stressing device, the conformation of the nucleic acid molecule from the first conformation to the second conformation, or from the second conformation to the first conformation. In this regard, in the schematic illustration of FIGURE 6 A, arrows 110 and 120 represent the actions of a stressing device interfacing with a memory device of a memory system.

[0065] In some embodiments, the nucleic acid molecule is a single-stranded nucleic acid molecule.

[0066] In some embodiments, the nucleic acid molecule is a double-stranded nucleic acid molecule.

[0067] In some embodiments, the nucleic acid molecule is an RNA molecule.

[0068] In some embodiments, the nucleic acid molecule is a DNA molecule.

[0069] In some embodiments, the nucleic acid molecule comprises between 2 and about 100 base pairs.

[0070] In some embodiments, the nucleic acid molecule comprises between about 5 and about 50 base pairs.

[0071] In some embodiments, the nucleic acid molecule comprises between about 10 and about 25 base pairs.

[0072] In some embodiments, the nucleic acid molecule comprises about 10 base pairs.

[0073] In some embodiments, the nucleic acid molecule is any of the nucleic acid molecules described in SEQ ID NO: 1 - SEQ ID NO: 14, as discussed further below with respect to Table 3.

[0074] In some embodiments, the nucleic acid molecule is a nucleic acid molecule at least 75% identical to a nucleic acid molecule according to any of SEQ ID NOS: 1-14.

[0075] In some embodiments, the nucleic acid molecule is a nucleic acid molecule at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or greater identical to a nucleic acid molecule according to any of SEQ ID NOS: 1-14.

[0076] As used herein, “at least X% identical” or “having at least X% sequence identity” means that the nucleic acid molecule differs in its full-length nucleic acid sequence by (100-X)% or less (including any nucleic acid residue substitutions, deletions,additions, or insertions) relative to a reference sequence, where X may be 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or greater.

[0077] In some embodiments, the stressing device is configured to adjust a pH of a solution comprising the nucleic acid molecule. In some embodiments, the stressing device is configured to adjust a salt concentration of a solution comprising the nucleic acid molecule. Without wishing to be bound by any particular theory, when the memory system is in contact with a solution comprising dissolved salts, a change in salt concentration may change the conformation of the nucleic acid. For instance, changes in the salt concentration may increase intramolecular forces between segments of the nucleic acid. This may be used to alter the rate of fluctuation between compressed and expanded conformations by maintaining the nucleic acid in its initial configuration for a longer period of time. In this manner, it is possible to tune logic states by altering the conductance. In some instances, increased intramolecular forces between segments of the nucleic acid place the nucleic acid in a relatively compressed or extended conformation. In other instances, changes in the salt concentration may decrease the intramolecular forces between segments of the nucleic acid, thereby placing the nucleic acid in a relatively expanded conformation.

[0078] In some embodiments, the stressing device is a mechanical straininducing device configured to manipulate the conformation of the nucleic acid molecule. In some embodiments, the mechanical strain-inducing device is selected from the group consisting of optical tweezers, magnetic tweezers, a piezoelectric device coupled to the first or second electrically conductive contact, and a combination thereof. Without wishing to be bound by any particular theory, advantages of a mechanical strain-inducing device may include interfacing with other electrical components when embedded in a chip, and rapid and selective control of the memory states of the memory system.

[0079] In some embodiments, the stressing device is an electric field generating device configured to apply an electric field to the first or second electrically conductive contact, thereby inducing a change in conformation in the nucleic acid molecule. In some embodiments, the FIGURE 11 and FIGURE 12 are examples depicting stressing devices according to the present disclosure.

[0080] As used herein, an “electrically conductive contact” is a component that is sized and shaped to be suitable for the transfer of electrical current between two points in a circuit. In this regard, in some embodiments, the first electrically conductive contactand second electrically conductive contact each comprise quasi-one-dimensional semiconducting wires.

[0081] In some embodiments, the first electrically conductive contact is selected from the group consisting of a carbon nanotube, a doped boron nitride nanotube, a graphene nanoribbon, a metal nanowire, a doped semiconducting nanowire, and a metallo-intercalated DNA strand. In some embodiments, the first electrically conductive contact is a carbon nanotube. In some embodiments, the first electrically conductive contact is a doped boron nitride nanotube. In some embodiments, the first electrically conductive contact is a graphene nanoribbon. In some embodiments, the first electrically conductive contact is a metal nanowire. In some embodiments, the first electrically conductive contact is a doped semiconducting nanowire. In some embodiments, the first electrically conductive contact is a metal intercalated DNA strand.

[0082] In some embodiments, the second electrically conductive contact is selected from the group consisting of a carbon nanotube, a doped boron nitride nanotube, a graphene nanoribbon, a metal nanowire, a doped semiconducting nanowire, and a metallo-intercalated DNA strand. In some embodiments, the second electrically conductive contact is a carbon nanotube. In some embodiments, the second electrically conductive contact is a doped boron nitride nanotube. In some embodiments, the second electrically conductive contact is a graphene nanoribbon. In some embodiments, the second electrically conductive contact is a metal nanowire. In some embodiments, the second electrically conductive contact is a doped semiconducting nanowire. In some embodiments, the second electrically conductive contact is a metallo-intercalated DNA strand.

[0083] The coupling of a nucleic acid to an electrically conductive contact may be performed by any method known to those of ordinary skill in the art.

[0084] In some embodiments, the first conductance is different from the second conductance. In some embodiments, a conductance of the nucleic acid in a substantially folded conformation is larger in magnitude than a conductance of the nucleic acid when it is in a substantially unfolded conformation. In some embodiments, a conductance of the nucleic acid in a substantially folded conformation is smaller in magnitude than a conductance of the nucleic acid when it is in a substantially unfolded conformation. For instance, the conformation-dependency of conductance of a nucleic acid molecule is discussed further below with respect to FIGURE 8.

[0085] In some embodiments, the first conductance state of the nucleic acid and the second conductance state of the nucleic acid strand are different by a factor of between about 10 to about 10000. In some embodiments, the first conductance state of the nucleic acid and the second conductance state of the nucleic acid strand are different by a factor of between about 100 to about 1000. Without wishing to be bound by any particular theory, the difference in conductance states between two conformations may be tuned or adjusted so as to make a memory system according to the present disclosure more robust against overwriting, or more flexible for rewritable memory. A higher difference between conductance values improves the differentiation between two logic levels. A lower conductance ratio may provide notable advantages to the production of memory devices.

[0086] In some embodiments, the nucleic acid memory device is a first nucleic acid memory device, the memory system further comprising a second nucleic acid memory device comprising: a second nucleic acid molecule comprising a first end and a second end, and further comprising two or more conformations; a first electrically conductive contact coupled to a first end of the second nucleic acid molecule; and a second electrically conductive contact coupled to a second end of the second nucleic acid molecule. In some embodiments, the memory system further comprises a third nucleic acid memory device, a fourth nucleic acid memory device, a fifth nucleic acid memory device, or six or more nucleic acid memory devices.

[0087] In some embodiments, the logic state is a first logic state, and wherein the computer-executable instructions stored thereon the controller, in response to execution by the at least one processor, cause the controller to perform operations including: measuring a second logic state of the second nucleic acid molecule by either (i) measuring a first conductance of the second nucleic acid molecule in a first conformation of the two or more conformations, or (ii) measuring a second conductance of the second nucleic acid molecule in a second conformation of the two or more conformations.

[0088] In some aspects, the present disclosure provides a nucleic acid memory array, comprising: a first nucleic acid memory device comprising: a first nucleic acid molecule comprising a first end and a second end, and further comprising two or more conformations; a first electrically conductive contact coupled to a first end of the first nucleic acid molecule; and a second electrically conductive contact coupled to a second end of the first nucleic acid molecule; a second nucleic acid memory device comprising: a second nucleic acid molecule comprising a first end and a second end, and furthercomprising two or more conformations; a first electrically conductive contact coupled to a first end of the second nucleic acid molecule; and a second electrically conductive contact coupled to a second end of the second nucleic acid molecule; and a controller operatively coupled to the first nucleic acid memory device and to the second nucleic acid memory device, the controller including at least one processor and a computer-readable medium having computer-executable instructions stored thereon that, in response to execution by the at least one processor, cause the controller to perform operations including: measuring a first logic state of the first nucleic acid molecule by either (i) measuring a first conductance of the first nucleic acid molecule in a first conformation of the two or more conformations, or (ii) measuring a second conductance of the first nucleic acid molecule in a second conformation of the two or more conformations; and measuring a second logic state of the second nucleic acid molecule by either (i) measuring a first conductance of the second nucleic acid molecule in a first conformation of the two or more conformations, or (ii) measuring a second conductance of the second nucleic acid molecule in a second conformation of the two or more conformations.

[0089] The memory devices of the memory array are, in some embodiments, examples of memory device 100. Furthermore, while the memory array is described with respect to a first nucleic acid memory device and a second nucleic acid memory device, it should be understood that the memory array may include any number of nucleic acid memory devices, including between 2 and 10 nucleic acid memory devices, between 10 and 100 nucleic acid memory devices, between 100 and 1,000 nucleic acid memory devices, between 1,000 and 10,000 nucleic acid memory devices, between 10,000 and 1,000,000 nucleic acid memory devices, and any combination thereof.

[0090] FIGURE 6B provides a schematic illustration of memory array 200 including five memory devices. Memory array 200 is depicted to include a plurality of first electrically conductive contacts (such as electrically conductive contacts 202a, 202b, 202c, 202d, and 202e); a plurality of second electrically conductive contacts, (such as electrically conductive contacts 204a, 204b, 204c, 204d, and 204e); and a plurality of nucleic acid molecules (such as nucleic acid molecules 206a, 206b, 206c, 206d, and 206e). A first end of each nucleic acid molecule is coupled to an end of each first electrically conductive contact. A second end of each nucleic acid molecule is coupled to an end of each second electrically conductive contact. In this regard, memory array 200 includes a plurality of memory devices (such as those depicted in memory device 100). Moreover, while memoryarray 200 is depicted in FIGURE 6B where each memory device is in a first configuration, it should be understood that each memory device of the memory array 200 may independently be placed into a first or second configuration in any of the manners described in the present disclosure.

[0091] In some embodiments, the nucleic acid memory array further comprises: a stressing device configured to independently manipulate a conformation of the first nucleic acid molecule and the second nucleic acid molecule; and a controller operatively coupled to the stressing device, the controller including at least one processor and a computer-readable medium having computer-executable instructions stored thereon that, in response to execution by the at least one processor, cause the controller to perform operations including: manipulating, with the stressing device, the conformation of the first nucleic acid molecule from the first conformation to the second conformation, or from the second conformation to the first conformation; and manipulating, with the stressing device, the conformation of the second nucleic acid molecule from the first conformation to the second conformation, or from the second conformation to the first conformation.

[0092] In some aspects, the present disclosure provides a method comprising: storing logic data in a nucleic acid memory system by modulating a conformation of a nucleic acid molecule therein between (i) a first conformation and a second conformation, or (ii) the second conformation and the first conformation, the nucleic acid memory system comprising: the nucleic acid molecule, comprising a first end and a second end; a first electrically conductive contact coupled to a first end of the nucleic acid molecule; and a second electrically conductive contact coupled to a second end of the nucleic acid molecule; and retrieving the logic data from the nucleic acid memory system by measuring, with a conductance measurement device coupled to the first and second ends of the nucleic acid molecule, a conductance value across the nucleic acid molecule. In some embodiments, the nucleic acid memory system is an example of any of the nucleic acid memory systems described herein.

[0093] In this regard, FIGURE 7 depicts a flow chart of a method in accordance with the present disclosure. Block 302 depicts a storing logic data step, and block 304 depicts a retrieving logic data step. Blocks 302 and 304 each include a number of optional operations that may occur independently for each memory device of a memory system. For instance, block 302 includes: block 306 manipulating a first nucleic acid from a first to a second conformation; block 308 manipulating a second nucleic acid from first to secondconformation; block 310 manipulating a first nucleic acid from a second to first conformation; or block 312 manipulating a second nucleic acid from a second to a first conformation. Block 304 relates to the retrieving of logic data stores by the conformational changes to the memory system, and accordingly includes: block 314 measuring a first conductance state of first nucleic acid in first conformation; block 316 measuring a second conductance state of a first nucleic acid in a second conformation; block 318 measuring a first conductance state of a second nucleic acid in a first conformation; and block 320 measuring a second conductance state of a second nucleic acid in a second conformation. One of ordinary skill in the art would understand that any of the individual process steps described in FIGURE 7 may be performed in any order, and for any memory device of a memory system or memory array. Additionally, any process step may be performed repeatedly or reversibly depending on whether data is being written, rewritten, erased, or retrieved, in accordance with any of the embodiments of the present disclosure.

[0094] For instance, if a memory device of a memory system is acting as a memory element, then the encoding of data is performed by conformation manipulation of the nucleic acid molecules, while retrieval of data is done by applying a small bias to the memory device of the memory system. The application of a smaller bias may not induce any conformational change in the system.

[0095] As another instance, if a memory device of a memory system is acting as a logic device, then there is no storage or retrieval step; instead, the memory system will act as a non-linear or linear resistance with resistivity being dependent on the conformation of the nucleic acid molecule. Additionally, an ssRNA-based transistor or an ssRNA-based switch may be built using a third terminal.

[0096] In some aspects, the present disclosure provides a non-transitory machine-readable storage medium having instructions stored thereon, which when executed by a processing system, cause the processing system to perform a method comprising: storing logic data in a nucleic acid memory system by modulating a conformation of a nucleic acid molecule therein between (i) a first conformation and a second conformation, or (ii) the second conformation and the first conformation, the nucleic acid memory system comprising: the nucleic acid molecule, comprising a first end and a second end; a first electrically conductive contact coupled to a first end of the nucleic acid molecule; and a second electrically conductive contact coupled to a second end of the nucleic acid molecule; and retrieving the logic data from the nucleic acid memory system by measuring,with a conductance measurement device coupled to the first and second ends of the nucleic acid molecule, a conductance value across the nucleic acid molecule. In some embodiments, the nucleic acid memory system is an example of any of the nucleic acid memory systems described herein.EXPERIMENTAL METHODS

[0097] The following method steps are provided by way of example. It will be apparent to one skilled in the art, however, that the examples and methods disclosed herein may be practiced without embodying all the specific details. In some instances, well-known process steps have not been described in detail in order not to unnecessarily obscure various aspects of the present disclosure. Further, it will be appreciated that examples and methods of the present disclosure may employ any combination of features described herein MOLECULAR DYNAMICS SIMULATION SETUP

[0098] The structures of both ssRNA and dsRNA were created with Nucleic Acid Builder (NAB). The ssRNA sequence is: 5’ - GGGGGCGGGG - 3 ’ (SEQ ID NO: 1) while the dsRNA sequence is: 5’ - GGGGGCGGGG - 3’ / 3’ - CCCCCGCCCC - 5’ (SEQ ID NO: 2). All Molecular Dynamics (MD) simulations were performed in AMBER 20 software with explicit solvent. An RNA OL3 force field was used with TIP3P for water.

[0099] Firstly, a two-step minimization was performed on the generated structures. In the first stage, the solvent was relaxed with counterions by applying a restraint of 50 kcal / mol force on ssRNA / dsRNA. The minimization step involves 5000 steps with 250 cycles of steepest descent and rest with conjugate gradient descent with the non-bonded cutoff of 10 A. After solvent / counterions are minimized, energy minimization was performed on the whole system during the second stage, with the same recipe as the first one.

[0100] Secondly, the system was heated from 0 to 300 K in a span of 1 ns. The temperature was increased linearly in 5000 steps and then kept constant for the rest of the simulations. For temperature control, the Langevin thermostat with a 1 ps-1collision frequency was adopted. SHAKE algorithm was activated to constrain bonds involving hydrogen atoms with a convergence tolerance of 10-5. Initial velocities were also randomized. During the heating stage, the NVT ensemble (constant volume) was considered with ssRNA / dsRNA restrained with a force of 50 kcal / mol. Following up, equilibration was performed for 1 ns on the structures and velocities obtained from the previous heating stage. During this step, the target temperature was maintained at 300 Kwith a Langevin thermostat with 1 ps-1collision frequency but reduced force restraint of 0.5 kcal / mol on ssRNA / dsRNA to allow structural relaxation.

[0101] Finally, the production stage was carried out with the final structures and velocities obtained from the equilibration step under the NPT ensemble. For both ssRNA / dsRNA, the production step lasted for 200 ns. Like the previous stages, the SHAKE algorithm and Langevin thermostat were activated. The non-bonded interaction cutoff was set at 10 A. The Particle Mesh Ewald (PME) method was used to account for long-range electrostatic interactions.MOLECULAR DYNAMICS DATA ANALYSIS

[0102] To explore the structural stability of ssRNA / dsRNA, the following metrics were computed based on the MD trajectory: (i) ID- and 2D-RMSD (ii) End-to-end phosphorous distance (ΔPdis) (iii) Hydrogen bonding heatmaps and (iv) Backbone Dihedral angles. All the MD data analyses were performed with Cpptraj and Pytraj packages. Detailed descriptions of these metrics are as follows:

[0103] ID- and 2D-RMSD: Pairwise RMSD of the trajectory was computed with pairwise rmsd module in Pytraj.1D-RMSD was derived from the first row of the 2D-RMSD matrix.

[0104] End-to-end phosphorous distance (APdis): The distance between phosphorous (P) atoms of the 2ndand 10thresidues was calculated using the distance module of Pytraj.

[0105] Hydrogen bonding heatmaps: Hydrogen bonding was computed using the hbond function of Cpptraj by considering each residue as both a donormask and an acceptormask. The hydrogen bonds are detected based on the criteria: angle cutoff of 135° and distance cutoff of 3 A. The heatmaps were generated from the average number of hydrogen bonds between any two residues and between the base and backbone over a 200 ns trajectory.

[0106] Backbone dihedral angles: The six backbone dihedral angles (a, p, y, S, e, ) were extracted along with the angle. The definitions of these angles are as follows:[a: O3'(i — 1) — P — 05' — C5'][ -. P - 05' - C5’ - C4'][y: 05' — C5' — C4' — C3'][<5: C5' — C4' — C3' — 03'][e: C4' - C3' - O3' - P(i + 1)][<: C3’ - 03’ - P(i + 1) - O5'(i + 1)][y for pyrimidines: 04' — Cl' — N1 — C2][X for purines: 04' — Cl' — N9 — C4]where, (i + 1) and (i — 1) represent the next and previous residues.

[0107] Additionally, in salt concentration analysis, the rdf module of Pytraj was used to compute the radial distribution function with a bin size of 0.01 A.FRAME SELECTION PROCEDURE

[0108] ssRNA: 100,000 conformations (frames) were derived from the MD simulations of ssRNA, and frame selection from this vast dataset involved a two-step process.

[0109] Firstly, all conformations were classified into multiple categories based on end-to-end phosphorous distance (ΔPdis), a parameter that reflects the proximity of the terminal bases and, by extension, the folding or unfolding state of the conformation. To capture the full spectrum of ssRNA conformational states, five categories of ΔPdiswere considered. However, each category contained hundreds of conformations making it computationally expensive to perform DFT / transport calculations on each of them.

[0110] Hence, in the second step, frame selection was refined by considering the number of stacked bases such that the impact of base positioning on charge transport was included. The bases were considered to be stacked when they satisfy the three following conditions:(ii) Pjk< 2.5 A and(iii) |αjk| < 40°,where ρjk= x²jk+ y²jkand (Xjk, yjk, Zjk) are distances between the center of masses of the two bases (j, k) along the x-,y-, and z-axis. αjkis the angle between normal vectors of bases.k.

[0111] In each category, the conformations were classified into sub-categories based on number of stacked bases, which typically range from 2 to 7. From each of these sub-categories with the same number of stacked bases and almost similar ΔPdis, conformations were sorted based on the sum of all angles (2 between normal vectors of adjacent bases (<z). A set of five frames per sub-category, representative of minimum,maximum, median, 1st’ and 3rdquartile values of the sum of angles (£ cr), were chosen. This yielded a total of 125 conformations.

[0112] dsRNA: The abovementioned frame selection procedure is not required for dsRNA as it exhibits significantly greater stability with minimal variation in Pdis. Thus, clustering was performed with VMD software and the head of the cluster chosen for the top five clusters, which accounts for > 95% of the population.

[0113] It is to be noted that all the selected conformations of both ssRNA and dsRNA undergo a two-step energy minimization process in AMBER 20 before charge transport calculations are performed. In the first step, the solvent and counterions are minimized over 2500 steps with restraint on ssRNA / dsRNA, while during the second step, the whole system undergoes energy minimization for 2500 steps. These energy-minimized structures are used for DFT / transport calculations.AB-INITIO DFT MODELING

[0114] Density functional theory (DFT) calculations have been performed in the Gaussian 16 software package with Gaussian-type orbitals. The hybrid functional B3LYP with a 6-31G** basis set has been used. To incorporate the solvent effect (water in this case), the polarizable continuum model (PCM) has been included. For all self-consistent field (SCF) calculations, the default “tight” convergence criteria of Gaussian were used. Following this, the Fock (F) and Overlap (5) matrices were extracted using readmat utility.

[0115] To operate with an orthogonal atomic basis set, the Hamiltonian (H) of the system was generated from Fock (F) and Overlap (S) matrices by performing Lowdin transformation as follows:1 1H = S-½FS-½(1)

[0116] The diagonal terms in H represent the onsite energies of the orbitals, while off-diagonal terms correspond to the hopping energy between orbitals. For the transport calculations, the whole Hamiltonian was partitioned based on individual bases.

[0117] In this approach, the Hamiltonian was rearranged in the following way to obtain a modified Hamiltonian (HI):where, HIkk(where k ∈ [1,10]) represents the sub-Hamiltonian matrix corresponding to base k.

[0118] The diagonal / off-diagonal elements within HIkkdescribe the onsite potentials of all atomic orbitals in base k and hopping energy between those orbitals respectively. The off-diagonal blocks HIkk'(where k ≠ k'; k,k' ∈ [1,10]) indicate the hopping energies between orbitals in base k and k'. The dimension of HIkkiswhere bj is the total number of basis sets used to represent atom j in base k and Nkis the total number of atoms in base k.

[0119] Next, a unitary transformation was applied to HIto obtain the final Hamiltonian (HDNA), which was used in the transport calculation. The transformation is expressed as follows:HDNA= U†HIU (3)

[0120] The unitary matrix U is defined as:where ukis a diagonal sub-matrix containing the eigenvectors of HIkk.TRANSPORT CALCULATIONS

[0121] For charge transport calculations, firstly, the retarded Green’s function (Gr) was computed, including self-energies of contacts and decoherence probes as follows:[E - HDNA- ΣL- ΣR- ΣB(E)]Gr= I (5) where E is the energy, ΣL(R)(= - ^) are the self-energies due to left (right) contacts while ΓL(R)represent the corresponding coupling between DNA and left(right) contacts. ΣBdepicts combined self-energies of decoherence probes.

[0122] Energy-dependent decoherence probes have been considered, which is an improvement over the energy-independent model. For an energy-dependent decoherence probe, the imaginary part of ΣBis expressed as:where, Vkmrepresents the coupling between the decoherence probe and molecular orbital m in base k. Regarding left / right contact self-energies, the wide-band limit has been considered in which

[0123] For all calculations, the following values of parameters have been chosen: ΓL= ΓR= 0.1 eV; ΓB= 0.1 eV; η = 0.1 eV. All atoms in bases 7 and 10 are connected to left and right contact respectively. The effective transmission is expressed as:NbNbTeff= TLR+TLk Wkl TlR (7)k=l 1=1where, TLRrepresents the coherent transmission between the left and right electrodes. The second term accounts for the contribution to transmission via the decoherence probes. The transmission function between probes k and I is given by Tkl= ΓkGrΓlGa(k ∈ [1, N]). Ga= (Gr)+is the advanced Green’s function. The termis the inverse of Wkl-1where Rkkis the reflection probability at probe k, calculated asLINEAR RESPONSE CONDUCTANCE

[0124] The zero-bias or linear response conductance is computed from the effective transmission with the following equation:G = (2e² / h) ∫ Teff(E) (-∂f / ∂E) dE (8) [Fermi-Dirac distribution]DENSITY OF STATES CALCULATION

[0125] The density of states calculation involves no contact self-energies. Avery small broadening (η = 0.001) was considered. Like transport calculations, the retarded Green’s Function was calculated:

[0126] The local density of states (LDOS) at an energy point is calculated by solving the following equation:WAVEFUNCTION PROJECTION:

[0127] To compute the probability (|Ψ|2) of finding an electron on each base at any energy level, the projected wavefunction of that energy on each base has been computed. First, the following eigenvalue problem was solved with Fock (F) and Overlap (S) matrices:FV = SE (11)where E is the list of eigenvalues corresponding to allowed energy levels in the system and is the eigenvector whose mthcolumn corresponds to mthmolecular orbitals. The dimension of is the same as that of Fock (F).

[0128] To find the contribution of each base, the whole system was divided into base-wise fragments. Set of all wavefunctions pertaining to orbitals in a fragment is represented by Ψk(k ∈ [1,10]). The contribution of kthbase is computed as follows:where, Skk'represents the sub-matrix in the Overlap matrix which corresponds to orbitals in base k and k'. The first component represents the contribution due to the orbitals in the same fragment while the last two components correspond to overlap with other fragments. EXAMPLES EXAMPLE 1: MOLECULAR DYNAMICS RESULTS: SSRNA VS DSRNA

[0129] The 10-base ssRNA sequence 5’-GGGGGCGGGG-3’ (5’-G5CG4-3’; SEQ ID NO: 1) was selected to investigate conductance variability induced by folding and unfolding phenomena. A 10-base pair dsRNA structure comprising the complementary sequence of the ssRNA, 5’-G5CG4-373’-C5GC4-5’ (SEQ ID NO: 2) was also considered. In this regard, SEQ ID NOS: 1 and 2 are examples of the nucleic acid molecule of a nucleic acid memory device according to aspects of the present disclosure. Molecular dynamics (MD) simulations were conducted for 200 ns on both structures (as described herein above under Methods), with frames captured every 2 ps, yielding a total of 100,000 conformations.

[0130] A comparative evaluation of the structural stability of ssRNA and dsRNA is presented in FIGURE 1 A to FIGURE IE. The root mean square deviations (1D-RMSD), calculated relative to the initial frame, are shown in FIGURE 1 A, where it is evident that dsRNA exhibits greater structural stability than ssRNA, with an average RMSD of 1.95 ± 0.52 A, compared to 5.60 ± 1.15 A for ssRNA.

[0131] This trend is further corroborated by the 2D-RMSD plots shown in FIGURE IB. While ID RMSD provides a reasonable estimate for structural stability, the 2D-RMSD heatmaps highlight the presence / absence of multiple low RMSD regions or stable conformation states. For ssRNA (FIGURE IB, left), six distinct patches of low RMSD (< 5 A) were identified. Among these, the biggest patch is approximately between 85-150 ns.

[0132] On the contrary, the 2D-RMSD heatmap of dsRNA (FIGURE IB, right) has a maximum value of 5.75 A, significantly lower than the 13.32 A observed for ssRNA. This results in the absence of low RMSD “patches” in dsRNA, underscoring its “stability throughout the MD trajectory”

[0133] To gain deeper insight into the conformational dynamics of both ssRNA and dsRNA, end-to-end phosphorus distance (ΔPdis) was employed, defined as the distance between 1stand 9thphosphorus atoms, as a metric for analysis. The value of. Pdisis directly proportional to the bending of the backbone. From FIGURE 1C, it was observed that in the case of ssRNA, ΔPdisvaries considerably (unlike dsRNA, shown in the right panel of FIGURE 1C), spanning a range from 6.40 to 47.18 A, with an average value of 21 A. This average value was used to classify the conformations into folded (ΔPdis< 21 A) and unfolded (ΔPdis≥ 21 Å) states, yielding a folding probability of 47.88% (i.e., 47880 out of 100,000 conformations have Pdis< 21 Å ).

[0134] When correlating ΔPdisvalues with low RMSD patches in the 2D-RMSD heatmap, the ssRNA sequence exhibits stable configurations in both folded and unfolded states. For instance, for the low RMSD patches between « 20-40 ns and « 85-150 ns in FIGURE IB, left panel, the ssRNA sequence has a Pdisvalue of less than 21 A. For other low RMSD patches,ΔPdisis relatively higher, suggesting shuffling between the folded and unfolded states. In contrast, dsRNA exhibits a tighter distribution of Pdis(see FIGURE IC, right), ranging from 21.72 to 36.48 A with a mean value of 28.4 A which is consistent with the trends in RMSD plots in FIGURE 1A and FIGURE IB. For dsRNA, two distributions of. Pdisfor 5’-3’ and 3’-5’ strands were obtained, which are very similar to each other; in FIGURE 1C, bottom panel, the mean Pdisis shown over both strands.

[0135] The distributions of the seven backbone dihedral angles were analyzed to further characterize the structural fluctuations of ssRNA and dsRNA, as shown in FIGURE ID. It is evident that the coefficient of variation (CV) of all dihedral angles, derived from 100,000 conformations, are considerably higher for ssRNA than dsRNA, which is consistent with RMSDs andΔPdisvalues shown in FIGURE 1 A, IB, and 1C. In particular, the CV of the dihedral angle between bases and backbone (x) for ssRNA is 51.6% higher compared to dsRNA.

[0136] To further probe the backbone dihedral distributions, the residue-wise time evolutions of backbone dihedrals for ssRNA and dsRNA were examined. For dsRNA, the dihedrals are extremely stable with minimal fluctuations, consistent with the 2D RMSDheatmap in FIGURE IB. In contrast, ssRNA demonstrates pronounced fluctuations in its backbone dihedrals. Specifically, the 3’-end residues’ dihedrals (primarily a, 6, <() show significant perturbation between « 20-200 ns. Minor variations in the interior residue dihedrals from « 80 ns coincide with the onset of ssRNA folding ( ΔPdis< 21 Å, FIGURE 1C, top). These dihedrals’ perturbations are attributed to the interior bases to the folding of the structure. Without wishing to be bound by any particular theory, this may be triggered by fluttering of the 3 ’-end residues. A comparative analysis of probability densities for all dihedral angles reveals, in general, the pdfs of ssRNA are multimodal, in contrast to unimodal for dsRNA (with the exception of β). While the locations of the primary peaks for ssRNA align closely with those for dsRNA, the secondary peaks for ssRNA can be attributed to folding-induced dihedral perturbations.

[0137] To further elucidate the underlying reasons for structural dynamics, hydrogen bonding between different residues are compared. Considering each nucleotide as both a donor and an acceptor for hydrogen bonding, heatmaps with the average number of hydrogen bonds are presented in FIGURE IE, which highlights two distinct types of hydrogen bonds: (i) intra-nucleotide hydrogen bonds, formed between atoms in the backbone and base of the same nucleotide (represented by the main diagonal elements) and (ii) inter-nucleotide hydrogen bonds, formed between backbone and base of one nucleotide and those of another nucleotide.

[0138] Inter-nucleotide hydrogen bonds can be further subdivided into two categories: bonds between adjacent nucleotides (depicted by elements on the upper and lower diagonals in FIGURE IE), and those between non-adjacent nucleotides (represented by all other elements except those on the main, sub, and super diagonals). The presence of hydrogen bonds between adjacent bases indicates stabilization of the ssRNA, while bonds between non-adjacent bases suggest a higher likelihood of folding. Intra-nucleotide hydrogen bonds occur only when the nucleotide comes close to the backbone during the MD trajectory.

[0139] FIGURE IE supports three conclusions. First, in the case of ssRNA (FIGURE IE, top), a significant number of hydrogen bonds are observed between adjacent bases (elements on sub and super-diagonals) as well as non-adjacent bases, such as those between bases 9 & 3, 1 & 10, and 4 & 8. The former (latter) type of bonding explains the stability of the unfolded (folded) conformations. Second, intra-nucleotide hydrogen bonding is considerably higher for the terminal nucleotides (1 and 10), which can beattributed to the twisting of the nucleotide, bringing it in proximity to the backbone and allowing hydrogen bonds to form between the backbone and base. However, the occurrence of such twisting is less likely in the non-terminal bases, resulting in low hydrogen bonds along other diagonal elements in FIGURE IE, top. Finally, in dsRNA (FIGURE IE, bottom), it is evident that hydrogen bonds within a base pair dominate those between adjacent base pairs. This explains the tight distribution of Pdisfor dsRNA in FIGURE 1C, bottom.EXAMPLE 2: CONDUCTANCE VARIATIONS IN SSRNA

[0140] In FIGURE 1, the structural instability associated with ssRNA was discussed. In this section, the impact of structural instability on the conductance of ssRNA is analyzed. Toward that end, the 100,000 ssRNA conformations are classified into five distinct categories based on ΔPdisvalues, namely, 10 Å to 30 Å in steps of 5 A with a tolerance of 10% (i.e., the nominal ΔPdisvalues for the five categories are 10, 15, 20, 25, and 30 A). From each category, frames based on the number of stacked bases are chosen, leading to a total of 123 selected conformations. The detailed frame selection methodologies for both ssRNA and dsRNA are provided herein under the Methods.

[0141] Typical representations of the backbone orientations for the five Pdiscategories from 10 A to 30 A are shown in FIGURE 2 A. Energy-dependent decoherence probe-based charge transport calculations were performed (details available in Methods) on the selected structures with the contacts connected to the first and last bases. The zerobias conductance of each selected conformation with the Fermi energy corresponding to the HOMO energy was determined. These conductance values are shown as a function of time in FIGURE 2B, left.

[0142] To better illustrate the conductance dispersion, the probability density function (PDF) is shown in FIGURE 2B, right. The mean and standard deviation of the PDF of log10(G / Go) are obtained to be -4.68 and 2.02, respectively, where G and Goare the ssRNA conductance and quantum of conductance respectively. The high standard deviation suggests that conductance variability is closely related to conformational fluctuations. The pronounced conductance stochasticity observed in ssRNA is attributed to its ability to exhibit multiple metastable states, unlike the well-characterized dsDNA, which generally remains unfolded and exhibits a narrow conductance distribution - as supported by the dsRNA conductance data presented in the present disclosure (see TABLE 1).

[0143] Table 1: dsRNA Conductance data

[0144] Next, to explore the dependence of conductance dispersion on Pdts, the conductance distributions of conformations for each category of PdiSare presented in FIGURE 8. The average conductance decreases from folded (ΔPdis= 10, 15 A) to unfolded (ΔPdis= 25, 30 Å) states. Overall, it can be inferred that folding, in general, leads to an increase in conductance along with lesser variability, a property which can be leveraged for next-generation synthetic-biology-based electronics. Accordingly, in some embodiments, this folded state may represent a first conformation of the nucleic acid molecule, and the unfolded state may represent a second conformation of the nucleic acid molecule. In this regard, these experiments demonstrate that, in some embodiments, a nucleic acid in a folded state (the first conformation) has a conductance that is larger in magnitude than a conductance of the nucleic acid in an unfolded state (the second conformation). However, it should be understood that in some embodiments, this relationship may be reversed, and the nucleic acid in the folded state may have a conductance that is smaller in magnitude than the nucleic acid in the unfolded state.EXAMPLE 3: ELECTRONIC PROPERTIES OF CONFORMATIONS

[0145] A striking observation across all categories in FIGURE 2B is the substantial disparity between the maximum and minimum conductance values observed among the conformations. The corresponding extreme conductance values for all five Pdiscategories are provided in Table 2. For every Pdiscategory, the conductance spread (defined as the ratio of maximum to minimum conductance in a category) was found to range between « 103-106Go, which is substantial and highlights the significant influence of conformation in determining conductance. To unravel the impact of conformation on conductance, the extreme conductance cases were studied, low conductance conformation (LCC) and high conductance conformation (HCC) of Pdis= 15, 20, and 25 A. For aholistic understanding of conductance fluctuations, and without wishing to be bound by any particular theory, the conformations were compared based on four metrics.

[0146] Table 2: Summary of Lowest and Highest Conductance values in each category of Pdis.LCC: Lowest conductance conformationHCC: Highest conductance conformationGo: Quantum conductance = 7.748 X 10-5S

[0147] First, the structural differences between LCCs / HCCs of each category in FIGURE 3 A to FIGURE 3C were analyzed. For PdiS= 15 A, the distance between 3’ and 5’ ends is lower for HCC in contrast to LCC (see FIGURE 3 A). Quantitatively, the distance between the center of masses of terminal bases 1 and lOis 10.13 A (8.41 A) for LCC (HCC).This distinction becomes more pronounced for Pdis= 20 A (FIGURE 3B), where the separation between the terminal bases is 23.02 A for LCC vs. 13.31 A for HCC. Moreover, unlike the LCC structure, the 5’ end in HCC is close to the 7thand 8thbases (6.68 A and 7.65 A respectively). A similar trend can be noticed for APdis= 25 A. (FIGURE 3C). In this case, the distances between the terminal bases are 28.63 A and 24.87 A for LCC and HCC respectively. These results, combined with the conductance data provided in Table 2, suggest that the distance between terminal bases and conductance should be correlated.Intuitively, this is justified since a lower terminal base distance decreases the hopping length, leading to higher conductance.

[0148] However, the inter-terminal base distance alone cannot completely account for the substantial conductance ratio between LCCs and HCCs. To further address this issue, a second metric, delocalization of HOMO and HOMO-1 orbitals among the bases was considered. A higher delocalization suggests better orbital overlapping between the bases, which in turn is indicative of better charge transport. For the three specific cases depicted in FIGURE 3 A to FIGURE 3C, the proximity of bases plays a role in orbital delocalization, for both folded and unfolded configurations. For APdis= 15 A, a closerobservation reveals that the 1stbase has moved closer to the 10thbase in HCC, whereas in LCC it swings away. Consequently, the HOMO orbital is delocalized over bases 1,7,8,9,10 for HCC, while it is delocalized only over bases 3, 4, 5, 6 for LCC. The HOMO-1 orbital is also delocalized for HCC, but over bases 2, 3, 4, 5, whereas for LCC, it remains delocalized on bases 2,3,4. Similarly, for Pdis= 25 A, a delocalization over bases 1 to 8 for HCC was observed. In contrast, the proximity of 3’ terminal bases (8,9,10) for LCC leads to strong orbital overlap, causing the HOMO orbital to localize near the 3’ terminal. The trends of high delocalization for HCC become more evident for the HOMO-1 orbital.

[0149] Interestingly, for APdis= 20 A, although the inter-base distances are lower in HCC than LCC (FIGURE 3B), the HOMO orbital delocalization is more pronounced for LCC (over bases 1,2, 3, 4, 5) than HCC (over bases 8,9,10). However, it was found that the HOMO-1 orbital is more delocalized for HCC than LCC. To quantify orbital localization, thecomputed, where |Ψi|2is the probability of finding an electron at the itflresidue). The greater the value of IPR (maximum value is 1), the greater is the orbital localization.

[0150] The corresponding probabilities (I'Pj |2) are shown in FIGURE 9A to FIGURE 9E. The IPR values of LCC and HCC at corresponding HOMO (HOMO-1) energies are 0.85 (LOO) and 1.00 (0.72) for £ Pdis= 20 A. Additionally, the HOMO & HOMO-1 levels differ by 150 meV (« 5fcBT) and 20 meV ( < « kBT) respectively for LCC and HCC.

[0151] This suggests that when the Fermi energy is near the HOMO level for HCC, both HOMO and HOMO-1 orbitals can participate in electronic transport due to their relatively small energy separation. Therefore, it was concluded that for the Pdts= 20 A category, small energy differences between the first few HOMOs, coupled with strong orbital delocalization, results in higher conductance of HCC. The trend of energetically close HOMOs with lower IPR values for HCCs relative to LCCs is also applicable for the other two categories ( PdiS= 15 and 25 A).

[0152] From the preceding discussions, two observations were made: (i) while higher delocalization is typically indicative of better charge transport, conductivity is ultimately governed by the intricate interplay between inter-base distances and the extent of orbital delocalization, and (ii) although conductance is calculated with the Fermi energy at the HOMO energy level, to fully comprehend the underlying electrostatics, the energy differences among the first few HOMO energies are analyzed. This additional analysisprovides a more complete picture of how orbital characteristics and their variations impact charge transport in ssRNA. These observations also extend to Pdts=10 and 30 A categories (not illustrated).

[0153] Next, the conductance trends were analyzed based on density of states of the conformations. The 2D DOS heatmaps are shown in FIGURE 4A to FIGURE 4C, top row. It is noted that the lower delocalization in HCC for APdis= 20 A is also reflected in the base-wise PDOS (see FIGURE 4B), causing the total DOS at HOMO of the LCC to be higher than that of the HCC. Further into the HOMO band, even a small shift of 10 meV results in the total DOS as well as base-wise partial DOS of HCC to surpass those for LCC.

[0154] Without wishing to be bound by any particular theory, this explains the high conductance of the HCC. For the other two categories, Pdts=15 and 25 A, the total DOS of HCCs at HOMO is substantially larger than corresponding LCCs, a trend that holds for other energies close to HOMO. Additionally, it was observed from FIGURE 4A to FIGURE 4C, top row, that for all Pdtscategories, high DOS patches are concentrated near or at HOMO for the HCC. These high DOS energy levels primarily contribute to charge transport, resulting in a high transmission probability for HCCs at HOMO energy level (FIGURE 4A to FIGURE 4C, bottom row).

[0155] From the transmission profiles across different Pdts, two observations are made: (i) For both LCC and HCC, the transmission at HOMO energy drops with increase in Pdts,. This finding also holds for APdis= 10 and 30 A. (ii) The transmission in the bandgap is considerably higher for folded (ΔPdis= 10 and 15 A) states in contrast to unfolded ( Pdis= 25 and 30 A) states. At lower APdis, the tunneling probability between terminal bases is higher due to their proximity, while at higher ^PdiS, transport is more dependent on hopping between bases. Given that tunneling between terminal bases serves as a promising transport mechanism, conformations in folded states result in higher transmission in the bandgap, despite having negligible DOS.

[0156] The conductance of ssRNA depends primarily on the efficiency of carrier transport between the two contacts, which are bases 1 and 10 in the simulation setup. The three charge transport properties discussed - inter-base distance, orbital delocalization, and density of states - individually highlight the underlying reasons for significantly higher conductance (see last row in Table 2) in HCC over LCC across all Pdiscategories. However, to comprehensively understand the rationale behind the high conductance ratio between HCC and LCC, a fourth metric was devised, probable pathways, comprising fourcomponents: (i) inter-base distance (ii) total DOS (iii) orbital overlap, and (iv) length of a path (number of nodes).EXAMPLE 4: HARNESSING CONFORMATIONAL FLUCTUATIONS OF SSRNA

[0157] From an applications perspective, the high stochasticity in ssRNA conductance observed in FIGURE 2A and FIGURE 2B is undesirable. As demonstrated previously, the underlying reason for this variability is structural instability. Taking a cue from previous studies which have shown that salt concentration plays a vital role in stabilizing RNA conformations, low (~ 100 mM with 11 CF ions) and high (~ 450 mM with 41 CF ions) salt concentrations were considered in the calculations, as illustrated in FIGURE 5A to FIGURE 5E. Initially, this setup was validated by computing the radial distribution functions (RDF) for Na+ions relative to the phosphate group in ssRNA, as well as water molecules around Na+ions (hydration shell).

[0158] The 1D-RMSD in FIGURE 5A clearly demonstrates that the average RMSD decreases with an increase in salt concentration. Comparing the 2D RMSD heatmaps in FIGURE 5B with FIGURE IB, left, increasing the salt concentration leads to a reduction in overall structural fluctuations during the MD trajectory. This is evident from the increase in low RMSD patches as the salt concentration rises.

[0159] In FIGURE 5C, Paiswasplotted as a function of time for three different salt concentrations: (i) negligible (N, CF= 0), (ii) low (L, CF= 11), and (iii) high (H, CF = 41). Indeed, the folding of ssRNA, as quantified by Pais, has dropped from 47.88% in the “no salt” case to 36.89% and 23.44% for low and high salt concentrations respectively. The backbone structural stability is also reflected in a decreasing trend of the coefficient of variation (CV) of the six backbone dihedrals (a,?, y, <5, e, ) with increasing salt concentration (FIGURE 5D). A lower CV of the dihedral angle x, which signifies fluctuations of nitrogenous bases, attests to low conductance stochasticity.

[0160] Finally, the hydrogen bonding analysis in FIGURE 5E reveals the presence (absence) of more hydrogen bonds between adjacent (non-adjacent) bases at higher salt levels, explaining the increased stability of the ssRNA conformation. These observations suggest that increasing salt concentrations may be a viable approach to controlling structural fluctuations in ssRNA. This stabilization, in turn, reduces the variability in conductance, offering a more consistent performance. Such control overconductance spread can be strategically leveraged to develop ssRNA-based electronic devices, where reliable charge transport influences functionality.

[0161] Accordingly, in some embodiments, a memory system or memory array according to aspects of the present disclosure may include a stressing device, wherein the stressing device is configured to adjust a salt concentration of a solution comprising the memory system or memory array.EXAMPLE 5: MODULATING SSRNA FOLDING IN THE LAB

[0162] With alteration in the ssRNA folding state, the conductance of ssRNA will change. From an experimental point of view, the inter-electrode separation (ΔPdis) will be modulated to control the fol ding / unfol ding of ssRNA. FIGURE 10 provides an example of a memory system that will demonstrate a complete switching cycle.FIGURE 10 depicts a left contact (a first electrically conductive contact) which will be connected to a first end of a strand of ssRNA, and a right contact (a second electrically conductive contact) which will be connected to a second end of a strand of ssRNA. In some embodiments, the ssRNA, right contact, and left contact comprise a nucleic acid memory device. Time points A to E are depicted to represent the movement of the right contact, which will be modulated to increase the ssRNA folding state (i.e., to provide a more folded form of the ssRNA). While a single stranded nucleic acid molecule, such as ssRNA, is depicted in FIGURE 10 for clarity, it should be understood that nucleic acid memory device 100 may include other nucleic acid molecules, including single stranded DNA (ssDNA), double stranded DNA (dsDNA), or double stranded RNA (dsRNA). Additionally, other quantities of nucleic acids may be used, including triple stranded nucleic acids. It should be understood that these embodiments fall within the scope of the present disclosure.In this regard, in some embodiments, the movement of the right contact may be modulated by a controller operatively coupled to the nucleic acid memory device, the controller including at least one processor and a computer-readable medium having computer-executable instructions stored thereon that, in response to execution by the at least one processor, cause the controller to perform operations including: (i) measuring a first conductance state of the nucleic acid molecule in a first conformation of the two or more conformations, or (ii) measuring a second conductance state of the nucleic acid molecule in a second conformation of the two or more conformations, wherein the first conductance state is associated with a first logic state and the second conductance state is associated with a second logic state. Movement between first and second conductancestates may be performed by a stressing device, which may be configured to adjust a pH or a salt concentration of a solution comprising the nucleic acid memory device, or which may be a mechanical strain-inducing device configured to manipulate the conformation of the nucleic acid molecule, such as by using optical tweezers, magnetic tweezers, a piezoelectric device, or combinations thereof.

[0163] Time points E to I are depicted to represent the movement of the right contact, which will be modulated to decrease the ssRNA folding state (i.e., to provide a less folded form of the ssRNA).

[0164] Accordingly, the switching timescale will primarily be governed by the rate of right contact modulation in FIGURE 10; however, the precise switching time will also depend on the nucleotide arrangement for a fixed inter-electrode distance. It should also be understood that, while the terms “right” and “left” are used for clarity of description, any configuration of first and second contacts may be used and falls within the scope of the present disclosure. Additionally, while ssRNA is depicted in FIGURE 10, a similar principal will apply to a double-stranded nucleic acid molecule, such as dsDNA, or dsRNA. Moreover, while for illustrative purposes the ssRNA is depicted as a string, the nucleic acid molecules of the present disclosure may comprise between about 2 and about 100 base pairs, between about 5 and about 50 base pairs, between about 10 and about 25 base pairs, or about 10 base pairs.EXAMPLE 6: OPTIONS FOR FORMING CONTACT WITH SSRNA

[0165] The ssRNA conductance measurements will be carried out with either metallic or non-metallic (covalent) electrodes.

[0166] For instance, as depicted in FIGURE 11, contact options will include gold electrodes, carbon nanotube (CNT) electrodes, and piezo contacts on a bent substrate. Additionally, in some embodiments, the electrically conductive contacts comprise quasi-one-dimensional semiconducting wires, such as carbon nanotubes, doped boron nitride nanotubes, graphene nanoribbons, and metallo-intercalated DNA strands.

[0167] Gold electrodes are widely used in single-molecule conductance studies and will be readily adopted for ssRNA-memory technology according to methods known to those of ordinary skill in the art. (FIGURE 11, top panel). Gold electrodes have advantages including formation of highly conductive metallic contact and ease of fabrication.

[0168] However, it is established in the relevant art that metallic / non-metallic interfaces will often introduce large variability in experiments. To address this, non-metallic alternatives like carbon-nanotube (CNT) electrodes will be utilized (FIGURE 11, middle panel). Conductive pathways through single-molecule (DNA) have been shown when DNA is connected to a CNT contact due to higher n — n overlapping. This configuration will improve control over experimental consistency.

[0169] A third electrode configuration consists of piezo-contacts (FIGURE 11, bottom panel). The piezo-contact configuration will be used when fine control of folding state is desired, where the voltage applied to the piezo-contacts will allow for fine control of switching between folding configuration states.

[0170] In any of these three configurations, a third terminal may be added to the substrate. This third terminal will add another control knob in the experiments. The third terminal may help in two ways: (1) it will help control the level of current for a fixed configuration, and (2) the electrostatic force from the third terminal may also help reconfigure the structure.EXAMPLE 7: ADDITIONAL SSRNA EXAMPLES

[0171] The MD results for additional modified motifs (SEQ ID Nos: 1 - 14), along with the baseline, are summarized in Table 3.

[0172] Table 3: Summary of MD simulations for additional ssRNA sequences' SB: Single Barrier, DB: Double Barrier, ADB: Alternate Double Barrier, QB: Quadruple Barrier. A / C / U at the end of each ID represents ‘G’ from baseline is replaced by ‘ A’,’C’ and ‘U’ bases respectively.#Average Pdtsis mean over 100,000 (last 50,000) conformations.$Mean of total number of stacked bases over 100,000 (last 50,000) conformations with a tolerance of 5%.

[0173] The folding of a short ssRNA sequence depends on the stacking between the adjacent bases. Purines (guanine and adenine) are double-ring structures, while pyrimidines (cytosine and uracil) contain a single ring. Owing to their structural differences, the stacking between purine and pyrimidine is expected to be lower than that between two purines. However, the folding capability required for memory devices in accordance with the present disclosure is demonstrated for a variety of sequences demonstrated by systematic modification of GGG-GGGG-GGG, as displayed in Table 3.

[0174] Examples of the folding of the sequences displayed in Table 3 are depicted in FIGURE 12A to FIGURE 12C.

[0175] FIGURE 12A depicts the most probable structures obtained after clustering of each sequence are shown for adenine (i, ii, Hi, iv) base substitution, according to embodiments of the present disclosure. Various categories of barriers are shown, namely, single (i), double (ii), alternate double (Hi, and off-center double (iv). Corresponding sequences are mentioned at the top of each column.

[0176] FIGURE 12B depicts the most probable structures obtained after clustering of each sequence are shown for cytosine (i, ii, Hi, iv) base substitution, according to embodiments of the present disclosure. Various categories of barriers are shown, namely, single (i), double (ii), alternate double (Hi), and off-center double (iv). Corresponding sequences are mentioned at the top of each column.

[0177] FIGURE 12C depicts the most probable structures obtained after clustering of each sequence are shown for uracil (i, ii, Hi, iv) base substitution, according to embodiments of the present disclosure. Various categories of barriers are shown, namely, single (i), double (ii), alternate double (Hi, and off-center double (iv). Corresponding sequences are mentioned at the top of each column.DISCUSSION:

[0178] The present disclosure provides a systematic exploration of the charge transport properties of a short (10-base) single-stranded RNA (ssRNA), which is desirable for electronic applications. Although the present analysis focuses on a specific ssRNA sequence, it is anticipated that the present findings may be extended extend to any short ssRNA. Analysis included a comparison of the structural stability of single- and doublestranded RNAs (FIGURE 1 A to FIGURE IE). The comparison was made using three key metrics: ID and 2D RMSDs, end-to-end phosphorous distance (ΔPdis) and backbone dihedral angles. The analysis revealed that while dsRNA exhibits greater stability in all three aspects, ssRNA is characterized by large conformational fluctuations. The excellent stability of dsRNA can be attributed to the presence of intra-base pair hydrogen bonding which is absent in ssRNA (FIGURE IE).

[0179] Moreover, the hydrogen bonding heatmaps depict that ssRNA is stabilized primarily by hydrogen bonds between adjacent / non-adjacent bases in an unfolded / folded state. This demonstrates that in short ssRNA sequences, hydrogen bonding betweenadjacent bases plays a role in determining the folding probabilities, offering a potential design rule for manipulating ssRNA structures.

[0180] Next, using an MD-frame selection procedure based on stacked bases and Pdis, 123 frames were selected from the pool of 100,000 conformations to perform charge transport calculations (FIGURE 2A and FIGURE 2B). It is noted that although state-of-the-art sampling methods (e.g., umbrella sampling, metadynamics, and adaptive sampling) exist which aim to achieve adequate conformational sampling while minimizing the computational cost, the present frame selection procedure proved adequate to capture conformations with a wide conductance spread. S. Chandra et al. Single-molecule conductance of double-stranded RNA oligonucleotides. Nanoscale 14, 2572-2577 (2022), performed STM-BJ-based conductance measurements of dsRNA and DNA: RNA hybrid, each 11 bp long with a poly-GC sequence and reported a conductance of « 1.63 X 10-3G0. More recently, S. Chandra et al., Charge transport in individual short base stacked single -stranded RNA molecules. Sci Rep 13, 19858 (2023 have also reported the conductance of 5-mer and 10-mer ssRNA to be « 2.9 — 3.6 X 10-3G0.

[0181] Table 4: Comparison of single-molecule conductances1. Chandra, S. et al. Single-molecule conductance of double-stranded RNA oligonucleotides. Nanoscale 14, 2572-2577 (2022).2. M. R. Aguilar, J. Jover, E. Ruiz, A. C. Aragones, J. M. Artes Vivancos, SingleMolecule Electrical Conductance in Z-form DNA: RNA. Small 2025, 21, 2408459. https: / / doi.org / 10.1002 / smll.2024084593. Chandra, S. et al. Charge transport in individual short base stacked single-stranded RNA molecules. Sci Rep 13, 19858 (2023).

[0182] Table 4 compares the single-molecule conductances of this work to the previously reported studies. Comparing the PDF in FIGURE 2B, right, to the previously reported conductance data, it was observed that the experimental conductance values are within one standard deviation of the mean computational conductance. The higher standard deviation is due to the consideration of diverse configurations, which are likely nonexistent in the break-junction experiments. The present disclosure highlights the impact of conformational fluctuations on ssRNA conductance. This involves sampling a broad range of configurations.

[0183] The significant spread of the conductance spectrum points towards the strong influence of conformational fluctuations on ssRNA charge transport. While conductance tends to increase with lower Pais, the wide spread of conductances across all Pdiscategories underscores the role played by nucleotide positioning. To probe the cause of drastic conductance disparities between two conformations with similar Pcus, a detailedquantum mechanical analysis was conducted on the extreme conductance conformations and observed a strong connection between the inverse participation ratio (IPR) for first few HOMOs and conductance (FIGURE 3). Moreover, it was established that the energy differences among first few HOMOs is considerably lower in high conductance conformations (HCC) over low conductance (LCC) ones. For HCCs, with Fermi energy at HOMO level, multiple HOMO energies can partake in electronic transport. However, in certain conformations, such as when £. Pdis= 20 A, inter-base distance dominates other electronic properties in determining ssRNA conductivity since shorter hopping distances facilitate more efficient carrier transfer between bases. This observation is corroborated by the transmission profiles shown in FIGURE 4A to FIGURE 4C (bottom).

[0184] A higher transmission probability in the bandgap for a folded configuration suggests that the transport mechanism is dominated by direct tunneling between terminal bases. With no prospect of such tunneling in an unfolded state, transmission drops significantly. These observations demonstrate that while / Pdisis a global factor which influences ssRNA conductance, inter-base distances enable local modulation of charge transport.

[0185] To substantiate this, a probable pathways metric was proposed for carrier transport based on path length, electronic properties, and inter-base distances. These pathways can offer valuable insight into the mechanisms which induce differences in conductance among conformations. Efficient charge transport favors shorter hopping distances and higher availability of states in the hopping sites. It was observed that while pathways in folded structures are governed largely by inter-base distances, those in unfolded structures depend on orbital delocalization and density of states. Finally, practical approaches to harnessing ssRNA structural fluctuations and reducing conductance stochasticity were explored. In FIGURE 5A to FIGURE 5E, it was demonstrated that higher salt concentrations stabilize ssRNA, as reflected in multiple structural attributes.

[0186] The present disclosure highlights that significant conductance contrast is possible on a nano-second timescale. The presence of electrodes alters the structural dynamics of a single-molecule by reducing the conformational fluctuations, resulting in a smaller ensemble of molecular configurations, is the present disclosure focused, at least in part, on unraveling the structural changes in single-molecule conductance, a wide range of configurations were considered.

[0187] These findings demonstrate that two distinct conductance states may be achieved through controlled manipulation of ssRNA unfolding and refolding. In this regard, state-of-the-art techniques such as optical and magnetic tweezers may be used to reversibly switch ssRNA between these two conformational states.

[0188] When combined with a conductance measurement setup, this approach provides the basis for ssRNA-based ultra-scaled memory devices and switches. Additionally, regulating salt concentrations offers a viable strategy to limit conformational fluctuations, ensuring more deterministic performance in applications.

[0189] Embodiments disclosed herein may utilize circuitry in order to implement technologies and methodologies described herein, operatively connect two or more components, generate information, determine operation conditions, control an appliance, device, or method, and / or the like. Circuitry of any type can be used. In an embodiment, circuitry includes, among other things, one or more computing devices such as a processor (e.g., a microprocessor), a central processing unit (CPU), a digital signal processor (DSP), an application-specific integrated circuit (ASIC), a field-programmable gate array (FPGA), or the like, or any combinations thereof, and can include discrete digital or analog circuit elements or electronics, or combinations thereof.

[0190] An embodiment includes one or more data stores that, for example, store instructions or data. Non-limiting examples of one or more data stores include volatile memory (e.g., Random Access memory (RAM), Dynamic Random Access memory (DRAM), or the like), non-volatile memory (e.g., Read-Only memory (ROM), Electrically Erasable Programmable Read-Only memory (EEPROM), Compact Disc Read-Only memory (CD-ROM), or the like), persistent memory, or the like. Further non-limiting examples of one or more data stores include Erasable Programmable Read-Only memory (EPROM), flash memory, or the like. The one or more data stores can be connected to, for example, one or more computing devices by one or more instructions, data, or power buses.

[0191] In an embodiment, circuitry includes a computer-readable media drive or memory slot configured to accept signal-bearing medium (e.g., computer-readable memory media, computer-readable recording media, or the like). In an embodiment, a program for causing a system to execute any of the disclosed methods can be stored on, for example, a computer-readable recording medium (CRMM), a signal-bearing medium, or the like. Nonlimiting examples of signal-bearing media include a recordable type medium such as any form of flash memory, magnetic tape, floppy disk, a hard disk drive, a Compact Disc (CD),a Digital Video Disk (DVD), Blu-Ray Disc, a digital tape, a computer memory, or the like, as well as transmission type medium such as a digital and / or an analog communication medium (e.g., a fiber optic cable, a waveguide, a wired communications link, a wireless communication link (e.g., transmitter, receiver, transceiver, transmission logic, reception logic, etc.). Further non-limiting examples of signal-bearing media include, but are not limited to, DVD-ROM, DVD-RAM, DVD+RW, DVD-RW, DVD-R, DVD+R, CD-ROM, Super Audio CD, CD-R, CD+R, CD+RW, CD-RW, Video Compact Discs, Super Video Discs, flash memory, magnetic tape, magneto-optic disk, MINIDISC, non-volatile memory card, EEPROM, optical disk, optical storage, RAM, ROM, system memory, web server, or the like.

[0192] Unless stated otherwise, experimental hypotheses or forward-looking models and statements are not intended to be binding on the applicant or exhaustive of the range of possible experimental hypotheses or forward-looking models and statements, but rather are intended to be illustrative, non-limiting examples for aiding those in the art in the understanding and practice of elements of the disclosure.

[0193] As used herein and unless otherwise indicated, the terms “a” and “an” are taken to mean “one”, “at least one” or “one or more”. Unless otherwise required by context, singular terms used herein shall include pluralities and plural terms shall include the singular.

[0194] Unless the context clearly requires otherwise, throughout the description and the claims, the words “comprise”, “comprising”, and the like are to be construed in an inclusive sense as opposed to an exclusive or exhaustive sense; that is to say, in the sense of “including, but not limited to”.

[0195] Unless the context clearly requires otherwise, the phrase “consisting essentially of’ limits the scope of a claim to the specified materials or steps and those that do not materially affect the basic and novel characteristic(s) of the claim.

[0196] Unless the context clearly requires otherwise, the phrase “consisting of’ excludes any element, step, or ingredient not specified.

[0197] If an element is described or claimed herein such that it “comprises” a feature, that description or claim also includes embodiments wherein the element “consists essentially of’ and embodiments wherein the element “consists of’ the feature, unless something else is specifically stated to the contrary.

[0198] A nucleic acid is a polymer of monomer units or “residues”. The monomer subunits, or residues, of the nucleic acids each contain a nitrogenous base (i.e., nucleobase), a five-carbon sugar, and a phosphate group. The identity of each residue is typically indicated herein with reference to the identity of the nucleobase (or nitrogenous base) structure of each residue. Canonical nucleobases include adenine (A), guanine (G), thymine (T), uracil (U) (in RNA instead of thymine (T) residues) and cytosine (C). However, the nucleic acids of the present disclosure can include any modified nucleobase, nucleobase analogs, and / or non-canonical nucleobase, as are well-known in the art. Modifications to the nucleic acid monomers, or residues, encompass any chemical change in the structure of the nucleic acid monomer, or residue, that results in a noncanonical subunit structure. Such chemical changes can result from, for example, epigenetic modifications (such as to genomic DNA or RNA), or damage resulting from radiation, chemical, or other means.

[0199] Unless stated otherwise herein, 1 -letter abbreviations for nucleic acids are consistent with the nomenclature used in the art (i.e., A, Adenine; T, Thymine; C, Cytosine; G, Guanine; U, Uracil). Unless stated otherwise herein, 1-letter abbreviations for amino acids are consistent with the nomenclature used in the art i.e., Alanine, A; Arginine, R; Asparagine, N; Aspartic acid, D; Cysteine, C; Glutamic acid, E; Glutamine, Q; Glycine, G; Histidine H; Isoleucine, I; Leucine, L; Lysine, K; Methionine, M; Phenylalanine, F; Proline, P; Serine, S; Threonine, T; Tryptophan, W; Tyrosine, Y; Valine, V).

[0200] Unless stated otherwise herein, the terms “nucleic acid,” “amino acid,” “nucleotide,” and “peptide” are inclusive and open-ended, and do not exclude from their scope any chemically modified or post-translationally modified versions of these structures, and also do not exclude from their scope any nuclear modified versions, for example, due to the presence of one or more radioisotopes in one or more of these structures.

[0201] The detailed description set forth above in connection with the appended drawings, where like numerals reference like elements, are intended as a description of various embodiments of the present disclosure and are not intended to represent the only embodiments. Each embodiment described in this disclosure is provided as a representative example or illustration and should not be construed as preferred or advantageous over other embodiments. The representative examples provided herein are not intended to be exhaustive or to limit the disclosure to the precise forms disclosed.

[0202] Similarly, any steps described herein may be interchangeable with other steps, or combinations of steps, in order to achieve the same or substantially similar result. Generally, the embodiments disclosed herein are non-limiting, and it is contemplated that other embodiments within the scope of this disclosure may include structures and functionalities from more than one specific embodiment shown in the figures and described in the specification. That is, the present disclosure includes embodiments that combine features from different embodiments.

[0203] In the foregoing description, specific details are set forth to provide a thorough understanding of exemplary embodiments of the present disclosure. It will be apparent to one skilled in the art, however, that the embodiments disclosed herein may be practiced without embodying all the specific details. In some instances, well-known process steps have not been described in detail in order not to unnecessarily obscure various aspects of the present disclosure. Further, it will be appreciated that embodiments of the present disclosure may employ any combination of features described herein.

[0204] In the detailed description herein, references to “one embodiment”, “an embodiment”, “an example embodiment”, “one or more embodiments, etc., indicate that the embodiment described may include a particular feature, structure, or characteristic, but every embodiment may not necessarily include the particular feature, structure, or characteristic. Moreover, such phrases are not necessarily referring to the same embodiment. In addition, when a particular feature, structure, or characteristic is described in connection with an embodiment, it is submitted that it is within the knowledge of one skilled in the art to affect such feature, structure, or characteristic in connection with other embodiments whether or not explicitly described. After reading the description, it will be apparent to one skilled in the relevant art(s) how to implement the disclosure in alternative embodiments. Thus, it will be appreciated that embodiments of the present disclosure may employ any combination of features described herein. All such combinations or subcombinations of features are within the scope of the present disclosure.

[0205] Throughout this specification, terms of art may be used. These terms are to take on their ordinary meaning in the art from which they come, unless specifically defined herein or the context of their use would clearly suggest otherwise.

[0206] The drawings in the FIGURES are not to scale. Similar elements are generally denoted by similar references in the FIGURES. For the purposes of this disclosure, the same or similar elements may bear the same references. Furthermore, thepresence of reference numbers or letters in the drawings cannot be considered limiting, even when such numbers or letters are indicated in the claims.

[0207] In the claims and for purposes of the present disclosure, the terms “a”, “an”, “the”, and the like, refer to the singular and the plural forms of the object or element referenced.

[0208] The present application may include references to directions, such as “vertical,” “horizontal,” “front,” “rear,” “left,” “right,” “top,” and “bottom,” etc. These references, and other similar references in the present application, are intended to assist in helping describe and understand the particular embodiment (such as when the embodiment is positioned for use) and are not intended to limit the present disclosure to these directions or locations.

[0209] The present application may also reference quantities and numbers. Unless specifically stated, such quantities and numbers are not to be considered restrictive, but exemplary of the possible quantities or numbers associated with the present application. Also in this regard, the present application may use the term “plurality” to reference a quantity or number. In this regard, the term “plurality” is meant to be any number that is more than one, for example, two, three, four, five, etc. The term “about,” “approximately,” etc., means plus or minus 5% of the stated value. The term “based upon” means “based at least partially upon.”

[0210] The principles, representative embodiments, and modes of operation of the present disclosure have been described in the foregoing description. However, aspects of the present disclosure, which are intended to be protected, are not to be construed as limited to the particular embodiments disclosed. Further, the embodiments described herein are to be regarded as illustrative rather than restrictive. It will be appreciated that variations and changes may be made by others, and equivalents employed, without departing from the spirit of the present disclosure. Accordingly, it is expressly intended that all such variations, changes, and equivalents fall within the spirit and scope of the present disclosure as claimed.

[0211] While illustrative embodiments have been illustrated and described, it will be appreciated that various changes can be made therein without departing from the spirit and scope of the invention.SEQUENCE LISTINGNON-LIMITING EMBODIMENTS

[0212] While general features of the disclosure are described and shown and particular features of the disclosure are set forth in the claims, the following non-limiting embodiments relate to features, and combinations of features, that are explicitly envisioned as being part of the disclosure. The following non-limiting embodiments contain elements that are modular and can be combined with each other in any number, order, or combination to form a new non-limiting embodiment, which can itself be further combined with other non-limiting embodiments.

[0213] Embodiment 1. A memory system, comprising: a nucleic acid memory device comprising: a nucleic acid molecule comprising a first end and a second end, and further comprising two or more conformations; a first electrically conductive contact coupled to the first end of the nucleic acid molecule; and a second electricallyconductive contact coupled to the second end of the nucleic acid molecule; and a controller operatively coupled to the nucleic acid memory device, the controller including at least one processor and a computer-readable medium having computer-executable instructions stored thereon that, in response to execution by the at least one processor, cause the controller to perform operations including: (i) measuring a first conductance state of the nucleic acid molecule in a first conformation of the two or more conformations, or (ii) measuring a second conductance state of the nucleic acid molecule in a second conformation of the two or more conformations, wherein the first conductance state is associated with a first logic state and the second conductance state is associated with a second logic state.

[0214] Embodiment 2. The memory system of Embodiment 1, wherein the memory system further comprises a stressing device configured to manipulate a conformation of the nucleic acid molecule; and a controller operatively coupled to the stressing device, the controller including at least one processor and a computer-readable medium having computer-executable instructions stored thereon that, in response to execution by the at least one processor, cause the controller to perform operations including: manipulating, with the stressing device, the conformation of the nucleic acid molecule from the first conformation to the second conformation, or from the second conformation to the first conformation.

[0215] Embodiment 3. The memory system of any one of Embodiments 1- 2, wherein the nucleic acid molecule is a single-stranded nucleic acid molecule.

[0216] Embodiment 4. The memory system of any one of Embodiments 1- 3, wherein the nucleic acid molecule is a double-stranded nucleic acid molecule.

[0217] Embodiment 5. The memory system of any one of Embodiments 1- 4, wherein the nucleic acid molecule is an RNA molecule.

[0218] Embodiment 6. The memory system of any one of Embodiments 1- 5, wherein the nucleic acid molecule is a DNA molecule.

[0219] Embodiment 7. The memory system of any one of Embodiments 1- 6, wherein the nucleic acid molecule comprises between 2 and about 100 base pairs.

[0220] Embodiment 8. The memory system of any one of Embodiments 1- 7, wherein the nucleic acid molecule comprises between about 5 and about 50 base pairs.

[0221] Embodiment 9. The memory system of any one of Embodiments 1- 8, wherein the nucleic acid molecule comprises between about 10 and about 25 base pairs.

[0222] Embodiment 10. The memory system of any one of Embodiments 1- 9, wherein the nucleic acid molecule comprises about 10 base pairs.

[0223] Embodiment 11. The memory system of any one of Embodiments 1- 10, wherein the stressing device is configured to adjust a pH of a solution comprising the nucleic acid molecule.

[0224] Embodiment 12. The memory system of any one of Embodiments 1- 11, wherein the stressing device is configured to adjust a salt concentration of a solution comprising the nucleic acid molecule.

[0225] Embodiment 13. The memory system of any one of Embodiments 1- 12, wherein the stressing device is a mechanical strain-inducing device configured to manipulate the conformation of the nucleic acid molecule.

[0226] Embodiment 14. The memory system of any one of Embodiments 1- 13, wherein the mechanical strain-inducing device is selected from the group consisting of optical tweezers, magnetic tweezers, a piezoelectric device coupled to the first or second electrically conductive contact, and a combination thereof.

[0227] Embodiment 15. The memory system of any one of Embodiments 1- 14, wherein the stressing device is an electric field generating device configured to apply an electric field to the first or second electrically conductive contact, thereby inducing a change in conformation in the nucleic acid molecule.

[0228] Embodiment 16. The memory system of any one of Embodiments 1- 15, wherein the first electrically conductive contact and second electrically conductive contact each comprise quasi-one-dimensional semiconducting wires.

[0229] Embodiment 17. The memory system of any one of Embodiments 1- 16, wherein the first electrically conductive contact is selected from the group consisting of a carbon nanotube, a doped boron nitride nanotube, a graphene nanoribbon, a metal nanowire, a doped semiconducting nanowire, and a metallo-intercalated DNA strand.

[0230] Embodiment 18. The memory system of any one of Embodiments 1- 17, wherein the second electrically conductive contact is selected from the group consisting of a carbon nanotube, a doped boron nitride nanotube, a graphene nanoribbon, a metal nanowire, a doped semiconducting nanowire, and a metallo-intercalated DNA strand.

[0231] Embodiment 19. The memory system of any one of Embodiments 1- 18, wherein the first conductance is different from the second conductance.

[0232] Embodiment 20. The memory system of any one of Embodiments 1- 19, wherein a conductance of the nucleic acid in a substantially folded conformation is larger in magnitude than a conductance of the nucleic acid when it is in a substantially unfolded conformation.

[0233] Embodiment 21. The memory system of any one of Embodiments 1- 20, wherein a conductance of the nucleic acid in a substantially folded conformation is smaller in magnitude than a conductance of the nucleic acid when it is in a substantially unfolded conformation.

[0234] Embodiment 22. The memory system of any one of Embodiments 1- 21, wherein the first conductance state of the nucleic acid and the second conductance state of the nucleic acid strand are different by a factor of between about 10 to about 10000.

[0235] Embodiment 23. The memory system of any one of Embodiments 1- 22, wherein the first conductance state of the nucleic acid and the second conductance state of the nucleic acid strand are different by a factor of between about 100 to about 1000.

[0236] Embodiment 24. The memory system of any one of Embodiments 1- 23, wherein the nucleic acid memory device is a first nucleic acid memory device, the memory system further comprising a second nucleic acid memory device comprising: a second nucleic acid molecule comprising a first end and a second end, and further comprising two or more conformations; a first electrically conductive contact coupled to a first end of the second nucleic acid molecule; and a second electrically conductive contact coupled to a second end of the second nucleic acid molecule.

[0237] Embodiment 25. The memory system of any one of Embodiments 1- 24, wherein the logic state is a first logic state, and wherein the computer-executable instructions stored thereon the controller, in response to execution by the at least one processor, cause the controller to perform operations including: measuring a second logic state of the second nucleic acid molecule by either (i) measuring a first conductance of the second nucleic acid molecule in a first conformation of the two or more conformations, or (ii) measuring a second conductance of the second nucleic acid molecule in a second conformation of the two or more conformations.

[0238] Embodiment 26. A nucleic acid memory array, comprising: a first nucleic acid memory device comprising: a first nucleic acid molecule comprising a first end and a second end, and further comprising two or more conformations; a first electrically conductive contact coupled to a first end of the first nucleic acid molecule; and a secondelectrically conductive contact coupled to a second end of the first nucleic acid molecule; a second nucleic acid memory device comprising: a second nucleic acid molecule comprising a first end and a second end, and further comprising two or more conformations; a first electrically conductive contact coupled to a first end of the second nucleic acid molecule; and a second electrically conductive contact coupled to a second end of the second nucleic acid molecule; and a controller operatively coupled to the first nucleic acid memory device and to the second nucleic acid memory device, the controller including at least one processor and a computer-readable medium having computerexecutable instructions stored thereon that, in response to execution by the at least one processor, cause the controller to perform operations including: measuring a first logic state of the first nucleic acid molecule by either (i) measuring a first conductance of the first nucleic acid molecule in a first conformation of the two or more conformations, or (ii) measuring a second conductance of the first nucleic acid molecule in a second conformation of the two or more conformations; and measuring a second logic state of the second nucleic acid molecule by either (i) measuring a first conductance of the second nucleic acid molecule in a first conformation of the two or more conformations, or (ii) measuring a second conductance of the second nucleic acid molecule in a second conformation of the two or more conformations.

[0239] Embodiment 27. The nucleic acid memory array of Embodiments 26, further comprising: a stressing device configured to independently manipulate a conformation of the first nucleic acid molecule and the second nucleic acid molecule; and a controller operatively coupled to the stressing device, the controller including at least one processor and a computer-readable medium having computer-executable instructions stored thereon that, in response to execution by the at least one processor, cause the controller to perform operations including: manipulating, with the stressing device, the conformation of the first nucleic acid molecule from the first conformation to the second conformation, or from the second conformation to the first conformation; and manipulating, with the stressing device, the conformation of the second nucleic acid molecule from the first conformation to the second conformation, or from the second conformation to the first conformation.

[0240] Embodiment 28. A method comprising: storing logic data in a nucleic acid memory system by modulating a conformation of a nucleic acid molecule therein between (i) a first conformation and a second conformation, or (ii) the second conformationand the first conformation, the nucleic acid memory system comprising: the nucleic acid molecule, comprising a first end and a second end; a first electrically conductive contact coupled to a first end of the nucleic acid molecule; and a second electrically conductive contact coupled to a second end of the nucleic acid molecule; and retrieving the logic data from the nucleic acid memory system by measuring, with a conductance measurement device coupled to the first and second ends of the nucleic acid molecule, a conductance value across the nucleic acid molecule.

[0241] Embodiment 29. A non-transitory machine-readable storage medium having instructions stored thereon, which when executed by a processing system, cause the processing system to perform a method comprising: storing logic data in a nucleic acid memory system by modulating a conformation of a nucleic acid molecule therein between (i) a first conformation and a second conformation, or (ii) the second conformation and the first conformation, the nucleic acid memory system comprising: the nucleic acid molecule, comprising a first end and a second end; a first electrically conductive contact coupled to a first end of the nucleic acid molecule; and a second electrically conductive contact coupled to a second end of the nucleic acid molecule; and retrieving the logic data from the nucleic acid memory system by measuring, with a conductance measurement device coupled to the first and second ends of the nucleic acid molecule, a conductance value across the nucleic acid molecule.

Claims

CLAIMSThe embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows:

1. A memory system, comprising:a nucleic acid memory device comprising:a nucleic acid molecule comprising a first end and a second end, and further comprising two or more conformations;a first electrically conductive contact coupled to the first end of the nucleic acid molecule; anda second electrically conductive contact coupled to the second end of the nucleic acid molecule; anda controller operatively coupled to the nucleic acid memory device, the controller including at least one processor and a computer-readable medium having computerexecutable instructions stored thereon that, in response to execution by the at least one processor, cause the controller to perform operations including:(i) measuring a first conductance state of the nucleic acid molecule in a first conformation of the two or more conformations, or(ii) measuring a second conductance state of the nucleic acid molecule in a second conformation of the two or more conformations,wherein the first conductance state is associated with a first logic state and the second conductance state is associated with a second logic state.

2. The memory system of claim 1, further comprising:a stressing device configured to manipulate a conformation of the nucleic acid molecule; anda controller operatively coupled to the stressing device, the controller including at least one processor and a computer-readable medium having computer-executable instructions stored thereon that, in response to execution by the at least one processor, cause the controller to perform operations including:manipulating, with the stressing device, the conformation of the nucleic acid molecule from the first conformation to the second conformation, or from the second conformation to the first conformation.

3. The memory system of claim 1, wherein the nucleic acid molecule is a single-stranded nucleic acid molecule.

4. The memory system of claim 1, wherein the nucleic acid molecule is a double-stranded nucleic acid molecule.

5. The memory system of claim 1, wherein the nucleic acid molecule is an RNA molecule.

6. The memory system of claim 1, wherein the nucleic acid molecule is a DNA molecule.

7. The memory system of claim 1, wherein the nucleic acid molecule comprises between 2 and about 100 base pairs.

8. The memory system of claim 1, wherein the nucleic acid molecule comprises between about 10 and about 25 base pairs.

9. The memory system of claim 2, wherein the stressing device is configured to adjust a pH of a solution comprising the nucleic acid molecule.

10. The memory system of claim 2, wherein the stressing device is configured to adjust a salt concentration of a solution comprising the nucleic acid molecule.

11. The memory system of claim 2, wherein the stressing device is a mechanical strain-inducing device configured to manipulate the conformation of the nucleic acid molecule.

12. The memory system of claim 11, wherein the mechanical strain-inducing device is selected from the group consisting of optical tweezers, magnetic tweezers, a piezoelectric device coupled to the first or second electrically conductive contact, and a combination thereof.

13. The memory system of claim 2, wherein the stressing device is an electric field generating device configured to apply an electric field to the first or second electrically conductive contact, thereby inducing a change in conformation in the nucleic acid molecule.

14. The memory system of claim 1, wherein the first electrically conductive contact and second electrically conductive contact each comprise quasi-one-dimensional semiconducting wires.

15. The memory system of claim 14, wherein the first electrically conductive contact is selected from the group consisting of a carbon nanotube, a doped boron nitride nanotube, a graphene nanoribbon, a metal nanowire, a doped semiconducting nanowire, and a metallo-intercalated DNA strand.

16. The memory system of claim 14, wherein the second electrically conductive contact is selected from the group consisting of a carbon nanotube, a doped boron nitride nanotube, a graphene nanoribbon, and a metallo-intercalated DNA strand.

17. The memory system of claim 1, wherein the nucleic acid memory device is a first nucleic acid memory device, the memory system further comprising a second nucleic acid memory device comprising:a second nucleic acid molecule comprising a first end and a second end, and further comprising two or more conformations;a first electrically conductive contact coupled to a first end of the second nucleic acid molecule; anda second electrically conductive contact coupled to a second end of the second nucleic acid molecule.

18. A nucleic acid memory array, comprising:a first nucleic acid memory device comprising:a first nucleic acid molecule comprising a first end and a second end, and further comprising two or more conformations;a first electrically conductive contact coupled to a first end of the first nucleic acid molecule; anda second electrically conductive contact coupled to a second end of the first nucleic acid molecule;a second nucleic acid memory device comprising:a second nucleic acid molecule comprising a first end and a second end, and further comprising two or more conformations;a first electrically conductive contact coupled to a first end of the second nucleic acid molecule; anda second electrically conductive contact coupled to a second end of the second nucleic acid molecule; anda controller operatively coupled to the first nucleic acid memory device and to the second nucleic acid memory device, the controller including at least one processor and a computer-readable medium having computer-executable instructions stored thereon that, in response to execution by the at least one processor, cause the controller to perform operations including:measuring a first logic state of the first nucleic acid molecule by either (i) measuring a first conductance of the first nucleic acid molecule in a first conformation of the two or more conformations, or (ii) measuring a second conductance of the first nucleic acid molecule in a second conformation of the two or more conformations; and measuring a second logic state of the second nucleic acid molecule by either (i) measuring a first conductance of the second nucleic acid molecule in a first conformation of the two or more conformations, or (ii) measuring a second conductance of the second nucleic acid molecule in a second conformation of the two or more conformations.

19. The nucleic acid memory array of claim 18, further comprising:a stressing device configured to independently manipulate a conformation of the first nucleic acid molecule and the second nucleic acid molecule; anda controller operatively coupled to the stressing device, the controller including at least one processor and a computer-readable medium having computer-executable instructions stored thereon that, in response to execution by the at least one processor, cause the controller to perform operations including:manipulating, with the stressing device, the conformation of the first nucleic acid molecule from the first conformation to the second conformation, or from the second conformation to the first conformation; andmanipulating, with the stressing device, the conformation of the second nucleic acid molecule from the first conformation to the second conformation, or from the second conformation to the first conformation.

20. A method comprising:storing logic data in a nucleic acid memory system by modulating a conformation of a nucleic acid molecule therein between (i) a first conformation and a second conformation, or (ii) the second conformation and the first conformation, the nucleic acid memory system comprising:the nucleic acid molecule, comprising a first end and a second end;a first electrically conductive contact coupled to a first end of the nucleic acid molecule; anda second electrically conductive contact coupled to a second end of the nucleic acid molecule; andretrieving the logic data from the nucleic acid memory system by measuring, with a conductance measurement device coupled to the first and second ends of the nucleic acid molecule, a conductance value across the nucleic acid molecule.

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